Cohort 1 (NSCLC cohort) \r\n* Ability to undergo a fresh tumor biopsy for the purpose of screening for this clinical trial (including able and willing to give valid written consent) to ability or to provide an available archival tumor sample taken less than 3 months prior to study enrollment (and not obtained prior to progression on a PD-1/PD-L1 inhibitor) if a fresh tumor biopsy is not feasible with an acceptable clinical risk; tumor lesions used for fresh biopsies should be the same lesions to be irradiated when possible and should not be the same lesions used as Response Evaluation Criteria in Solid Tumors (RECIST) target lesions, unless there are no other lesions accessible; additional, optional archival tumor tissue is also requested from before the prior PD-1 directed therapy
Cohort 2 (colorectal cohort) \r\n* Ability to undergo a fresh tumor biopsy for the purpose of screening for this clinical trial (including able and willing to give valid written consent) to ability or to provide an available archival tumor sample taken less than 3 months prior to study enrollment if a fresh tumor biopsy is not feasible with an acceptable clinical risk; tumor lesions used for fresh biopsies should be the same lesions to be irradiated when possible and should not be the same lesions used as RECIST target lesions, unless there are no other lesions accessible \r\n* Microsatellite stable (MSS) tumor as documented by either: \r\n** Immunohistochemistry (IHC) testing that does not suggest loss of MLH-1, MSH-2, PMS2 or MSH6 \r\n** Polymerase chain reaction (PCR) testing that does not suggest microsatellite instability (MSI)
Patients with ? 3 visceral metastases (excluding pulmonary lesions), with no lesions >3.0 cm. Patients with substantial tumor burden of non-measurable disease may not be good candidates for an immunotherapy and should be discussed with the Medical Monitor.
Injected lesions (up to two) must be between 20 mm and 90 mm in diameter for IT injection; lesions must be accessible for baseline and on-treatment biopsies.
Have at least 1 site of disease measurable by RECIST v1.1 that has not been treated with local therapy within 6 months of study treatment. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Indication A only: at least 2 measurable lesions as defined per modified RECIST 1.1 within 28 days prior to the first dose of AMG 757
Participants with brainstem lesions
Lesions suspected to be at higher-risk for bleeding such as bowel involvement with tumor that invades into the bowel wall or involves the intraluminal component of bowel by imaging or direct visualization or central pulmonary lesions
Ulcerated skin lesions
Patients with untreated brainstem metastases are eligible if lesions are small and asymptomatic
Measurable Disease Progression: >20% increase in the sum of diameters of measurable lesions from the time of maximal regression or appearance of one or more new lesions.
Pulmonary metastases found at relapse (does not have to be first relapse); no more than 3 lesions per hemi-thorax will be treated but other lesions in the lung may be present
Patients with multiple lesions will be eligible as long as there are no overlapping fields of radiation, including at various time frames
Patients whose disease has progressed following at least 3 cycles of neoadjuvant chemotherapy as defined by at least one of the following:\r\n* Doubling of serum CA-125 level\r\n* At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions\r\n* Clinical deterioration (worsening ascites, carcinomatous ileus, malignant bowel obstruction, severe hypoalbuminemia, declining performance status)
Patients are stage IV (M1) with any combination of T and N with oligometastatic disease as defined by 5 or fewer total sites of metastatic disease involving 3 or fewer organ systems\r\n* Examples of patients eligible for trial\r\n** T3N2M1 non-small cell lung cancer (NSCLC) with 1 central nervous system (CNS) metastatic lesion, 2 liver lesions, and 1 adrenal lesion.\r\n** T4N1M1 colorectal cancer with 1 liver lesion, 4 bone lesions \r\n** T3N0M1 gastric cancer with 1 supraclavicular lymph node, 2 liver lesions, and 2 CNS lesions
Patients with other fibroblastic lesions or other fibromatoses are NOT eligible.
Radiation to all target lesions within 12 weeks of study baseline,
No measurable target lesions.
Presence of metastatic disease that would be amenable to the required biopsies; ideally pre and post biopsies should be from the same lesion and otherwise from lesions in the same organ; if not possible, then biopsy of the lesions in different organs will be permitted
? 3 lesions in the liver
Active oral or genital herpes lesions
Participant must be a candidate for palliative radiation treatment to at least one bone, lymph node, or soft tissue lesion; radiation of visceral lesions (such as lung or hepatic lesions) is not permitted
Participants with bone lesions requiring surgical fixation to provide mechanical stability are ineligible; participants with previously fixed lesions are allowed
MK-1454 (cut/subcut lesions) and MK-1454+pembro (cut/subcut lesions) Arms:
Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > 1.5 cm is acceptable; lesions that are considered non-measurable include the following:\r\n* Bone lesions (lesions if present should be noted)\r\n* Ascites\r\n* Pleural/pericardial effusion\r\n* Lymphangitis cutis/pulmonis\r\n* Bone marrow (involvement by lymphoma should be noted)
The presence of 3 or more MR Visible lesions positive on biopsy.
Radiotherapy delivered to non-target lesions within one week prior to starting study treatment or delivered to target lesions that will be followed on the study (note: prior sites of radiation will be recorded).
Subjects with CNS lesions are excluded
Radiotherapy: at least 3 weeks since most recent radiotherapy; prior radiated lesions will not be evaluable unless there is documented progression post therapy; palliative radiotherapy to localized painful lesions is acceptable when the patient is on study: at least one week after completion of radiation therapy (RT) and recovery from associated toxicities before restarting ARQ 761; irradiated lesions will not be evaluable for response
The PN must be inoperable, defined as a PN that cannot be surgically completely removed without risk for substantial morbidity due to: encasement of or close proximity to vital structures, invasiveness, or high vascularity of the PN; the PN either causes morbidity or it is growing and has the potential to cause morbidity such as (but not limited to): head and neck lesions that could compromise the airway or great vessels, paraspinal lesions that can cause myelopathy, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or are significantly disfiguring, and lesions of the extremity that cause limb hypertrophy or loss of function or pain; PN growth will be defined as a >= 20% increase in PN volume within approximately 3 years prior to enrollment on this trial
Patients with high-grade cervical intraepithelial lesions (CIN2/3) confirmed by colposcopy and biopsy
Presence of brainstem lesions or lesions that are less than 5 mm from the hypophysis or cranial nerves
Patients with multifocal tumors must have resectable lesions
Structurally unstable bone lesions suggesting impending fracture
Patients who have received prior radiation of osseous lesions
Two or more bone lesions
Have a target lesion/s deemed suitable by the treating physicians for stereotactic body radiation therapy (SBRT) with the intent of palliation or prevention of symptoms; this lesion must be: a) 1-3 non overlapping sites in the H&N region OR  b) metastatic lesions outside the head and neck (H&N) region in the lung or bone (a minimum of 1 and a maximum 5 lesions will be irradiated), provided there is no significant overlap between the lesions; patients should have RECIST 1.1 criteria measurable disease in addition to the lesion/s treated with SBRT; if the site/s of SBRT were previously radiated to > 50Gy, there should be > 6 month time interval between the last dose of radiation and the start of SBRT
Have evaluable disease; lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
Patients will be excluded from randomization if they meet any of the following criteria:\r\n* Any of the exclusion criteria; \r\n* Complete response to osimertinib or prior treatment to all visible lesions, such that no lesion is amenable to LCT. Note that patients can receive palliative radiation therapy prior to randomization to CNS lesions or those requiring urgent treatment (e.g. for pain or bleeding), but are only eligible for the study if they have one site amenable to further radiation therapy. In addition, these lesions will be counted towards the total number of metastases, and will also be counted as target lesions
Lesions of any surface span as long as =< 1 cm in maximal height measured from the skin surface for which local control is desired are eligible; a single patient may have multiple eligible lesions that are individually enrolled for the study.
Lesions with a height > 1 cm measured from the skin surface are not eligible for this protocol.
Have measurable disease based on RECIST 1.1 as assessed by the investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Subjects must have a minimum of three (3) evaluable, discrete lesions.
Anal HSIL lesions are visible at randomization and no lesions are suspicious for invasive cancer
Patients requiring palliative radiotherapy to lesions that are defined as target lesions by RECIST criteria at the time of study entry.
Up to 4 metastatic lesions: \r\n* Must have at least 1 bone lesion AND each non-visceral lesion should be less than 5 cm\r\n* Visceral lesions will be limited to one lung lesion (< 2 cm); no liver lesions allowed
Two lesions can be in close proximity (i.e. within 5 cm of each other) if they meet radiation SBRT normal tissue toxicity requirements
Structurally unstable bone lesions suggesting impending fracture
Minimum of 3 radiographically apparent lesions such that there is:\r\n* Minimum of one lesion in areas that have not been previously irradiated that is considered measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria AND\r\n* Minimum of two lesions in areas that have not been previously irradiated that are determined by interventional radiology to be of a size and in a location that a single probe could ablate at least 75% of the lesion; Note: Hepatic lesions measuring =< 3 cm may be treated, as determined by interventional radiology; Note: Brain metastases are not acceptable as lesions defining measurable disease, nor are they candidate lesions for cryoablation
Have measurable disease based on RECIST 1.1 as determined by the investigator/radiology assessment; target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
Presence of a candidate treatment lesion (subcutaneous or nodal lesions are preferable but visceral lesions will be considered) accessible and safe for radiotherapy and serial intralesional injections
Patients must have evaluable disease by clinical exam (i.e. palpable lymphadenopathy, measurable skin lesions, etc.), laboratory assessment (i.e. lymphoma involvement of bone marrow or peripheral blood by morphology, cytology or flow cytometry), and/or imaging (measurable lymph nodes or masses on computed tomography [CT] or magnetic resonance imaging [MRI] and/or evaluable fludeoxyglucose [FDG]-avid lesions on positron emission tomography [PET])\r\n* NOTE: lesions that have been irradiated cannot be included in the tumor assessment unless unequivocal tumor progression has been documented in these lesions after radiation therapy
For Arms A-F, subjects must have biopsiable disease. For Arms A, B, and C, subjects must have at least two lesions amenable to biopsy and response evaluation. For Arms D, E, and F, subjects must have at least three lesions amenable to biopsy, response evaluation, and radiation. Tumor lesions used for biopsy should not be lesions used as RECIST target lesions.
Pathological or clinical (i.e., by imaging) diagnosis of brain metastatic tumor lesions
Total volume of lesions =< 30 cm^3
Presence of unreachable (e.g. located in a region that cannot be reached by needle) or untreatable tumor lesions so that the benefit from the treatment of the treatable lesions does not justify patient's inclusion
Subjects must have at least 1 injectable cutaneous, subcutaneous soft tissue or nodal lesion >= 10 mm in longest diameter; of note, bone lesions are not eligible for injection unless there is a soft tissue component that is amenable to injection; injectable lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment
Patient must have at least 3 measurable lesions that are >= 1.5 cm in one dimension; one of the lesions must be >= 2.0 cm and is amenable to image-guided cryoablation and multiple vaccine injections as determined by interventional radiology and principal investigator (PI) (including tumors that can be safely accessed using imaging guidance and treated with minimal risk to adjacent structures)
Patients must have measurable or non-measurable disease\r\n* Measurable disease\r\n** For visceral or extra-nodal lesions to be considered measurable, they must be >= 10 mm in one dimension, using spiral computed tomography (CT)\r\n** For lymph nodes to be considered measureable (i.e., target or evaluable lesions), they must be >= 20 mm in at least one dimension, using spiral CT\r\n* Non-measurable disease\r\n** All other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions.\r\n*** Lesions that are considered non-measurable include bone lesions (only)
Soft tissue disease progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study); in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm; (Note: the appearance of one or more new non-osseous lesions is also considered progression); clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules, palpable lymph nodes) and at least 10 mm in diameter as assessed using calipers (e.g., skin nodules)\r\n* Per Prostate Cancer Working Group 2 (PCWG2): Visceral (lung, liver adrenal) or extranodal lesions need to be >= 10 mm in one dimension, using spiral CT; however, lymph nodes need to be >= 20 mm in at least one dimension to be considered new
No structurally unstable bone lesions suggesting impending fracture
Radiation within 6 weeks of leukapheresis. Subjects must have progressive disease in irradiated lesions or have additional non-irradiated, PET-positive lesions to be eligible. Radiation to a single lesion, if additional non-irradiated PET-positive lesions are present, is allowed up to 2 weeks prior to leukapheresis.
Subjects must have plexiform neurofibroma(s) that are progressive OR are causing significant morbidity, such as (but not limited to) head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing major deformity (e.g., orbital lesions) or are significantly disfiguring, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions; patients with paraspinal plexiform neurofibromas will be eligible for this trial; histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a plexiform neurofibroma is clinically suspected
No more than 10 lesions in the liver
Any radiation to the target lesions within 6 months of enrollment
Target lesions greater than 10 cm
Have measurable disease based on RECIST 1.1 as confirmed by the blinded MD Anderson radiology; target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions; Note: the same image acquisition and processing parameters should be used throughout the study for a given subject
Patient must have at least one measurable untreated lesion as per modified RECIST criteria; measurable disease may include extrahepatic lesions; abdominal imaging should employ a “liver protocol” image capture technique; the following are not considered measurable lesions: bone lesions, ascites, and pleural effusions; prior radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), or transarterial chemoembolization (TACE) of non-target lesions is allowed
Subjects with PE lesions only in the sub-segmental or smaller arteries;
Have measurable disease based on RECIST 1.1; target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
Target lesions that have previously received radiation must have shown radiographic progression following radiation or must have other non-radiated lesions present
=< 3 liver lesions
Willingness to provide consent for biopsy samples; tumor biopsies will be required for all subjects, tumor lesions used for biopsy should not be lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy; if a RECIST target lesion is used for biopsy the lesion must be >= 2 cm in longest diameter
Patients must have substantial cutaneous neurofibroma burden causing distress to the patient by disfigurement or itching; patients must have >= 9 measurable cutaneous neurofibromas; for the purpose of this study measurability will be defined for each of the lesions selected as target lesions as a neurofibroma with a longest diameter >= 4 mm in the longest diameter
Patients must have multiple tumor lesions (at least 2): one for the ablation procedure and another for evaluation located outside the proposal ablation zone
Five or more metastatic brain lesions
3 or fewer brain metastases; Note: if lesions are symptomatic or greater than or equal to 1 cm each, these lesions must have been treated and stable for 3 months for the patient to be eligible
Have measurable disease based on RECIST 1.1; only cohort 9 and 10 can have evaluable disease (non-measureable lesions); tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions; patients may have bone metastatic disease evaluable according to tumor evaluation criteria best suitable and accepted for the tumor type evaluated
Have biopsiable disease; subjects must have at least one lesion amenable to biopsy; tumor lesions used for biopsy should not be lesions used as RECIST target lesions; in cohort 9: paraganglioma-pheochromocytoma or cohort 10, where there is prominent bony disease, biopsies may not be possible due to the nature of the disease
Lesions located outside of the spinal segments of T2 to T12
Have at least one site of metastatic disease amenable to radiation; all lesions amenable to radiation may be irradiated at the discretion of treating radiation oncologist, depending on the location, size and number of lesions
Patients receiving any other investigational agents for any reason or non-investigational agents administered for the purpose of controlling cancer growth (use of conventional external beam radiation therapy will be allowed during protocol therapy solely for palliation of localized painful lesions or bone lesions at risk of fracture provided the radiation field does not encompass any selected target lesions required for assessment)
Patients may have either metastatic lesions from another primary site or primary hepatocellular carcinoma; patients with one histologically confirmed metastatic lesion of the liver who are presenting for local therapy for lesions concerning for metastases that cannot or should not be biopsied will also be considered for enrollment on a case by case basis; patients can simultaneously receive treatment for multiple hepatic lesions meeting the prior two requirements, at the discretion of the treating radiation oncologist
Disease that is measurable; this is defined as lesions measuring at least 10 mm on radiologic imaging; for lymph node disease, the lesion must measure at least 15 mm or have been biopsied and shown to contain melanoma; skin or mucosal lesions that are not measurable on radiologic imaging but measure at least 5 mm on clinical exam are also acceptable
Patients must have pathologic diagnosis of adenocarcinoma or large cell carcinoma of the lung with confirmation by immunohistochemistry (e.g., transcription termination factor 1 [TTF-1] positivity) (histologic tissue diagnosis is recommended, but cytology is acceptable); stage IIIA/IIIB or oligometastatic stage IV in which the patient is still considered an appropriate candidate for aggressive chemoradiotherapy for the primary tumor; oligometastatic disease is defined as =< 5 metastatic sites (=< 3 lesions per organ); for intracranial metastasis, the patient should have asymptomatic disease that is stable on steroids or 1 to 3 symptomatic metastatic lesions treated with stereotactic radiosurgery (SRS)
Lesions that are accessible for injection and electroporation, defined as cutaneous or subcutaneous disease.
PHASE II: Presence of at least one measurable CNS target lesion for which the following criteria are met:\r\n* At least 5 mm in size (Note: intra-cranial disease assessments can only be performed using contrast-enhanced magnetic resonance imaging [MRI]; MRI scan slices of 1 mm are necessary for brain metastases between 5 and 10 mm in size)\r\n* Lesions must be untreated or progressive according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (>= 20% increase in longest diameter on baseline scan) after previous local therapy\r\n* Participants who are receiving corticosteroids must be on a stable or decreasing dose for at least 2 weeks prior to the first dose of study treatment\r\n* For patients who have received local therapy to all brain lesions (e.g., whole brain radiation therapy [WBRT]), progression of pre-existing lesions based on RECIST 1.1 (> 20% increase in longest diameter on baseline scan) or new measurable lesions are required
The additional lesions will each be treated with stereotactic radiosurgery
All metastatic lesions must be separated by a minimum of 3 cm as measured from the peripheral edges of the lesions which are in closest proximity to one another; if multiple lesions are present and are not all >= 3 cm away from each other, the patient will be deemed ineligible
Brain lesions with an equivalent diameter of > 40 mm in size on MRI imaging at the time of consultation/screening for protocol eligibility
Recurrent lesions with dimension and contour that are determined by the treating neurosurgeon to be appropriate for MLA
Patients must have non-measurable disease (such as nuclear medicine bone scans) and non-target lesions (such as PSA level) assessed within 28 days prior to initial administration of drug
Patients with intradural or intramedullary lesions, or lesions with < 2 mm distance from tumor to spinal cord
Patients with a history of complete surgical resection of CNS lesions are eligible if there is no evidence of CNS lesions (MRI or CT required) at study entry evaluation and if other entry criteria are met
Radiation within 4 weeks of study enrollment; radiotherapy not permitted while on study; exception: palliative radiotherapy of metastasis in extremities is allowed, but such lesions cannot be used as target or non-target lesions
Patients presenting with lesions that may harbor an occult infectious source
The additional lesions will each be treated with single fraction stereotactic radiosurgery
Patients with ulcerated depressed lesions (as defined by Paris Classification type III)
Lesions not amenable to GTR
Patients will be excluded if they have < 4 lesions, or > 15 lesions at enrollment or > 20 lesions at the time of treatment (note: patients who qualify for enrollment based on having 4-15 lesions, but who are discovered to have up to 20 lesions on the volumetric MRI used for treatment planning will be allowed to continue on study)
Dermatology evaluation with excision of any suspicious lesions prior to initiation of therapy
patients with high grade cervical intraepithelial lesions (CIN2/3)
2. Stage II-IV disease; T 2-4, N any, M0. Measurable disease is required with the following criteria: Measurable lesions can be accurately measured, with at least one diameter >\\= 1.0 cm by spiral CT scan or MRI. Lesions can be bidimensionally measurable or unidimensionally measurable. Every effort should be made to measure lesions in two dimensions. Measurable disease is present if the patient has one or more measurable lesions. Non-measurable lesions/disease are all other lesions, including small lesions (those with measurements < 2.0 cm; or < 1.0 cm with spiral CT).
Presence of any oral lesions that may confound the ability to assess oral mucositis grade
Patients must be eligible to have all lesions treated as determined by the study radiation oncologist.
Bone lesions: lytic lesions, severe osteopenia or pathologic fractures
presence of 3 brain lesions or less
One to 3 painful lesions.
More than 3 painful lesions or more than 2 requiring immediate localized treatment
Presence of ulcerating or fungal skin lesions or infection of the breasts
Concurrent vaginal, vulvar, anal lesions or symptomatic infections
Measurable disease, according to RECIST v1.1. Note that lesions intended to be biopsied should not be target lesions
Non-measurable lesions include the following: small lesions (longest diameter < 1.0 cm for all lesions other than pathologic lymph nodes, which are >= 1.0 cm and < 1.5 cm in the short axis), bone metastases, pleural effusions, pericardial effusions, ascites, inflammatory breast disease, leptomeningeal disease, lymphangitis pulmonis, lymphangitis cutis, and abdominal masses not followed by CT or magnetic resonance imaging (MRI)
Structurally unstable bone lesions suggesting impending fracture
Phase II: inoperable PN causing morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or significant cosmetic problems, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions in patients with NF1; histologic confirmation of PN tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a PN is clinically suspected; a PN is defined as a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches; a spinal PN involves two or more levels with connection between the levels or extending laterally along the nerve; in addition to PN, all study subjects must have either positive genetic testing for NF1 confirmed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory or have at least one other diagnostic criterion for NF1 listed below (National Institutes of Health [NIH] Consensus conference):\r\n* Six or more café-au-lait macules (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects)\r\n* Freckling in axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
Lesions suspected to be at higher-risk for bleeding such as bowel involvement with tumor that invades into the bowel wall or involves the intraluminal component of bowel by imaging or direct visualization or central pulmonary lesions
Ulcerated skin lesions
No prior radiation to lesions being treated
Have measurable disease based on RECIST 1.1., or detectable disease; lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
Soft tissue lesions >= 1.0 cm in longest axis\r\n* Soft tissue lesions < 1.0 cm that have been stable for > 6 months (must not have enlarged > 5 mm) are permitted
Patients must have no evidence of metastatic disease; metastatic disease:\r\n* Are lesions which are discontinuous from the primary tumor, are not regional lymph nodes and do not share a body cavity with the primary tumor; if there is any doubt whether lesions are metastatic, a biopsy of those lesions should be taken\r\n* Skeletal lesions in adjacent bones (trans-articular)\r\n* Contralateral pleural effusion and contralateral pleural nodules\r\n* Distant lymph node involvement\r\n* Patients with pulmonary nodules are considered to have metastatic disease if the patient has:\r\n** Solitary nodule > 0.5 cm or multiple nodules of > 0.3 cm unless biopsied and negative for Ewing's\r\n** Biopsies of solitary nodule =< 0.5 cm or multiple nodules =< 0.3 cm are not required but if performed and positive indicate metastatic disease
Subjects who have received radiotherapy to tumor lesions that would be chosen as target lesions (measurable disease) within 4 weeks before the start of treatment, except if there is objective evidence of progression of the lesion by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between the prior radiotherapy and the screening CT or magnetic resonance imaging (MRI) scan; palliative radiotherapy to non-target lesions is allowed at the investigator’s discretion
Patients having no distinct measurable lesions outside of the field of radiation
Previous treatment of the target lesions with radiation therapy
Patients must have baseline skeletal survey to document lytic lesions, osteopenia or compression fracture within 28 days prior to registration
Participants must have measurable melanoma; measurable disease is defined as at least one lesion that can be measured accurately in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan; cutaneous or subcutaneous lesions may be considered measurable if they can be measured reliably as >= 10 mm by direct physical exam measurement; in addition, participants must also have separate disease, which may or may not be measurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST), but must be readily accessible for core needle biopsy, excisional biopsy, and/or surgical resection; this disease may include one large tumor tissue deposit from which biopsies can be harvested multiple times or may include multiple deposits which can be biopsied, or excised individually, on different dates; please see below for suggested minimum size requirements of tumor tissue to be used for biopsy for research:\r\n* 1 lesion >= 5 cm^3 or\r\n* 2 lesions >= 3 cm^3 each\r\n* 3 lesions >= 2 cm^3each OR\r\n* >= 3 skin lesions, such that the surface area is approximately 1 cm^2 each (or in aggregate for several lesions) and the total volume of tumor is approximately 260-325 mm^3 or greater for each biopsy time point; these subjects will need >= 3 such epidermal/dermal tumor lesions; excisional tumor tissue biopsies will be performed on one or more lesions at each time point; it is acceptable to biopsy more than one lesion, that may be less than 1 cm^2 in surface area, as long as the total tissue removed has a surface area of approximately 1 cm^2 or greater\r\n* A combination of these may be acceptable, as long as there appears to be enough tumor tissue to remove approximately 325 mm^3 or more of tissue at each time point
One to ten brain metastatic lesions
Has evaluable disease as defined as lesions that can be accurately measured at least in one dimension by radiographic examination or physical examination and other lesions such as bone lesions, leptomeningeal disease, ascites, hepatosplenomegaly from disease.
Brain lesions >3 lesions which were previously treated with SRT
Patients must have no lytic lesions on skeletal surveys and no hypercalcemia (i.e., >= 11 mg/dL)
Patients must not have baseline bone lesions or plasmacytomas
Lung tumor lesions with increased likelihood of bleeding;
Tumor biopsies are required. If a subject has inaccessible lesions, such as in ovarian cancer, HCC, or gastric cancer, or highly vascular lesions, such as RCC, enrollment may be considered with medical monitor approval, and archived tissue may be acceptable.
Participants with paraspinal, paratracheal and mediastinal pathologic lesions larger than 2 centimeters unless they are previously irradiated
Bone lesions
Patients must have completed any prior chemotherapy, radiotherapy or major surgery at least 4 weeks before receiving study treatment; ongoing toxicities related to treatment must be =< grade 1 and patients with grade 2 alopecia or peripheral neuropathy can also be included; palliative radiation to < 10% of bone marrow is permissible if completed within one week of commencing study treatment as long as the toxicities secondary to palliative radiotherapy are limited to grade 1; the lesions that have received radiation treatment immediately before will be excluded as target lesions; previously irradiated lesions can be considered as targeted lesions, as long as there is prove of radiological progression
Unidimensionally measurable disease; indicator lesions must not have been irradiated unless they have grown following radiation therapy
Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy [with the exception of palliative bone-directed radiotherapy, or radiotherapy administered on non-target superficial lesions], immune therapy, or cytokine therapy except for erythropoietin). Radiotherapy administered to superficial lesions is not allowed if such lesions are considered target lesions in the efficacy evaluation or may influence the efficacy evaluation of the investigational agent
Subjects must have measurable lesions (at least one target lesion measuring 2 cm in diameter) by computerized tomography (CT) scan, and/or measurable lymphoma cutaneous lesions of any size
Have measurable disease (? 1 measurable lesion) based on RECIST v1.1 as determined by the site study team. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Measurable disease by RECIST 1.1 criteria. Target lesions selected for tumor measurements should be those where surgical resection or radiation are not indicated or anticipated.
A fresh tumor biopsy for the purpose of screening or an available archival tumor sample. Tumor lesions used for fresh biopsies should not be the same lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy.
Soft-tissue progression defined as an increase ? 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions.
Soft-tissue progression defined as an increase ? 20% in the sum of the diameter (SOD; short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD, or the appearance of one or more new lesions, since the onset of the most recent prior therapy
Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable; lesions that are considered non-measurable include the following:\r\n* Bone lesions (lesions if present should be noted)\r\n* Ascites\r\n* Pleural/pericardial effusion\r\n* Lymphangitis cutis/pulmonis\r\n* Bone marrow (involvement by SLL or CLL should be noted)
Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease as defined above.
Patients must have baseline skeletal survey (whole body x-ray) to document lytic lesions, osteopenia or compression fracture
have at least 1 measurable lesion assessable by radiological imaging. Tumor lesions located in a previously irradiated area are considered measureable if progression has been demonstrated in such lesions
Previous use of systemic chemotherapy or other investigational drugs for the treatment of inoperable locally recurrent or metastatic tumors (previous use of radiotherapy or chemotherapy in this setting is not an exclusion criterion if: 1) non-irradiated target tumor lesions are present at randomization for the purpose of tumor response assessment or 2) in the absence of non-irradiated target tumor lesions, progression of the irradiated tumor lesions according to the RECIST criteria version 1.1 is documented)
Presence of at least 2 measurable lesions
Patients with histologically documented metastatic melanoma with at least 3 cutaneous lesions measuring over 5 mm diameter; at least two lesions must be at least 10 mm in diameter to serve as the injected disease; at least one other lesion measuring at least 5 mm in diameter may serve as the non-injected lesion that will be measurable disease; patients will have stage IIIB or IIIC (in-transit lesions with or without nodal metastases) or stage IV M1A disease with cutaneous or nodal lesions assessable for administration of LL37; patients are only eligible if their melanoma deposits are not amenable to complete surgical excision; skin lesions that are 5 mm or greater are deemed measurable however lesions that are at least 10 mm in diameter will be preferentially utilized for LL37 injection
Patients may receive bisphosphonates; however, if used, bone lesions may not be used for progression or response
Patients must have brain imaging by MRI, CT or PET within 30 days prior to lymphodepletion; patients may have asymptomatic brain lesions that are =< 1 cm each, lesions that are > 1 cm that have been irradiated and in the opinion of the investigator no longer represents active disease will also be allowed
Prostate with multiple cystic lesions.
To differentiate T3 lesions involving the mediastinal pleura from T4 lesions involving major vessels or organs, a chest magnetic resonance imaging (MRI) will be obtained; if any uncertainty remains, the patient will have four-dimensional computed tomography (CT) scans (4DCT) in an effort to determine the degree of tumor motion; a freely mobile tumor during ventilation will be judged to be T3 disease
Repeat palliative RT will be permitted for the treatment of isolated, non-target lesions
Lesions that have been radiated previously cannot be considered target lesions
Concurrent radiotherapy is not permitted for disease progression on treatment on protocol; however, symptomatic treatment for pre-existing non-target lesions would be allowed with approval from the principal investigator
Note: Biopsied lesions should not be used as target lesions.
Note: Biopsied lesions should not be used as target lesions.
Patient has 1-3 major painful osseous metastases (target lesions); these do not require biopsy if they are radiographically consistent with osseous metastases; the target lesions may be from any primary cancer or unknown primary cancer, including multiple myeloma
Long bone target lesions with a Mirels fracture score > 7
Subjects must have plexiform neurofibroma(s) that are progressive OR are causing significant morbidity, such as (but not limited to) head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing major deformity (e.g., orbital lesions) or are significantly disfiguring, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions; subjects with paraspinal plexiform neurofibromas will be eligible for this trial; histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a plexiform neurofibroma is clinically suspected
Have at least 1 measurable lesion per RECIST v1.1. Note: Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy. Brain lesions may not be used as target lesions if they were: 1) previously treated with whole brain radiation therapy (WBRT) within 3 months, or 2) previously treated by stereotactic radiosurgery (SRS) or surgical resection.
Patients with more than 6 discrete extra-cranial lesions
No more than 5 lesions
Concurrent radiotherapy is not permitted for disease progression on treatment on protocol, but might be allowed for pre-existing non-target lesions with approval from the principal investigator of the trial
At least one bi-dimensionally measurable nodal lesion > 1.5 cm in its longest diameter by computed tomography (CT) scan or magnetic resonance imaging (MRI), as defined by the Lugano Classification\r\n* Site of disease deemed amenable to low-dose, local radiotherapy (2 x 2Gy) should not be counted as target lesions\r\n* Previously irradiated lesions should not be counted as target lesions\r\n* Lesions that are intended to be used to collect tissue samples for biopsy should not be counted as target lesions\r\n* Bone lesions should not be counted as target lesions
Patients have progressive metastatic disease with predominantly bone metastasis with 1 or more lesions and at least 1 bone lesion has pathological confirmation, have not been treated or have been treated with any prior therapies (including bisphosphonate treatment and/or radiation therapy); patients can have soft tissue involvement (lymph node and skin) and/or metastatic lesions at major organ sites (i.e. lung, liver, etc)
For visceral or extra-nodal lesions to be considered measurable, they must be >= 10 mm in one dimension, using spiral CT
All other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions; lesions that are considered non-measurable include bone lesions (only)
Patients with node only disease (i.e. no presence of visceral, extra nodal lesions or bone lesions) must have node(s) that measure >= 15 mm in short axis
No structurally unstable bone lesions suggesting impending fracture
Patients must have measurable lesions
Patient with symptomatic or growing CNS metastatic lesions
Metastatic disease outside the intraperitoneal cavity and retroperitoneum, intrahepatic lesions, or pleural effusions; significant ascites precluding catheter placement; exception: intrahepatic lesions removed or planning to be removed during the debulking procedure
STEP 1 ENROLLMENT: three or less metastatic lesions (not sites); each lesion (including a satellite nodule) will individually be counted as one, and intrathoracic lymph node involvement (defined here as hilar, mediastinal, or supraclavicular nodes, N1-N3) will collectively be counted as one; in addition, patients can receive treatment to CNS lesions or other symptomatic lesions requiring urgent local therapy prior to randomization, but these lesions will be counted towards the total number after chemotherapy, and patients will only be eligible if there are remaining sites amenable to local therapy after up-front systemic therapy
STEP 2 ENROLLMENT AND RANDOMIZATION: treatment to central nervous system lesions, such as the brain or spine (prior to first line systemic therapy), or symptomatic lesions requiring urgent palliative radiation, is permitted prior to randomization, in which case the patient would be randomized to treatment of other metastatic sites or the primary sites (based on the disease remaining after first-line treatment); these treated lesions should be counted towards the total number of metastases at the time of enrollment
Patients must have disease that is refractory (unresponsive) to radioactive iodine (RAI) treatment as defined by one of the following: \r\n* One or more measurable lesions that do not demonstrate RAI uptake \r\n* One or more measurable lesions progressive by RECIST 1.1 within 12-months of prior RAI therapy and/or the appearance of one or more new lesion within 12 months of prior RAI therapy\r\n* Cumulative RAI dose of > 600 mCi\r\n* Measureable disease that is fludeoxyglucose (18F) positron emission tomography (PET) scan positive
Have measurable skin disease with 1 to 4 eligible baseline target lesions with a total area >= 25 cm^2 but =< 100 cm^2; eligible lesions must be below the neck and may not involve the genitalia, intertriginous areas, internally, or to frankly ulcerated or infected skin
Confirmed presence of somatostatin receptors on all target lesions (for target/non-target/measurable lesions definition see §Appendix 2, Section 1 and 2, RECIST Criteria, Version 1.1) documented by CT/MRI scans, based on positive OctreoScan® imaging within 24 weeks prior to randomization in the study (to be centrally confirmed). The OctreoScan® should be one that was performed while the patient was on a fixed dose of Octreotide LAR. If a patient has had an OctreoScan® performed while Octreotide LAR treatment-naïve, the patient must have a repeat OctreoScan® performed after 3 months of Octreotide LAR treatments before entering the clinical study to prove that the index lesions or new lesions still meet the criteria for inclusion. It is acceptable to have patients temporarily switched to Octreotide s.c. (up to six weeks) in order to obtain an OctreoScan®, provided they return to the same fixed dose of Octreotide LAR prior to the scan.
Non-measurable disease: all other lesions, including small lesions (less than 1.0 x 1.0 cm) and truly non-measurable lesions; lesions that are considered non-measurable include the following:\r\n* Bone lesions (lesions if present should be noted)\r\n* Ascites\r\n* Pleural/pericardial effusion\r\n* Lymphangitis cutis/pulmonis\r\n* Bone marrow (involvement by Hodgkin’s lymphoma should be noted)
Lesions must be amenable to accurate and repeat measurement.
Subjects with benign lesions such as fibroadenoma, atypical ductal hyperplasia, sclerosing adenosis, Papilloma, fibrocystic disease of breast
Subjects must have measurable or evaluable disease; disease sites that are evaluable for progression but not measurable per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1 include:\r\n* Bone lesions\r\n* Previously irradiated lesions\r\n* Cutaneous manifestations (non-discrete lesions only)
Previous treatment with radiotherapy to the target lesions
All patients must be considered an eligible candidate for systemic therapy as determined by the investigator; to be eligible, LYP patients must be in need of systemic therapy i.e., have scarring or active lesions (>= 10 per month), or any number of active lesions on face, hands, or feet
At least 1 target lesion, as defined by RECIST, that has not been irradiated; new lesions that have developed in a previously irradiated field may be used as sites of measurable disease assuming all other criteria are met; all target lesions must have a unidimensional diameter of at least 1 cm for spiral computed tomography (CT) scans if the reconstruction algorithm is 0.5 cm, or a standard uptake value (SUV) >= 2.5; baseline measurements/evaluations must be completed within 4 weeks prior to treatment
Disease to be treated on protocol is less than 2 mm from the spinal cord and therefore will not meet dose constraints; Note: patients with eligible and ineligible lesions will be accrued to this protocol; only target eligible lesions will be treated per protocol; other eligible and ineligible lesions will be treated at the discretion of the treating physician
Lesions which comprise > 70% of the width of weight bearing bones, such as the femur
Areas to be treated on protocol do not include metastases to liver, brain or lung; Note: patients with eligible and ineligible lesions will be accrued to this protocol; only target eligible lesions will be treated per protocol; other eligible and ineligible lesions will be treated at the discretion of the treating physician
Patients cannot have more than 3 liver lesions
BONE LESIONS:
Other metastatic lesions not previously treated with radiation therapy are allowed providing they are measurable by CT or MRI
Untreated T1-2N0 primary lesions may also be treated with SBRT
Patients with T1, N0 lesions
CT scans showing involvement of ? 1clearly demarcated lesions measuring ? 1.5 cm
At least 2 biopsiable easily accessible cutaneous and subcutaneous lesions in patients in the metastatic disease cohort
At least one of the following indications for therapy:\r\n* Pulmonary involvement\r\n* Visceral involvement\r\n* Pain\r\n* Edema\r\n* Substantial lymph node involvement\r\n* Ulcerating lesions\r\n* Decreased range of joint motion due to KS\r\n* Multiple lesions not amenable to local therapy\r\n* Significant psychological impact leading to social withdrawal
Patients with neurofibromatosis type 1 (NF1) and an inoperable plexiform neurofibroma that has the potential to cause significant morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or significant cosmetic problems, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions; histologic confirmation of tumor is not required in the presence of consistent clinical and radiographic findings; however, if any clinical observation or scan suggests possible malignant transformation, the tumor should be biopsied prior to therapy; patients without biopsy-proof of a plexiform neurofibroma must have at least one other diagnostic criteria for NF1 as defined by the National Institutes of Health (NIH) Consensus Conference:\t\r\n* Six or more café-au-lait spots (> 0.5 cm in prepubertal subjects or > 1.5 cm in postpubertal subjects)\r\n* Freckling in the axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first degree relative with NF1
Subject must have at least 1 measureable lesion based on RECIST V1.1. Previously irradiated lesions will not be considered as measurable lesions.
Subject has at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1. Evaluable target lesions may not have been treated with local therapy; previously treated lesions may only be evaluated as target lesions if they are the only lesions available and have shown objective definite progression after prior treatment. Local therapy must have been completed at least four weeks prior to baseline tumor evaluation
Radiation therapy (except for localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture): ?4 weeks
Radiation therapy (localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture) ?2 weeks
Brain lesions must be 1) supratentorial, 2) ten lesions or less, and 3) not considered a candidate for surgical resection
For Phase I: Locally advanced or metastatic B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E/K positive melanoma that is either treatment-naïve or treatment-experienced; for the latter, progression, or stable as best response, or intolerance to the last treatment is required; previous treatments can be local or systemic therapies; there are no limits to the number of prior therapies; for all patients, disease does not have to be measurable but must be evaluable, which is defined as one or more lesions which are known to be present, but which cannot be measured; e.g.: bony lesions, pleural effusion, ascites
Patient must have 1 lesion with a maximum AXIAL diameter of 12 cm; up to 3 satellite lesions are permitted; satellite lesions, are defined as lesions less than 2 cm that are within 1 cm of the periphery of the dominant lesion (GTV) are permitted; the satellite lesions are NOT included in the AXIAL diameter measurement; regional lymph node involvement within the porta hepatis (as medial as superior mesenteric vein [SMV] portal vein confluence) is permitted if nodes are deemed clinically positive (i.e. fludeoxyglucose F 18 [FDG] avid)
Multiple lesions that don’t meet the criteria as satellite lesions
Participants must have cutaneous lesion(s) amenable to four total biopsies (either four lesions > 4 mm or one large lesion measuring 20 mm that can undergo serial biopsy) and at least five additional lesions measurable for assessment with no improvement over the four weeks prior to enrollment
KS patients with skin-only disease must have cutaneous lesions amenable to four 3 mm punch biopsies during the course of the study (either four separate lesions measuring >= 4 mm each OR two separate lesions measuring >= 8 mm each)
Preferentially radiologically by tumor growth or new lesions, or by
Participants must have cutaneous lesion(s) amenable to four (4) 5-mm tumor biopsies during the study (either 4 separate lesions measuring >= 5 mm each OR 2 separate lesions measuring >= 10 mm each) and at least five additional lesions measurable for assessment with no improvement over the past month
Patients with single or multiple cerebellar or cerebral cortex lesions are eligible
Diagnosis must be confirmed clinically at baseline with 1-2 lesions having been biopsied no sooner than 2 weeks prior to treatment
Primary lesions may be acceptable for enrollment
Radiation for symptomatic lesions within 14 days of study enrollment
Either complete disappearance of all lesions, or persistence of metastatic disease (stable disease) without unequivocal progression or the occurrence of new lesions
Presence of non-target lesions that have not previously been irradiated or biopsied; to allow for collection of needle-biopsies at Screening and after completion of Kevetrin treatment
Measurable disease, as defined by RECIST v1.1; previously irradiated lesions can be counted as target lesions if clearly progressing after radiation
One or more of the following “risk” criteria for failure with conventional SBRT treatment alone:\r\n* Peripheral tumor >= 4 cm in any dimension\r\n* Central tumor (i.e. gross tumor within 2 cm of a major bronchus/vessel, or heart/pericardium), including hilar lymph node(s)\r\n* Multiple tumors (i.e. satellitosis-defined T3-4, or bilateral synchronous primary lung cancer; note that the maximum number of total lesions allowable on this study for treatment with SBRT is 3 (three), and all lesions must be amenable to SBRT and treated with SBRT on this study; note that it is not necessary for all lesions felt to be malignant to be biopsied
Have measurable disease based on modified severity-weighted assessment tool (mSWAT); tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
Radiotherapy within 14 days before the first dose of either study drug except localized radiation therapy for lytic bone lesions and plasmacytomas
No more than 10 treatable lesions as evaluated by an experienced interventional oncologic radiologist for eligibility and lesion accessibility as the ablation of more than 10 lesions becomes technically infeasible; these lesions must be treated in a two- to three-week time period from initial interventional radiology evaluation; lung and liver lesions can range from 1 cm to 7 cm for a single lesion and no greater than 5 cm for multiple lesions; there are no size criteria for the osseous lesions
The lesions will be amenable to a safe, ultrasound/computed tomographic/fluoroscopic guided percutaneous approach; the targeted metastases must be sufficiently separable from the central nervous system, major peripheral motor nerves, bowel, and bladder; all lesions must be amenable to treatment
Patients may not have received prior systemic or hepatic directed infusional/embolization therapies for advanced uveal melanoma; local therapies such as radiofrequency ablation or cryotherapy for metastatic disease are permitted but must have been performed at least 21 days prior to initiation of study therapy; lesions treated with local modalities such as radiofrequency ablation or cryotherapy may not be used as target lesions unless they demonstrate growth over a minimum of 3 months on subsequent imaging studies
Patients with symptomatic relapse, including those with new bone lesions, soft tissue plasmacytomas, an increase in the size of existing bone lesions or soft tissue plasmacytomas, decrease in hemoglobin, rise in serum creatinine or hypercalcemia
Patients are also considered to have progressive disease when:\r\n* New bone or soft tissue lesions (eg, plasmacytomas) are identified; or\r\n* There is an unequivocal increase in the size of previously existing lesions; or\r\n* The development of an otherwise unexplained serum calcium > 11.5 mg/dL is also a marker of progressive disease (PD)
Participants with multiple basal cell carcinomas, including participants with Gorlin syndrome, with at least 6 clinically evident basal cell carcinomas at the time of randomization, of which 3 measure 5 mm or more in diameter and are considered target lesions. All other lesions are considered to be non-target lesions
Histopathologic confirmation that at least one of the three target lesions is basal cell carcinoma
Structurally unstable bone lesions suggesting impending fracture
2. If lesions are too small to be visualized or palpable for accurate injection.
Presence of more than 50 melanoma lesions
Subjects with NF-1 and only PN lesions that cannot be evaluated by volumetric analysis (only applicable to Part B).
Patients with NF1 and inoperable PN defined as PN that cannot be surgically completely removed without risk for substantial morbidity due to encasement of, or close proximity to vital structures, invasiveness, or high vascularity of the PN; the PN has to cause (stratum 1) or have the potential to cause (stratum 2) significant morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, paraspinal lesions that can cause myelopathy, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or are significantly disfiguring, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions; patients will be enrolled into stratum 1 or 2 based on PN related morbidity; histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a PN is clinically suspected; a PN is defined as a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches; a spinal PN involves two or more levels with connection between the levels or extending laterally along the nerve; in addition to PN, all study subjects must have either positive genetic testing for NF1 or have at least one other diagnostic criterion for NF1 listed below (National Institutes of Health [NIH] Consensus conference):\r\n* Six or more café-au-lait macules (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects)\r\n* Freckling in axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
Radiotherapy delivered to non-target lesions within one week prior to starting study treatment or delivered to target lesions that will be followed on the study (NOTE: prior sites of radiation will be recorded)
Patients must have measurable disease in two dimensions and >= 2 cm is acceptable (or 1.5 cm if 0.5 slices are used, as in spiral computed tomography [CT] scans); lesions that are considered intrinsically non-measurable include the following:\r\n* Bone lesions\r\n* Leptomeningeal disease\r\n* Ascites\r\n* Pleural/pericardial effusion\r\n* Inflammatory breast disease\r\n* Lymphangitis cutis/pulmonis\r\n* Abdominal masses that are not confirmed and followed by imaging techniques\r\n* Cystic lesions\r\n* Lesions that are situated in a previously irradiated area
Measurable lesions are not required for admittance to the study - but are desirable.
Brain lesions with a propensity to bleed
Patients with presence of multiple bladder lesions
Expansion cohorts: Patients with metastatic melanoma with measurable, stage III (in transit lesions) or stage IVA, IVB or IVC disease at least two measurable lesions/tumors
Patients will have from 1 to 5 painful lesions and only the most painful lesion will be treated.
More than 5 painful lesions, or more than 1 requiring immediate localized treatment
Have measurable disease based on modified severity-weighted assessment tool (mSWAT); tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
Patients must, in the opinion of the treating physician, be candidates for intralesional administration into cutaneous, subcutaneous, or nodal lesions; patients must have at least 2 injectable lesions
Patients with lesions to the nasal mucosa
Traumatic lesions/hematomas
T1N0M0 and T2N0M0 glottic lesions
Willingness to have photographs taken to document lesions
Patients with lesions of Gleason 7 or greater outside the planned treatment area.
Prostate with multiple cystic lesions.
Has lesions involving chest wall
Unmeasurable target tumor site by RECIST 1.1 or PRC (example [ex]: lesions < 2 cm on computed tomography [CT] or magnetic resonance [MR] scan, leptomeningeal disease, ascites, pleural/pericardial effusion, lymphangitis, non-fludeoxyglucose [FDG]-avid skin lesions)
Minimum of at least three discrete metastatic lesions in the bone and/or soft tissue amenable to whole body PET imaging per the judgment of study radiologist
Confirmed presence of somatostatin receptors (type 2) on technically evaluable tumour lesions documented by a positive Somatostatin Receptor Scan acquired within 6 months prior to screening (Visit 1) and showing minimally two lesions in at least one of the key organs; these images shall be available to be sent to the imaging core lab electronically to ascertain quality and admissibility
Fewer than five lesions in total and more than 25 lesions/organ detected by the previous somatostatin receptor scan in key organs: liver, lymph nodes, bone or lungs
Participants must present with a gadolinium-enhancing brain lesion (or lesions) that are thought by the neuroradiologist and the neurosurgeon to be consistent with high-grade glioma; these may be newly diagnosed lesions or recurrent tumors
Patients must have MRI findings reporting intraprostatic lesions suspicious for malignancy
Ability to detect lesions within prostate on MRI for biopsy
Has lesions involving chest wall
Patient has:\r\n* Liver lesions that are untreated liver lesions or \r\n* Changing treatment regimen/type and/or receiving a new form of treatment and/or has been on a treatment break (‘holiday’) for liver lesions
Adult subjects with oral lesions undergoing surgical resection (i.e., only patients who are scheduled to undergo a surgery of the head & neck area to remove or biopsy oral lesions will be eligible to participate in the study); patients with previous treatment are eligible
Patients with breast lesions that are non-palpable that require surgical removal
Lesions and/or clip targetable with image guidance
Patient must not have hemorrhagic lesions
Absence of target lesions (> 2.0 cm) on staging CT
Subjects must have solid tumors with malignant lesions in the thorax, abdominal cavity, head and neck region, or extremities (any histology) likely to benefit from palliative radiotherapy; subjects requiring palliative RT for lesions in the spine or lesions adjacent to the spinal cord are excluded from this study
Subjects enrolled into Part 1 must have metastatic lesions where repeated IT injections are not feasible and in whom SC injection is the only viable route of CMP-001 administration, based on Investigator judgment. Subjects with injectable lesions are NOT eligible to participate in Part 1. Subjects enrolled into Part 2 must have metastatic lesions that are amenable to repeated IT injections.
Radioiodine (RAI)-resistant disease as defined by one or more of the following criteria:\r\n* One or more measurable lesions that do not demonstrate RAI uptake\r\n* One or more measurable lesions progressive by RECIST 1.1 =< 14 months of prior RAI therapy\r\n* One or more measurable lesions present after cumulative RAI dose of >= 600 mCi\r\n* One or more measurable lesions that are fludeoxyglucose F-18 (FDG)-avid (> 5 standardized uptake value [SUV]), if positron emission tomography (PET)/CT scan performed; these lesions may also be RAI-avid
Patients with confirmed or suspected liver lesions
Any person with a lesion of the oral mucosa; persons with changes in existing lesions or those who develop new lesions can be re-evaluated, but it is not required
Purely cystic lesions
Participants with paraspinal, paratracheal, and mediastinal pathological lesions larger than 2 centimeters (cm) unless they are previously irradiated
Subjects with active oral lesions or other mouth/throat soreness within 7d of study randomization.