No previous chemotherapy or radiation therapy
Patients who have participated in a marathon, triathlon, or other endurance-related physical activity within the previous 24 months
Patients who have received previous vaginal, pelvic, or abdominal irradiation
Patient must be considered able to tolerate systemic chemotherapy combined with pelvic radiation therapy, and a radical cystectomy (if necessary) by the joint agreement of the participating urologist, radiation oncologist, and medical oncologist
Consultation, agreement, and documentation in the patients chart by a radiation oncologist that patient is suitable to receive radiotherapy per this protocol
Patients who have received previous treatment for antecedent hematological disorders (AHD) with 5-azacitidine, decitabine, or low dose cytarabine will be excluded
Patients with cervix cancer who have received any previous radiation or chemotherapy
Previous pelvic irradiation, prostate brachytherapy, or bilateral orchiectomy
Patients must not be expecting to receive radiation or additional chemotherapy
STEP I: Patients may have a history of current or previous deep vein thrombosis or pulmonary embolism but must be willing to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation
Patients must not have a severe psychiatric illness, including major depression or any previous suicide attempts
Previous steroid treatment and/or radiation treatment is not allowed unless it is for the emergent management of a mediastinal mass; emergent steroid treatment and/or radiation treatment should stop once protocol therapy is initiated
Previous pelvic radiation for bladder or prostate cancer if performed < 12 months prior to enrollment into the study
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
If patients have had a potential index lesion radiated, it must have progressed post radiation therapy to be used as a measurable eligibility lesion
Current systemic chemotherapy or radiation therapy that potentially causes bone marrow suppression that would preclude safe treatment of HSIL
Previous randomization in the present study
HCC patients only: prior regional treatments for liver metastasis are permitted including:* Selective internal radiation therapy such as brachytherapy, cyber knife, radiolabeled microsphere embolization, etc.* Hepatic artery chemoembolization* Hepatic artery embolization* Hepatic artery infusional chemotherapy* Radiofrequency ablation* NOTE: patients must be >= 4 weeks from treatment and show progressive measurable/evaluable disease in the liver after regional therapy or must have measurable disease outside the liver
Patients with >= grade 2 hypothyroidism due to history of autoimmunity are not eligible; note: hypothyroidism due to previous irradiation on thyroidectomy will not impact eligibility
No previous chemotherapy within 16 days prior to enrollment except for bleomycin which cannot have been given within 5 days prior to enrollment
Radiotherapy may be given before or after protocol treatment per standard of care guidelines; when radiotherapy is planned prior to protocol treatment administration, patients may be registered and screened while receiving radiation* Post-mastectomy radiotherapy is required for all patients with the following:** Primary tumor >= 5 cm (prior to neoadjuvant chemotherapy [clinically] or at the time of definitive surgery) or involvement of lymph nodes at the time of definitive surgery** For patients with primary tumors < 5 cm or without lymph node involvement prior to neoadjuvant chemotherapy and at the time of definitive surgery, provision of post-mastectomy radiotherapy is at the discretion of the treating physician** Radiation of regional nodal basins is at the discretion of the treating radiation oncologist* NOTE: Breast radiotherapy (whole breast or partial) is required for patients who underwent breast-conserving therapy, including lumpectomy or partial mastectomy
Current systemic chemotherapy or radiation therapy that potentially causes bone marrow suppression that would preclude safe treatment of HSIL; Note: Kaposis sarcoma limited to the skin is not exclusionary unless requiring systemic chemotherapy
Patients with secondary APL are excluded; this includes all patients with APL that may have resulted from prior treatment (chemotherapy or radiation)
Previous local therapy of any KS-indicator lesion unless the lesion has clearly progressed since that local treatment; any prior local treatment to indicator lesions regardless of the elapsed time should not be allowed unless there is evidence of clear-cut progression of said lesion
Previous therapy with anthracyclines or taxanes for any malignancy
Previous treatment with any other compound that targets CD40
Patients may not have had any prior systemic treatment for this malignancy (for example chemotherapy or somatostatin analogues); prior palliative radiation is permitted but radiated lesions may not be used for measurement
Patients who have had a hysterectomy or are planning to have an adjuvant hysterectomy following radiation as part of their cervical cancer treatment are ineligible
At least 4 weeks away from any previous antineoplastic or investigational agent; patients may receive hydroxyurea or glucocorticoids for suppression of leukocytosis, but these must be stopped at least 24 hours (h) prior to initiation of therapy
Patients must have had at least two prior chemotherapeutic or biologic (e.g. rituximab alone) regimens and not currently eligible for standard curative options; steroids alone and local radiation do not count as regimens
No prior therapy with enzalutamide (previous chemotherapy and/or other AR-targeted approaches is allowed)
Patients must not have any unresolved wounds from previous surgery
Prior radiation allowed (no restriction on amount); measurable lesion(s) may not have been previously irradiated
Patients with acute or lymphoma forms must have received at least one cycle of combination chemotherapy (with or without mogamulizumab) or interferon (with or without zidovudine and/or arsenic); individuals with chronic or smoldering acute T-cell lymphoma (ATL) are not required to have had prior treatment or could have received any number of previous courses of therapy
Patients must have no previous radiotherapy or chemotherapy other than corticosteroids
If primary disease in the thoracic cavity was previously treated with local therapy in the form of surgery, any local/regional disease recurrence should be technically treatable with SBRT or hypofractionated radiation after induction systemic therapy.
If a patient has progressed in previous areas of primary disease that received definitive doses of radiation, these patients would require re-irradiation in previous high dose anatomic areas and are not eligible for this study.
Patients on supraphysiologic doses of steroids or use of such within the previous six weeks
Patients with evidence of another malignancy or benign tumor requiring chemotherapy or radiation therapy are excluded; however, those patients with a plexiform neurofibroma requiring treatment will be eligible as selumetinib has documented activity in plexiform neurofibromas
Patients must have at least one lesion that has not previously been irradiated (and is not within a previously radiated field) and for which palliative radiation is potentially indicated and could be safely delivered at the radiation doses specified in this protocol; this lesion must not be the only measurable lesion so that it is still possible to determine the response rate outside of the radiation treatment field; this lesion must not be within the central nervous system (CNS) (brain or spinal cord) or requiring urgent or emergent palliative radiation given the timing of radiation specified on this protocol; furthermore, this lesion: * For cohort 1 (NSCLC cohort)  the lesion to be irradiated must be in the lung, lymph nodes, adrenal gland or liver * For cohort 2 (colorectal cohort)  the lesion to be irradiated must be in the liver
Receipt of prior radiotherapy or condition for any reason that would contribute radiation dose that would exceed tolerance of normal tissues, at the discretion of the treating physician
Previous enrollment in the present study
Disease that is currently not amenable to surgery, radiation, or combined modality therapy with curative intent
Patients must have had one prior systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic carcinoma of the cervix (e.g.; paclitaxel/cisplatin, paclitaxel/cisplatin/bevacizumab), at least one which must have contained bevacizumab* NOTE: Patients are allowed to receive 1-2 prior regimens for management of recurrent, persistent or metastatic carcinoma of the cervix; patients who have received more than two prior systemic regimens for management of recurrent, persistent or metastatic carcinoma of the cervix are NOT eligible* NOTE: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic carcinoma of the cervix; adjuvant therapy includes cisplatin given concurrent with primary radiation therapy (CCRT) and adjuvant chemotherapy given following the completion of concurrent chemotherapy and radiation therapy (e.g., paclitaxel and carboplatin for up to 4 cycles)
Tumors within previous radiated field will be designated non-target lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
Previous treatment with talimogene laherparepvec (T-VEC) or any other oncolytic virus
Previous chemotherapy or chemoradiotherapy outside of the InPACT trial
Patients for whom radiation therapy (RT) to the affected breast or chest wall and regional nodal areas is clinically indicated as per NCCN treatment guidelines, should receive RT after randomization when possible, and receive MK-3475 (pembrolizumab) concurrent with RT, if randomized to the experimental arm; however, RT administered, or initiated, prior to registration is also allowed; pembrolizumab may be added to ongoing radiation, or started after its completion, if randomized to the experimental arm, provided there are no > grade 2 radiation-related skin toxicities; patients who have not yet started radiation must specify at the time of screening registration whether or not they will receive RT and the extent of intended RT
Previous radiotherapy to the scalp, cranium, brain, or skull base and radiation-induced meningiomas
Patients must not have received prior treatment with talimogene laherparepvec (T-VEC) or other oncolytic virus agents
Previous therapy with at least radiotherapy and temozolomide
Previous chemotherapy for any other disease site if given within 3 years prior to step 1
Previous treatment with talimogene laherparepvec or other herpes virus based therapy; (prior therapy with checkpoint inhibitors and/or other immunotherapy is allowed)
Patients who have previously been treated with talimogene laherparepvec, any other oncolytic virus or pelvic radiation are ineligible
Patients must not have received prior whole brain radiation therapy; previous SRS/SRT done at least 3 weeks from the planned start of IPdR therapy is acceptable; SRS/SRT/fractionated boosts or neurosurgery can be performed once the dose limiting toxicity (DLT) assessment has been completed, if felt clinically necessary
Prior chemotherapy, targeted biological therapy (e.g. sorafenib), surgery, transarterial chemoembolization (TACE), ablation for present disease is acceptable
Patients must have histologically confirmed glioblastoma that is progressive or recurrent following radiation therapy and temozolomide according to the Response Assessment in Neuro-Oncology (RANO) criteria with:* New contrast-enhancing lesion outside of radiation field on decreasing, stable, or increasing doses of corticosteroids* Increase by >= 25% in the sum of the products of perpendicular diameters between the postradiotherapy scan with the smallest tumor measurement and a scan at least 12 weeks from completion of radiation therapy (RT) + temozolomide (TMZ), on stable or increasing doses of corticosteroids** Note: clinical deterioration not attributable to concurrent medication or comorbid conditions is sufficient to declare progression on current treatment but not for entry onto a clinical trial for recurrence
The use of memantine during or following radiation is NOT allowed