This phase II trial studies how well chemotherapy and/or metastasectomy work in treating patients with colorectal adenocarcinoma that has spread to the lungs (metastases). Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Metastasectomy is a surgical procedure that removes tumors formed from cells that have spread from other places in the body. It is not yet known if chemotherapy and metastasectomy together works better in treating patients with metastatic colorectal adenocarcinoma with lung metastases.
PRIMARY OBJECTIVES: I. To compare recurrence-free survival in patients with "low risk" lung-limited metastatic colorectal cancer (mCRC) undergoing pulmonary metastasectomy with or without perioperative chemotherapy. II. To compare overall survival in patients with "high risk" lung-limited mCRC receiving systemic chemotherapy with or without surgical resection. SECONDARY OBJECTIVES: I. To compare grade 3 and 4 adverse events in patients receiving surgical resection and/or chemotherapy in the management of lung-limited mCRC. EXPLORATORY OBJECTIVES: I. To evaluate for changes in circulating tumor deoxyribonucleic acid (DNA) following surgical resection and/or systemic chemotherapy in patients with lung-limited mCRC. OUTLINE: Patients are assigned to 1 of 2 risk groups (low or high). GROUP 1 (LOW RISK): Patients are randomized to 1 of 2 groups. GROUP 1A: Patients receive standard of care chemotherapy for 3 months prior to and 3 months after undergoing metastasectomy in the absence of disease progression or unacceptable toxicity. GROUP 1B: Patients undergo metastasectomy. GROUP 2 (HIGH RISK): All high risk patients receive standard of care chemotherapy for 3 months in the absence of disease progression or unacceptable toxicity. Patients without progressive disease after 3 months are then randomized to 1 of 2 groups. GROUP 2A: Patients undergo metastasectomy. GROUP 2B: Patients continue standard of care chemotherapy for 6 months in the absence of disease progression or unacceptable toxicity. Patients with stable disease or radiographic response after 6 months may then cross over to Group 2A. After completion of study treatment, patients are followed up periodically for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Receive chemotherapy
Undergo pulmonary metastasectomy
Washington University School of Medicine
St Louis, Missouri, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Baylor Colllege of Medicine
Houston, Texas, United States
M D Anderson Cancer Center
Houston, Texas, United States
University Health Network Princess Margaret Cancer Center P2C
Toronto, Ontario, Canada
University of Montreal
Montreal, Quebec, Canada
Recurrence-free survival (Low risk)
The primary objective for the low risk group is to evaluate the efficacy of chemotherapy plus surgical resection versus surgical resection alone measured by recurrence-free survival (RFS). The event includes recurrence and death due to any cause. Patients will be stratified at randomization according to three variables: age (age \>= 60 years vs age \< 60 years), RAS mutation status (mutant vs wild type), and location of primary tumor within colon/rectum (right/cecum/ascending colon/hepatic flexure/transverse colon vs left/distal to transverse colon).
Time frame: Up to 2 years
Overall survival (High risk)
The primary objective for the high-risk group is to evaluate the efficacy of chemotherapy plus surgical resection versus chemotherapy alone measured by overall survival (OS). The event includes death due to any cause. Patients will be stratified at randomization according to 4 variables: response to chemotherapy in the preceding three months of treatment (complete or partial response vs stable disease by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria), RAS mutated vs RAS wild type tumors, right versus left-sided primary tumors, and oxaliplatin-based vs irinotecan-based chemotherapy in the initial treatment period on study.
Time frame: Up to 2 years
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