Histologically-confirmed angiosarcoma that is not amenable to curative intent surgery (e.g., metastatic or bulky disease and disease for which surgical resection would carry an unacceptable risk to the patient). Pathology report will be reviewed by sponsor prior to randomization. For this patient, the standard treatment recommendation in the absence of a clinical trial would be combined modality, neoadjuvant chemoradiation followed by curative intent surgical resection Disease that is currently not amenable to surgery, radiation, or combined modality therapy with curative intent Patient must have no prior history of RCC that was resected with curative intent within the past years Surgical resection with curative intent within weeks prior to registration Eligible for surgery with curative intent Have received only one prior radiation treatment course; prior radiation course must have been with curative intent Histologically or cytologically proven diagnosis of advanced stage angiosarcoma that is not amenable to treatment with curative intent; specify site of origin as cutaneous vs. non-cutaneous Evaluation by an attending thoracic surgeon to confirm eligibility for an R resection with curative intent Received at least cycles of one prior regimen administered with curative intent and one of the following: Patient has histologically/cytologically confirmed, non-keratinizing/undifferentiated, EBV-related nasopharyngeal carcinoma, not amenable to curative intent therapy; EBV testing may be completed per institutional standards Subjects have no known curative treatment. Are eligible for a curative treatment option. Must have esophageal cancer that cannot be operated on, or treated with definitive chemoradiation with curative intent, that is advanced, reoccurring or has spread out Disease that is currently not amenable to surgical resection with curative intent as determined by the treating investigator Recurrent/metastatic disease, fulfilling at least one of the criteria defined below:\r\n* Incurable disease as assessed by surgical or radiation oncology\r\n* Metastatic (M) disease\r\n* Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity; patients who decline radical surgery are eligible Has not achieved disease-free status after completion of CCRT administered with curative intent. Documented disease progression occurring within months from the last treatment with curative intent Has newly diagnosed disease (no prior chemotherapy, radiation or surgery with curative intent for this sarcoma diagnosis prior surgery for diagnostic purposes are allowable) Have evidence of persistent, recurrent, or progressive disease for which there is no known or established treatment available with curative intent, after failing at least one course of community standard systemic treatment with chemotherapy (and endocrine therapy if appropriate) Participants must have disease that has progressed on prior treatment and is not amenable to surgical resection or other approved therapeutic options with curative intent. Participants must not be eligible for further therapy that is likely to provide a survival benefit Deemed ineligible for curative intent therapy with surgical resection or liver transplantation Availability of curative treatment option for the patients cancer, whether surgery, chemotherapy, radiation, or combination thereof, unless the patient has documented refusal of curative treatment Availability of and patient acceptance of curative therapy Histologically documented differentiated thyroid cancer with or without metastases, not amenable to curative treatment; or the patient has documented refusal of curative treatment Have evidence of persistent, recurrent, or progressive disease for which there is no known or established treatment available with curative intent, after failing at least one course of community standard systemic treatment with chemotherapy (and endocrine therapy if appropriate) Patients must not be eligible for therapy with curative intent (i.e. surgery, radiation, etc) Availability of and patient acceptance of curative therapy For patients undergoing curative intent resection the following criteria are required: If a curative treatment option in the form of chemoradiation exists in a patient with unresectable disease, this has to be attempted first and must have failed, unless the patient has documented refusal of curative treatment Availability of curative treatment option for the patients cancer, whether surgery, chemotherapy, radiation, or combination thereof, unless the patient has documented refusal of curative treatment ALL patients who have relapsed or have residual disease following treatment with curative intent; ALL patients must have ROR expressed on > % of the leukemia blasts to be eligible Be eligible for curative-intent concurrent chemoradiation therapy Patients will not have any other curative therapeutic option, such as radiation or surgery In the absence of a being treated on a clinical trial, the patient would be recommended to receive neoadjuvant chemoradiation followed by curative intent surgery Patients will not have any other curative therapeutic option, such as radiation or surgery Surgery intent within weeks Fit to receive chemotherapy and radiotherapy with curative intent. Subjects must not be candidates for hepatic surgery or locoregional therapy of liver tumors with curative intent. Has current NSCLC disease that can be treated with curative intent with surgical resection, localized radiotherapy, or chemoradiation Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ? months. Pathologically confirmed diagnosis of stage IIIB/IV recurrent squamous cell NSCLC defined as not amenable to local curative therapy (surgery, radiation, or chemoradiation), and refractory to systemic therapy OR Pathologically or radiologically (fulfilling non-invasive criteria) confirmed diagnosis of HCC not amenable to resection (partial hepatectomy or liver transplantation) or local therapy with curative intent (e.g. radiofrequency ablation) and must not be a liver transplant candidate as defined according to Milan criteria Be appropriate candidates for resection and curative intent therapy in general Patients must not be candidates for curative locoregional treatments; patients with recurrent locoregional disease following surgery and/or radiation for who a resection is unacceptably morbid and unlikely to be curative are eligible; patients must be reviewed at the Moffitt Cutaneous Tumor Board prior to enrolling on trial to verify unresectability Patients who have had prior chemotherapy, radiotherapy, or surgery with curative intent for HNSCC At least months since prior treatment with curative intent and recurrence Histologically confirmed hepatocellular carcinoma not amenable for management with curative intent by surgery or local therapeutic measure; Prior systemic chemotherapy unless it was part of definitive-intent (curative intent) treatment more than months before study entry Eligible for curative treatment (ablation or transplantation) Disease surgically resectable with curative intent Prior curative-intent surgery at least months prior to the nodal recurrence. Surgically eligible for tumor resection with curative intent Recurrent/metastatic disease, fulfilling at least one of the criteria defined below:\r\n* Incurable disease as assessed by surgical or radiation oncology\r\n* Metastatic (M) disease\r\n* Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity; patients who decline radical surgery are eligible Subject must have NSCLC that is not amenable to surgical resection or radiation with curative intent at time of screening. Subjects with recurrent squamous NSCLC after surgical treatment that is not amenable to surgical resection or radiation with curative intent are eligible. Patients who are eligible for curative treatment (ablation or resection or transplantation) Recurrent or persistent measurable disease that has progressed (defined as radiological and/or clinical progression; an increase in cancer antigen [CA]- alone is not sufficient) on or after last therapy (i.e., chemotherapy, hormonal therapy, surgery) and is not amenable to potentially curative intent surgery, as determined by the patient's treating physician. Presence of metastasized or locally advanced, inoperable (curative intent) at enrollment time, histologically proven, midgut carcinoid tumour (to be centrally confirmed). Recurrent NSCLC, who relapse less than one year after completing curative intent therapy Completed all acceptable therapies with curative intent that are the current standard of care for their respective diseases. If no conventional therapy available, patient may participate after review by sponsor. Patients who are candidates for curative surgery or radiotherapy The patient has progressed within months after completion of curative intent (definitive) treatment for localized/locoregionally advanced disease. For subjects receiving adjuvant therapy only, subjects with node positive disease must have undergone treatment of axillary LN with curative intent, or subjects must be scheduled for further treatment of regional lymph nodes with curative intent. Definitive treatment must be planned to be completed within approximately months of randomization Patients must be eligible for curative intent surgical resection Patient must continue to be eligible for curative intent surgical resection Prior radiotherapy with curative intent Prior chemo-radiotherapy with curative intent Patients must not be candidates for curative resection Inability to start study treatment within weeks following the completion of curative intent therapy for rectal adenocarcinoma Disease that is currently not amenable to surgery, radiation, or combined modality therapy with curative intent Completed curative intent therapy, without additional standard of care curative intent therapy feasible within weeks prior to study enrollment After prior curative intent treatment for HNC have estimated risk of recurrence >= -% and fall into one of the below categories (A, OR B, OR C, OR D, OR E, OR F); while exact estimation of the risk of recurrence can be difficult the following categories will be included reflecting patients at substantial risk for tumor recurrence or already with early evidence of recurrence:\r\n* A: Any of the below HNC patients are eligible for treatment on this protocol AFTER completion of curative intent therapy:\r\n** HPV(-) HNC: NC, N, bulky NB disease (>= cm LN/tumor conglomerate)\r\n** HPV(+) HNC: NC, N, AND >= pack years of tobacco use\r\n** HPV(+) HNC with multilevel nodal involvement, AND bulky NB disease (>= cm LN/tumor conglomerate), AND >= pack years of tobacco use\r\n** EBV(+) nasopharyngeal carcinoma (NPC) may be eligible if other criteria under A, or alternative criteria B, or C, or D, or E are met\r\n** HNC with supraclavicular or mediastinal nodal involvement (either HPV+/- or EBV+/-) at the time of curative intent treatment and were treated as part of curative intent therapy (e.g. inclusion in the radiation field)\r\n** Residual mass in area of prior tumor that on biopsy does not show residual tumor, is equivocal/not highly-suspicious on imaging (e.g. positron emission tomography/ computed tomography/magnetic resonance imaging [PET/CT/MRI]), but remains of concern, requires close follow-up AND is not resected/amenable to resection OR immediate palliative treatment\r\n** Non-responders to induction chemotherapy (progressive disease [PD] on induction, or lack of tumor shrinkage (< % per Response Evaluation Criteria in Solid Tumors [RECIST])\r\n** Interrupted treatment course or lower than intended radiation dose i.e. interruption of radiation by >= weeks (cumulative), or delivery of =< Gy as part of a radiation based treatment (that was NOT a de-escalation approach)\r\n* B: Patient treated with salvage treatment (i.e. salvage surgery or re-irradiation) for residual or recurrent tumor after prior radiation based therapy (either HPV+ or HPV- or EBV+) AND not a candidate for additional curative intent therapy (for various reasons including poor performance status, comorbidities, refusal of patient, prior radiation or re-irradiation, etc); positive margins or residual tumor may still be acceptable); patients should also not be appropriate for systemic palliative therapy (e.g. in the case of overt disease)\r\n* C: Mx or indeterminate distant lesions that are not appropriate for either local radiation/stereotactic body radiation therapy (SBRT) treatment and also not appropriate for initiation of palliative system therapy (e.g. in the setting of overt metastatic disease); such lesions should be negative/equivocal by PET imaging and if amenable negative by biopsy, but remain of concern and require close follow-up\r\n* D: Oligometastatic disease treated with SBRT or other curative-intent therapy (e.g. surgery or radiofrequency ablation (RFA), etc) for oligometastatic disease\r\n* E: Microscopic or very low volume residual tumor after surgery or radiation based treatment (including salvage treatment or SBRT for oligometastatic disease), AND not a candidate for either additional curative intent therapy (for various reasons including feasibility, poor performance status, comorbidities, refusal of patient, prior radiation or re-irradiation, etc) AND also not a candidate for systemic palliative therapy (for various reasons including microscopic/non-[RECIST] measurable low volume disease); very low volume disease is defined as non-RECIST measurable)\r\n* F: Patients with multiple recurrences or multiple primaries: specifically patients who had malignant or pre-malignant tumors/changes (with severe dysplasia present), who have undergone surgery >= times, and currently do not have an indication for additional (adjuvant) treatment such as radiation, or surgery, or other treatment; this may include multiple recurrences/incidences of early stage tumors or premalignant lesions, however at least one lesion needs to show squamous cell carcinoma on pathology\r\n* There may be additional scenarios for patients that are considered very high risk for disease recurrence and not appropriate for either curative or standard of care palliative therapy; such patients can be considered for enrollment after discussion and approval by the principal investigator (PI) and/or co-PI Not amenable to treatment with curative intent Patients scheduled to undergo surgical resection for curative intent during study participation Patient undergoing any resection requiring an anastomosis to the esophagus for curative intent; including but not limited to esophagectomy or total gastrectomy Completed cancer treatment with curative intent Patient has histologically proven colorectal cancer or polyp(s) that is planned to be treated by surgical resection performed with curative intent Patients who are receiving a course of radiation therapy for curative or adjuvant intent Patients who have been diagnosed with locally advanced unresectable NSCLC undergoing definite chemo-radiation with curative intent Macroscopic resection of the tumor via TORS must be planned with curative intent Eligible for at least cycles of standard of care AML chemotherapy that will result in moderate to severe myelosuppression and have curative intent Patients may be enrolled between months and years AFTER completion of curative-intent therapy (including surgery, radiotherapy, and/or chemotherapy) Planned curative intent chemotherapy, delivered either concurrently or sequentially in combination with radiotherapy Planned standard of care surgery with curative intent for pancreatic adenocarcinoma Histologically confirmed cancer that is advanced; metastatic; or otherwise not suitable for surgical resection with curative intent Must be in acceptable health to undergo radiation therapy and curative intent surgery as assessed by UNC surgeons and radiation oncologist Must receive their neoadjuvant radiation therapy and curative intent surgery at UNC Hospitals Chapel Hill location Medical conditions precluding radiation therapy or curative intent surgery Planned standard of care surgery with curative intent for squamous cell carcinoma Planned standard of care surgery with curative intent for pancreatic adenocarcinoma Planned standard of care surgery with curative intent for squamous cell carcinoma Patients who underwent, currently undergoing or planned to start radiation treatment with curative, adjuvant or palliative intent, who have not yet had their first post-treatment visit Patients must have completed all therapy for curative intent at least six months prior to chart audit Disease that is not amenable to surgery, radiation, or combined modality therapy with curative intent. Prior treatment with > line of chemotherapy for metastatic breast cancer or for locoregional recurrence that was not amenable to resection or radiation therapy with curative intent. Experienced PD on > endocrine therapies for metastatic breast cancer or for locoregional recurrence that was not amenable to resection or radiation therapy with curative intent. For phase Ib only: Pretreated patients, and not amenable to further therapy with curative intent. This part is open to pretreated patients regardless of the number of previous treatment lines. For phase II only: Patients who received a maximum of two prior systemic regimens for recurrent and/or metastatic disease and not amenable to further therapy with curative intent. No prior curative attempts for this cancer, (i.e., surgery, radiation and/or other)