Chemotherapy and/or Metastasectomy in Treating Patients With Metastatic Colorectal Adenocarcinoma With Lung Metastases

NCT ID: NCT03599752

Last Updated: 2026-01-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-02
• Study Completion Date: 2030-01-31

Brief Summary

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.

Detailed Description

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.

Conditions

Colorectal Adenocarcinoma; Colorectal Carcinoma Metastatic in the Lung; Stage IV Colorectal Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1A (chemotherapy, metastasectomy)

Low risk 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 Type: EXPERIMENTAL

Chemotherapy

Intervention Type: DRUG

Receive chemotherapy

Metastasectomy

Intervention Type: PROCEDURE

Undergo pulmonary metastasectomy

Group 1B (metastasectomy)

Low risk patients undergo metastasectomy.

Group Type: EXPERIMENTAL

Metastasectomy

Intervention Type: PROCEDURE

Undergo pulmonary metastasectomy

Group 2A (metastasectomy)

High risk patients undergo metastasectomy.

Group Type: EXPERIMENTAL

Metastasectomy

Intervention Type: PROCEDURE

Undergo pulmonary metastasectomy

Group 2B (chemotherapy)

High risk 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.

Group Type: EXPERIMENTAL

Chemotherapy

Intervention Type: DRUG

Receive chemotherapy

Interventions

Chemotherapy

Receive chemotherapy

Intervention Type: DRUG

Metastasectomy

Undergo pulmonary metastasectomy

Intervention Type: PROCEDURE

Other Intervention Names

Chemo; Chemotherapy (NOS); Chemotherapy, Cancer, General

Eligibility Criteria

Inclusion Criteria

• Histological confirmation of colorectal adenocarcinoma
• Metastatic colorectal cancer involving the lung classified as determined by the treating clinical team
• Diagnosis of colorectal metastasis to lung made either histologically with trans-thoracic needle biopsy or clinically based on radiographic imaging
• Identification as a medically appropriate candidate for surgical resection of the lung metastasis (metastases) according to the evaluating cardiothoracic surgeon. Standard justification for deeming a patient medically operable based on:

• Pulmonary reserve adequate to tolerate complete resection of all intrathoracic disease, as deemed by thoracic surgeon, which may be determined by:

• Baseline forced expiratory volume in one second (FEV1) > 40% predicted
• Post-operative predicted FEV1 > 30% predicted
• Diffusion capacity of the lung for carbon monoxide (DLCO) > 40% predicted
• Absent baseline hypoxemia and/or hypercapnia
• Exercise oxygen consumption > 50% predicted
• Absent severe pulmonary hypertension
• Absent severe cerebral, cardiac, or peripheral vascular disease
• Absent severe chronic heart disease
• Ability to tolerate surgical resection and acceptable operative risk as deemed by thoracic surgeon based on performance status and medical comorbidities
• Identification as a medically appropriate candidate for systemic chemotherapy at the discretion of the evaluating medical oncologist
• Resection/definitive therapy of primary colorectal tumor with no suspicion of recurrence. Prior radiation to a rectal adenocarcinoma is permitted
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Ability to provide informed consent for participation
• Leukocytes >= 2,000/mcL
• Absolute neutrophil count >= 1,000/mcL
• Hemoglobin >= 9.0 gm/dL
• Platelet count >= 100,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (except patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
• Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl >= 50 mL/min (if using the Cockcroft-Gault formula)
• Patients (men and women) of child bearing potential should use an effective (for them) method of birth control throughout their participation in this study

Exclusion Criteria

• Tumor involvement at other metastatic sites (e.g., liver, distant lymph nodes) that has not been definitively treated. Prior surgical resection for metastatic disease at other (non-pulmonary) sites is permitted
• Presence of intact primary colorectal adenocarcinoma (or of an anastomotic recurrence)
• Previous radiotherapy to a lung metastasis that is still detectable radiographically
• Known dihydropyrimidine dehydrogenase (DPD) deficiency that would preclude the patient from tolerating 5- fluorouracil chemotherapy
• Prior intolerance of systemic therapies used as standard regimens in the treatment of metastatic CRC that would prohibit further receipt of systemic chemotherapy and/or biologic agents -e.g.,5-fluorouracil, oxaliplatin, irinotecan, anti-VEGF therapies (e.g., bevacizumab, ramucirumab), or anti-EGFR therapies (e.g., cetuximab, panitumumab, for patients with RAS wild-type colorectal tumors)
• Prior therapy with regorafenib or trifluridine/tipiracil (TAS-102) for metastatic/unresectable colorectal cancer
• Synchronous primary or prior malignancy in the past 5 years other than non-melanomatous skin cancer or in situ cancer
• Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mara B. Antonoff, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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

Countries

United States; Canada

Related Links

http://www.mdanderson.org

MD Anderson Cancer Center

Other Identifiers

NCI-2018-01456

Identifier Type: REGISTRY

Identifier Source: secondary_id

2017-0905

Identifier Type: OTHER

Identifier Source: secondary_id

2017-0905

Identifier Type: -

Identifier Source: org_study_id