This phase II trial studies how well systemic therapy with or without local consolidative therapy work in treating patients with solid tumor that has spread to 1 site of other places in the body. Treatment with up-front local consolidative therapy may be better in helping to control the disease.

PRIMARY OBJECTIVES:

I. In patients with oligometastatic malignancies, to assess PFS with upfront LCT vs. no LCT among randomized patients. In this analysis each disease site will be analyzed separately.

SECONDARY OBJECTIVES:

I. In patients with oligometastatic malignancies, to assess OS with upfront LCT vs. no LCT among randomized patients. In this analysis disease sites will be amalgamated and analysis will compare randomized arms.

II. In patients with oligometastatic malignancies, to assess time to next line systemic therapy with upfront LCT vs. no LCT. The subsequent line of systemic therapy will be defined as the subsequent line after protocol specified systemic therapy.

III. In patients with oligometastatic malignancies, to assess time to new lesion failure with upfront LCT vs. no LCT.

IV. To assess safety/tolerability of upfront LCT in patients with oligometastatic malignancies.

V. In patients with oligometastatic malignancies, to assess quality of life with upfront LCT vs. no LCT. Separate analyses will assess 1) all disease sites amalgamated and 2) all disease sites analyzed separately.

VI. In patients with oligometastatic malignancies, assess time to local failure with upfront LCT vs no LCT.

VII. In patients with oligometastatic prostate cancer, assess radiographic progression-free survival with upfront LCT vs no LCT. VIII. In patients with oligometastatic castrate-sensitive prostate cancer, assess castrateresistance free survival with upfront LCT vs no LCT.

EXPLORATORY OBJECTIVES:

I. To identify predictive/prognostic biomarkers that are associated with a benefit to LCT across disease sites.

II. To investigate alterations in biomarker profile over time and in response to radiation delivery.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive up-front standard of care LCT including but not limited to surgical resection, cryotherapy, and radiofrequency ablation. Patients then receive routine drug therapy.

ARM II: Patients receive routine drug therapy. Patients may later receive LCT at the discretion of doctor.

After completion of study, patients are followed up every 18 weeks.

Inclusion Criteria:

• Oligometastatic solid tumors (see protocol for relevant disease sites) patients (=< 5 metastatic lesions at the time of study entry)
• Candidate for definitive local therapy to all sites of active disease per the discretion of the treating physicians
• No more than 4 prior lines of systemic therapy administered to treat metastatic disease
• Pathologically confirmed diagnosis of cancer as specified in protocol
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) >= 500/mcL (performed within 6 weeks prior to study enrollment)
• Platelets >= 25,000/mcL (performed within 6 weeks prior to study enrollment)
• Hemoglobin >=7 g/dL (performed within 6 weeks prior to study enrollment)
• Serum total bilirubin =< 1.5 mg/dl (except for subjects with Gilbert syndrome, who may have total bilirubin < 3.0 mg/dl) OR direct bilirubin =< upper limit normal (ULN) for subjects with total bilirubin levels > 1.5 mg/dl (performed within 6 weeks prior to study enrollment)
• Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) =< 3 X ULN OR =< 5 X ULN for subjects with liver metastases (performed within 6 weeks prior to study enrollment)

Exclusion Criteria:

• Has a diagnosis of active scleroderma, lupus, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy

• Metastatic effusion (e.g. pleural effusion or ascites). Note that patients with an effusion that is too small to sample will be eligible for the trial

• Diffuse metastatic processes including leptomeningeal disease, diffuse bone marrow involvement, and peritoneal carcinomatous, which by the discretion of the treating physician cannot be treated definitively

• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

• In the event that a curative systemic option exists for metastatic disease from a given disease site. First-line metastatic patients (those patients who have had no prior lines of systemic therapy targeting their metastatic disease) are only eligible for enrollment if they have completed their curative systemic therapy per the judgment of the treating oncologist and have persistent disease

• Is pregnant or expecting to conceive within the projected duration of the trial at the screening visit

  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 6 weeks prior to study registration up to the first fraction of radiation
  • Note: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• Additional diagnosis of another primary malignancy outside of the malignancy being treated on trial that per the discretion of the treating physicians and investigational team offers a substantial risk to the patient's life (e.g. primary lung cancer definitively treated in the past 6 months would offer a significant risk to the patient's life, while a basal cell carcinoma treated with local excision would not)