Metastatic Colorectal Cancer: Evaluating Radiation, Ablation, and Surgery

What is the Purpose of this Study?

This study focuses on individuals who have advanced colorectal cancer that has spread up to 4 body sites. The purpose of the study is to compare the usual treatment alone to ablative local therapy (ALT) to all known metastatic tumor sites plus the usual treatment. The usual treatment is treatment with intravenous and/or oral medications (systemic therapy). These medications help stop the cancer sites from getting larger and prevent the spread of the cancer to additional body sites. ALT is commonly used to treat all known tumor sites and may be performed by surgery, radiation therapy, heat with microwave ablation, or other methods. This study will use radiation therapy and potentially surgery and/or heat. To measure the effectiveness of the addition of ALT to treatment, researchers will examine whether this approach increases the life of patients by 17 months or more compared to the usual approach. Participants will be assigned to one of two groups. Group 1 will receive the usual drug therapy used to treat metastatic colorectal cancer plus ALT to all known metastatic sites. Group 2 will receive the usual systemic drug therapy used to treat metastatic colorectal cancer and may also receive palliative local therapies to metastatic sites such as surgery or radiation to help relieve uncontrolled symptoms, such as pain, caused by cancer.

Eligibility

* PRE-REGISTRATION (STEP 0): Histologically-confirmed metastatic colorectal adenocarcinoma
* PRE-REGISTRATION (STEP 0): No known microsatellite instable (MSI) tumor
* PRE-REGISTRATION (STEP 0): No known BRAF V600E mutation
* PRE-REGISTRATION (STEP 0): Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. No known peritoneal and/or omental metastases. If radiologic studies suggest the presence of peritoneal disease, a diagnostic laparoscopy is recommended to verify the absence of peritoneal implants

Inclusion Criteria:

* PRE-REGISTRATION (STEP 0): Histologically-confirmed metastatic colorectal adenocarcinoma
* PRE-REGISTRATION (STEP 0): No known microsatellite instable (MSI) tumor
* PRE-REGISTRATION (STEP 0): No known BRAF V600E mutation
* PRE-REGISTRATION (STEP 0): Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. No known peritoneal and/or omental metastases. If radiologic studies suggest the presence of peritoneal disease, a diagnostic laparoscopy is recommended to verify the absence of peritoneal implants
* PRE-REGISTRATION (STEP 0): Primary tumor is already resected OR primary tumor is surgically amenable to resection, as determined by consultation and documentation with surgeon or documentation of discussion in the institutional multi-disciplinary tumor board where a surgeon confirms resectability. Patients with unresectable primary tumors are not eligible
* PRE-REGISTRATION (STEP 0): Four (4) or fewer apparent sites of metastatic disease based on review by local medical team of baseline radiographic imaging obtained prior to initiation of systemic therapy.
* Sites of metastatic disease must be radiographically evident, but pathologic confirmation is not required.
* Liver-only metastatic disease is NOT permitted. For patients with liver metastases, there must be at least one other site of metastasis in addition to the liver to be eligible for this study.
* Metastatic lesions must be amenable to any combination of surgical resection, microwave ablation, and/or stereotactic ablative body radiation therapy (SABR). SABR is required for at least one lesion. Therefore, the patient must be seen by a radiation oncologist in consultation to verify eligibility.
* Single sites include:
* Each hemiliver (right and left), each lobe of the lungs, each adrenal gland, lymph nodes amenable to a single resection or treatment in a single SABR field, bone metastases amenable to treatment in a single SABR field
* PRE-REGISTRATION (STEP 0): Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
* PRE-REGISTRATION (STEP 0): A maximum of 16 weeks (4 months) of systemic therapy may be administered prior to pre-registration
* REGISTRATION (STEP 1): Patients must have no overt evidence of disease progression during systemic therapy prior to registration
* REGISTRATION (STEP 1): Not eligible for hepatic artery infusion pump (HAIP) therapy or benefit of HAIP therapy is undefined
* REGISTRATION (STEP 1): Patients must have measurable disease per RECIST v1.1
* REGISTRATION (STEP 1): Patients must be receiving (or have received) first-line systemic therapy for metastatic disease for a minimum of 16 weeks (4 months) and a maximum of 24 weeks (6 months)
* REGISTRATION (STEP 1): Prior definitive therapy, including adjuvant chemotherapy, must have been completed at least 12 months prior to diagnosis of metastatic disease
* REGISTRATION (STEP 1): Not pregnant and not nursing, because this study involves an agent or treatment that has known genotoxic, mutagenic, and teratogenic effects.
\* Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 14 days prior to registration is required
* REGISTRATION (STEP 1): Age \>= 18 years
* REGISTRATION (STEP 1): Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
* REGISTRATION (STEP 1): Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* REGISTRATION (STEP 1): Platelet count \>= 50,000/mm\^3
* REGISTRATION (STEP 1): Creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \>= 30 mL/min
\* Calculated using the Cockcroft-Gault equation
* REGISTRATION (STEP 1): Total bilirubin =\< 1.5 x ULN
* REGISTRATION (STEP 1): Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\]) / alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x ULN
\* In the event of metastatic liver disease, =\< 5 x ULN
* REGISTRATION (STEP 1): Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Note: HIV testing is not required for eligibility
* REGISTRATION (STEP 1): No other planned concurrent investigational agents while on study

Exclusion Criteria:

* N/A

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Where can I participate?

Cedars-Sinai Cancer at Beverly Hills (THO) : Abrahm Levi
Cedars-Sinai Cancer at SOCC : Abrahm Levi

More about this Clinical Trial

What is the full name of this clinical trial?

A022101: A Pragmatic Randomized Phase III Trial Evaluating Total Ablative Therapy for Patients with Limited Metastatic Colorectal Cancer: Evaluating Radiation, Ablation, and Surgery

Study Details

Disease Type/Condition

Colon, Rectum

Principal Investigator

Gong, Jun

Co-Investigators

Andrew Hendifar, Arsen Osipov, David Hoffman, Jeremy Lorber, Kevin Scher

Age Group

Adult

Phase

III

IRB Number

STUDY00003115

ClinicalTrials.gov ID

NCT05673148

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Abrahm Levi

Abrahm.Levi@cshs.org