Systemic Therapy With or Without Local Consolidative Therapy in Treating Participants With Oligometastatic Solid Tumor

PRIMARY OBJECTIVES:

I. In patients with oligometastatic malignancies, to assess progression free survival (PFS)
with upfront local consolidative therapy (LCT) versus (vs.) no LCT among randomized patients.

SECONDARY OBJECTIVES:

I. In patients with oligometastatic malignancies, to assess overall survival (OS) with
upfront LCT vs. no LCT among randomized patients.

II. In patients with oligometastatic malignancies, to assess time to next line systemic
therapy with upfront LCT vs. no LCT.

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.

VI. In patients with oligometastatic malignancies, to assess quality of life 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 the systemic immune activating effects of radiation.

OUTLINE: Participants are randomized to 1 of 2 arms.

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

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

After completion of study, participants are followed up every 18 weeks for 1 year

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

- Within 4 weeks prior to study enrollment: Absolute neutrophil count (ANC) >= 500/mcL

- Within 4 weeks prior to study enrollment: Platelets >= 25,000/mcL

- Within 4 weeks prior to study enrollment: Hemoglobin >=7 g/dL

- Within 4 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

- Within 4 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

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 4 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