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Liver Surgery and Chemotherapy in Treating Patients With Colorectal Cancer With Liver Metastases That Can Be Removed by Surgery and Lung Metastases That Cannot Be Removed by Surgery

Primary Purpose

Metastatic Colorectal Carcinoma, Metastatic Malignant Neoplasm in the Liver, Metastatic Malignant Neoplasm in the Lung

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Chemotherapy

Laboratory Biomarker Analysis

Metastasectomy

Quality-of-Life Assessment

Therapeutic Conventional Surgery

About this trial

This is an interventional treatment trial for Metastatic Colorectal Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with synchronous or metachronous diagnosis of resectable liver metastases by computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen
- Patients requiring percutaneous or intraoperative ablation of liver metastases < 2 cm in size are eligible
- Patients who underwent prior liver resection or ablation for colorectal liver metastases are eligible
Patients previously treated with systemic chemotherapy and/or biologic agents for colorectal cancer are eligible
The primary tumor in the colon or rectum may be intact or resected
Low-volume lung metastases are defined as solid pulmonary nodules < 2 cm with non-spiculated contours, no benign-appearing calcifications, and =< 14 in number, diagnosed by computed tomography of the chest or positron emission tomography (PET)
Lung metastases will be unresectable due to anatomic location, distribution, or patients' comorbidities, as determined by review of imaging by a faculty member in the Department of Thoracic & Cardiovascular Surgery
Patients must sign a study-specific consent form
Patients will undergo CT imaging of the chest, abdomen, and pelvis to evaluate lung and liver metastases within 60 days of registration; for patients who cannot tolerate CT contrast or have hepatic steatosis that reduces the sensitivity of CT, MRI of the liver will be performed

Exclusion Criteria:

Radiographic evidence of disease other than liver and lungs, with the exception of mediastinal lymph nodes < 2 cm and hepatoduodenal ligament lymphadenopathy, diagnosed by computed tomography, magnetic resonance imaging, or positron emission tomography
Serum bilirubin >= 2 mg/dL
Platelet count < 50,000/uL
Eastern Cooperative Oncology Group (ECOG) performance status of 3-4
Patient refusal to participate in randomization
Pregnant women are excluded from this study
Planned stereotactic body radiation therapy (SBRT) for the pulmonary metastases

Sites / Locations

M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Group I (surgery, chemotherapy)

Group II (chemotherapy)

Arm Description

Patients undergo hepatectomy and receive chemotherapy at the discretion of treating oncologist. Patients whose lung tumors become able to be removed by surgery with chemotherapy may undergo lung metastasectomy.

Patients receive chemotherapy at the discretion of the treating oncologist. Patients whose lung tumors become able to be removed by surgery with chemotherapy may undergo lung metastasectomy.

Outcomes

Primary Outcome Measures

Overall survival

The primary analysis will be performed in an intention-to-treat data set. Stratified log-rank test adjusting for the study stratification factors will be used to compare overall survival between the two treatment arms. The hazards ratio of overall survival for the surgery arm compared to the non-surgery arm will be estimated by fitting Cox proportional hazards regression models, adjusting for the effects of covariates including stratification factors.

Secondary Outcome Measures

Incidence of adverse events

Tabulated by frequency and percentages, by grade, and by their relations to surgical treatment.

Extrahepatic and extrapulmonary metastases

The Kaplan-Meier method will be used to estimate time to extrahepatic and extrapulmonary metastases.

Intrahepatic recurrence

The Kaplan-Meier method will be used to estimate time to intrahepatic recurrence among patients randomized to surgery.

Biomarker levels in blood and resected liver specimens

Univariate and multivariate Cox proportional hazards models will be fitted to evaluate the association between biomarkers in blood and resected liver specimens and time to event outcomes, including overall survival development of extrahepatic and extrapulmonary metastases, and time to intrahepatic recurrence among patients randomized to surgery. Univariate and multivariate logistic regression will be used to assess the association between biomarkers and response to chemotherapy

Scores of the Functional Assessment of Cancer Therapy - General 7 questionnaire

Summarized using descriptive statistics including mean, standard deviation, median, and range. Summation of item GP1, GP4, GP2, and GE6 (higher score indicates worse condition) and summation of GF5, GF3 and GF7 (higher score indicates better condition) will be calculated for each patient. Two sample t-tests will be used to compare scores of each item or summations between the two treatment arms.

Patients who abandon treatment

Full Information

NCT ID

NCT02738606

First Posted

April 12, 2016

Last Updated

March 27, 2023

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT02738606

Brief Title

Liver Surgery and Chemotherapy in Treating Patients With Colorectal Cancer With Liver Metastases That Can Be Removed by Surgery and Lung Metastases That Cannot Be Removed by Surgery

Official Title

Randomized Controlled Phase II Trial of Liver Resection Versus No Surgery in Patients With Liver and Unresectable Pulmonary Metastases From Colorectal Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

May 25, 2016 (Actual)

Primary Completion Date

December 31, 2025 (Anticipated)

Study Completion Date

December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This randomized phase II trial studies how well liver surgery and chemotherapy compared to chemotherapy alone work in treating patients with colorectal cancer that has spread to the liver (liver metastases) that can be removed by surgery and that has spread to the lungs (lung metastases) that cannot be removed by surgery. Liver surgery removes a portion of the liver affected by the tumor. Chemotherapy drugs 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. Liver surgery and chemotherapy may work better than chemotherapy alone in treating patients with colorectal cancer which has spread to the liver and lungs.

Detailed Description

PRIMARY OBJECTIVE: I. To determine a survival benefit of liver resection in patients with resectable liver and unresectable low-volume pulmonary metastases from colorectal cancer. SECONDARY OBJECTIVES: I. To identify biomarkers in blood and resected liver specimens that correlate with survival, and development of extrahepatic and extrapulmonary metastases. II. To assess patients' quality-of-life in each treatment arm with serial questionnaires. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients undergo hepatectomy and receive chemotherapy at the discretion of treating oncologist. Patients whose lung tumors become able to be removed by surgery with chemotherapy may undergo lung metastasectomy. GROUP II: Patients receive chemotherapy at the discretion of the treating oncologist. Patients whose lung tumors become able to be removed by surgery with chemotherapy may undergo lung metastasectomy. Patients are followed up every 3-6 months up to 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Colorectal Carcinoma, Metastatic Malignant Neoplasm in the Liver, Metastatic Malignant Neoplasm in the Lung, Recurrent Colorectal Carcinoma, Resectable Colorectal Carcinoma, Stage IV Colorectal Cancer AJCC v7, Stage IVA Colorectal Cancer AJCC v7, Stage IVB Colorectal Cancer AJCC v7

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

29 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group I (surgery, chemotherapy)

Arm Type

Experimental

Arm Description

Arm Title

Group II (chemotherapy)

Arm Type

Active Comparator

Arm Description

Patients receive chemotherapy at the discretion of the treating oncologist. Patients whose lung tumors become able to be removed by surgery with chemotherapy may undergo lung metastasectomy.

Intervention Type

Drug

Intervention Name(s)

Chemotherapy

Other Intervention Name(s)

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

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Procedure

Intervention Name(s)

Metastasectomy

Intervention Description

Undergo lung metastasectomy

Intervention Type

Other

Intervention Name(s)

Quality-of-Life Assessment

Other Intervention Name(s)

Quality of Life Assessment

Intervention Description

Ancillary studies

Intervention Type

Procedure

Intervention Name(s)

Therapeutic Conventional Surgery

Intervention Description

Undergo hepatectomy

Primary Outcome Measure Information:

Title

Overall survival

Description

Time Frame

From the date of randomization to the date of death or the date of last follow-up, assessed up to 3 years

Secondary Outcome Measure Information:

Title

Incidence of adverse events

Description

Tabulated by frequency and percentages, by grade, and by their relations to surgical treatment.

Time Frame

Up to 3 years

Title

Extrahepatic and extrapulmonary metastases

Description

The Kaplan-Meier method will be used to estimate time to extrahepatic and extrapulmonary metastases.

Time Frame

Up to 3 years

Title

Intrahepatic recurrence

Description

The Kaplan-Meier method will be used to estimate time to intrahepatic recurrence among patients randomized to surgery.

Time Frame

Up to 3 years

Title

Biomarker levels in blood and resected liver specimens

Description

Time Frame

Up to 3 years

Title

Scores of the Functional Assessment of Cancer Therapy - General 7 questionnaire

Description

Time Frame

Up to 3 years

Title

Patients who abandon treatment

Time Frame

Up to 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with synchronous or metachronous diagnosis of resectable liver metastases by computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen Patients requiring percutaneous or intraoperative ablation of liver metastases < 2 cm in size are eligible Patients who underwent prior liver resection or ablation for colorectal liver metastases are eligible Patients previously treated with systemic chemotherapy and/or biologic agents for colorectal cancer are eligible The primary tumor in the colon or rectum may be intact or resected Low-volume lung metastases are defined as solid pulmonary nodules < 2 cm with non-spiculated contours, no benign-appearing calcifications, and =< 14 in number, diagnosed by computed tomography of the chest or positron emission tomography (PET) Lung metastases will be unresectable due to anatomic location, distribution, or patients' comorbidities, as determined by review of imaging by a faculty member in the Department of Thoracic & Cardiovascular Surgery Patients must sign a study-specific consent form Patients will undergo CT imaging of the chest, abdomen, and pelvis to evaluate lung and liver metastases within 60 days of registration; for patients who cannot tolerate CT contrast or have hepatic steatosis that reduces the sensitivity of CT, MRI of the liver will be performed Exclusion Criteria: Radiographic evidence of disease other than liver and lungs, with the exception of mediastinal lymph nodes < 2 cm and hepatoduodenal ligament lymphadenopathy, diagnosed by computed tomography, magnetic resonance imaging, or positron emission tomography Serum bilirubin >= 2 mg/dL Platelet count < 50,000/uL Eastern Cooperative Oncology Group (ECOG) performance status of 3-4 Patient refusal to participate in randomization Pregnant women are excluded from this study Planned stereotactic body radiation therapy (SBRT) for the pulmonary metastases

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yun S Chun

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

M D Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

MD Anderson Cancer Center

Learn more about this trial

Liver Surgery and Chemotherapy in Treating Patients With Colorectal Cancer With Liver Metastases That Can Be Removed by Surgery and Lung Metastases That Cannot Be Removed by Surgery

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