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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03599752
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : May 24, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
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 Drug: Chemotherapy Procedure: Metastasectomy Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 365 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Role of Multimodality Management in Risk-Stratified Patients With Lung-Limited Metastatic Colorectal Cancer
Actual Study Start Date : July 2, 2018
Estimated Primary Completion Date : January 31, 2023
Estimated Study Completion Date : January 31, 2023

Arm Intervention/treatment
Experimental: 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.
Drug: Chemotherapy
Receive chemotherapy
Other Names:
  • Chemo
  • Chemotherapy (NOS)
  • Chemotherapy, Cancer, General

Procedure: Metastasectomy
Undergo pulmonary metastasectomy

Experimental: Group 1B (metastasectomy)
Low risk patients undergo metastasectomy.
Procedure: Metastasectomy
Undergo pulmonary metastasectomy

Experimental: Group 2A (metastasectomy)
High risk patients undergo metastasectomy.
Procedure: Metastasectomy
Undergo pulmonary metastasectomy

Experimental: 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.
Drug: Chemotherapy
Receive chemotherapy
Other Names:
  • Chemo
  • Chemotherapy (NOS)
  • Chemotherapy, Cancer, General




Primary Outcome Measures :
  1. Recurrence-free survival (Low risk) [ Time Frame: Up to 2 years ]
    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).

  2. Overall survival (High risk) [ Time Frame: Up to 2 years ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03599752


Contacts
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Contact: Mara Antonoff, MD 713-745-4530 mbantonoff@mdanderson.org

Locations
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United States, Massachusetts
Brigham and Women's Hospital Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Mara B. Antonoff    713-745-4530    mbantonoff@mdanderson.org   
Principal Investigator: Raphael Bueno         
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Mara B. Antonoff    713-745-4530    mbantonoff@mdanderson.org   
Principal Investigator: Dennis A. Wigle         
United States, Missouri
Washington University School of Medicine Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Mara B. Antonoff    713-745-4530    mbantonoff@mdanderson.org   
Principal Investigator: Benjamin D. Kozower         
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Contact: Mara B. Antonoff    713-745-4530    mbantonoff@mdanderson.org   
Principal Investigator: David R. Jones         
United States, North Carolina
Duke University Medical Center Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Mara B. Antonoff    713-745-4530    mbantonoff@mdanderson.org   
Principal Investigator: David H. Harpole         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Mara B. Antonoff    713-745-4530      
Principal Investigator: Mara B. Antonoff         
Canada, Ontario
University Health Network Princess Margaret Cancer Center P2C Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Mara B. Antonoff    713-745-4530    mbantonoff@mdanderson.org   
Principal Investigator: Thomas K. Waddell         
Canada, Quebec
University of Montreal Not yet recruiting
Montreal, Quebec, Canada, H3T 1J7
Contact: Mara B. Antonoff    713-745-4530    mbantonoff@mdanderson.org   
Principal Investigator: Moishe Liberman         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Mara B Antonoff M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03599752    
Other Study ID Numbers: 2017-0905
NCI-2018-01456 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-0905 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: July 26, 2018    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Adenocarcinoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type