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S0408: Capecitabine, Oxaliplatin, and Bevacizumab in Pts Undergoing Surgery for Liver Mets From Colorectal Cancer

Phase 2
Withdrawn
Conditions
Colorectal Cancer
Metastatic Cancer
Interventions
Biological: bevacizumab
Procedure: conventional surgery
Registration Number
NCT00118105
Lead Sponsor
SWOG Cancer Research Network
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving capecitabine and oxaliplatin together with bevacizumab before and after surgery may be an effective treatment for liver metastases.

PURPOSE: This phase II trial is studying how well giving capecitabine and oxaliplatin together with bevacizumab works in treating patients who are undergoing surgery for liver metastases due to colorectal cancer.

Detailed Description

OBJECTIVES:

* Determine the proportion of patients with resectable hepatic metastases secondary to colorectal cancer who undergo surgical resection and achieve a R0 resection after treatment with neoadjuvant capecitabine, oxaliplatin, and bevacizumab.

* Determine the probability of non-progression (i.e., stable disease or response \[complete and partial, confirmed and unconfirmed\]) in patients treated with this regimen.

* Compare the proportion of patients treated with this regimen who undergo surgical resection and those who achieve a R0 resection with that described in the literature.

* Determine overall survival and disease-free survival of patients treated with this regimen.

* Determine response by positron emission tomography in patients treated with this regimen.

* Correlate clinical outcome with expression of biomarkers (e.g., thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, excision repair cross complementing 1, and hTERT) and telomere length in patients treated with this regimen.

OUTLINE: This is a multicenter study.

* Neoadjuvant therapy: Patients receive bevacizumab\* IV over 30-90 minutes and oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

NOTE: \*Bevacizumab is administered during courses 1-3 of neoadjuvant therapy.

* Surgery: Approximately 3-4 weeks after completion of neoadjuvant therapy, patients are evaluated. Patients with unresectable disease are removed from the study. Patients with resectable disease undergo surgical resection of liver metastases within 4-6 weeks after completion of neoadjuvant therapy.

* Adjuvant therapy: Beginning at least 28 days after surgical resection, patients with at least stable disease after completion of neoadjuvant therapy receive 4 courses of adjuvant bevacizumab\*\*, oxaliplatin, and capecitabine as in neoadjuvant therapy.

NOTE: \*\*Bevacizumab is administered during courses 1-4 of adjuvant therapy.

After completion of study treatment, patients are followed every 4 months until disease progression and then every 6 months for up to 3 years from study entry.

PROJECTED ACCRUAL: Approximately 35-65 patients will be accrued for this study.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Chemotherapy + Surgery + ChemotherapybevacizumabPreoperative Neoadjuvant Chemotherapy * Bevacizumab, 7.5 mg/kg, IV, Day 1 of cycles 1,2,3 * Oxaliplatin, 130 mg/m\^2, IV, Day 1 of cycles 1,2,3,4 * Capecitabine, 1,700 mg/m\^2/day divided, PO at 12 hr intervals, Days 1-14 of cycles 1,2,3,4 Conventional surgery: After 4 cycles of chemotherapy Postoperative Neoadjuvant Chemotherapy * Bevacizumab, 7.5 mg/kg, IV, Day 1 of cycles 1,2,3,4 * Oxaliplatin, 130 mg/m\^2, IV, Day 1 of cycles 1,2,3,4 * Capecitabine, 1,700 mg/m\^2/day divided, PO at 12 hr intervals, Days 1-14 of cycles 1,2,3,4
Chemotherapy + Surgery + Chemotherapyconventional surgeryPreoperative Neoadjuvant Chemotherapy * Bevacizumab, 7.5 mg/kg, IV, Day 1 of cycles 1,2,3 * Oxaliplatin, 130 mg/m\^2, IV, Day 1 of cycles 1,2,3,4 * Capecitabine, 1,700 mg/m\^2/day divided, PO at 12 hr intervals, Days 1-14 of cycles 1,2,3,4 Conventional surgery: After 4 cycles of chemotherapy Postoperative Neoadjuvant Chemotherapy * Bevacizumab, 7.5 mg/kg, IV, Day 1 of cycles 1,2,3,4 * Oxaliplatin, 130 mg/m\^2, IV, Day 1 of cycles 1,2,3,4 * Capecitabine, 1,700 mg/m\^2/day divided, PO at 12 hr intervals, Days 1-14 of cycles 1,2,3,4
Chemotherapy + Surgery + ChemotherapycapecitabinePreoperative Neoadjuvant Chemotherapy * Bevacizumab, 7.5 mg/kg, IV, Day 1 of cycles 1,2,3 * Oxaliplatin, 130 mg/m\^2, IV, Day 1 of cycles 1,2,3,4 * Capecitabine, 1,700 mg/m\^2/day divided, PO at 12 hr intervals, Days 1-14 of cycles 1,2,3,4 Conventional surgery: After 4 cycles of chemotherapy Postoperative Neoadjuvant Chemotherapy * Bevacizumab, 7.5 mg/kg, IV, Day 1 of cycles 1,2,3,4 * Oxaliplatin, 130 mg/m\^2, IV, Day 1 of cycles 1,2,3,4 * Capecitabine, 1,700 mg/m\^2/day divided, PO at 12 hr intervals, Days 1-14 of cycles 1,2,3,4
Chemotherapy + Surgery + ChemotherapyoxaliplatinPreoperative Neoadjuvant Chemotherapy * Bevacizumab, 7.5 mg/kg, IV, Day 1 of cycles 1,2,3 * Oxaliplatin, 130 mg/m\^2, IV, Day 1 of cycles 1,2,3,4 * Capecitabine, 1,700 mg/m\^2/day divided, PO at 12 hr intervals, Days 1-14 of cycles 1,2,3,4 Conventional surgery: After 4 cycles of chemotherapy Postoperative Neoadjuvant Chemotherapy * Bevacizumab, 7.5 mg/kg, IV, Day 1 of cycles 1,2,3,4 * Oxaliplatin, 130 mg/m\^2, IV, Day 1 of cycles 1,2,3,4 * Capecitabine, 1,700 mg/m\^2/day divided, PO at 12 hr intervals, Days 1-14 of cycles 1,2,3,4
Primary Outcome Measures
NameTimeMethod
Proportion of patients with R0 resection after treatment16-18 weeks from registration
Comparison of patients achieving R0 resection with literature16-18 weeks from registration
Overall survivalUp to 3 years
Probability of nonprogression (i.e., stable disease or response [complete and partial, confirmed and unconfirmed])12 weeks from registration
Disease-free survivalUp to 3 years
Positron emission tomography responseRegistration and 12 weeks
Correlation of clinical outcome with expression of biomarkers and telomere lengthUp to 3 years
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (46)

USC/Norris Comprehensive Cancer Center and Hospital

🇺🇸

Los Angeles, California, United States

Rush-Copley Cancer Care Center

🇺🇸

Aurora, Illinois, United States

Cancer Research Center at Boston Medical Center

🇺🇸

Boston, Massachusetts, United States

West Michigan Cancer Center

🇺🇸

Kalamazoo, Michigan, United States

Bronson Methodist Hospital

🇺🇸

Kalamazoo, Michigan, United States

St. James Community Hospital

🇺🇸

Butte, Montana, United States

Frontier Cancer Center

🇺🇸

Great Falls, Montana, United States

Glacier Oncology, PLLC

🇺🇸

Kalispell, Montana, United States

Kalispell Medical Oncology

🇺🇸

Kalispell, Montana, United States

Community Medical Center

🇺🇸

Missoula, Montana, United States

Guardian Oncology and Center for Wellness

🇺🇸

Missoula, Montana, United States

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center

🇺🇸

Missoula, Montana, United States

Charles F. Kettering Memorial Hospital

🇺🇸

Kettering, Ohio, United States

UVMC Cancer Care Center at Upper Valley Medical Center

🇺🇸

Troy, Ohio, United States

Billings Clinic Cancer Center

🇺🇸

Billings, Montana, United States

Hematology-Oncology Centers of the Northern Rockies - Billings

🇺🇸

Billings, Montana, United States

Welch Cancer Center at Sheridan Memorial Hospital

🇺🇸

Sheridan, Wyoming, United States

Tammy Walker Cancer Center at Salina Regional Health Center

🇺🇸

Salina, Kansas, United States

Joliet Oncology-Hematology Associates, Limited - West

🇺🇸

Joliet, Illinois, United States

Carle Cancer Center at Carle Foundation Hospital

🇺🇸

Urbana, Illinois, United States

CCOP - Carle Cancer Center

🇺🇸

Urbana, Illinois, United States

Saint Anthony Memorial Health Centers

🇺🇸

Michigan City, Indiana, United States

St. Francis Hospital and Health Centers - Beech Grove Campus

🇺🇸

Beech Grove, Indiana, United States

Reid Hospital & Health Care Services, Incorporated

🇺🇸

Richmond, Indiana, United States

Borgess Medical Center

🇺🇸

Kalamazooaa, Michigan, United States

CCOP - Montana Cancer Consortium

🇺🇸

Billings, Montana, United States

Northern Rockies Radiation Oncology Center

🇺🇸

Billings, Montana, United States

St. Vincent Healthcare

🇺🇸

Billings, Montana, United States

Deaconess Billings Clinic - Downtown

🇺🇸

Billings, Montana, United States

Bozeman Deaconess Cancer Center

🇺🇸

Bozeman, Montana, United States

St. Peter's Hospital

🇺🇸

Helena, Montana, United States

Great Falls Clinic

🇺🇸

Great Falls, Montana, United States

Kalispell Regional Medical Center

🇺🇸

Kalispell, Montana, United States

Montana Cancer Specialists at Montana Cancer Center

🇺🇸

Missoula, Montana, United States

Good Samaritan Hospital

🇺🇸

Dayton, Ohio, United States

Wayne Memorial Hospital, Incorporated

🇺🇸

Goldsboro, North Carolina, United States

Grandview Hospital

🇺🇸

Dayton, Ohio, United States

David L. Rike Cancer Center at Miami Valley Hospital

🇺🇸

Dayton, Ohio, United States

Samaritan North Cancer Care Center

🇺🇸

Dayton, Ohio, United States

Veterans Affairs Medical Center - Dayton

🇺🇸

Dayton, Ohio, United States

CCOP - Dayton

🇺🇸

Dayton, Ohio, United States

Blanchard Valley Medical Associates

🇺🇸

Findlay, Ohio, United States

St. Rita's Medical Center

🇺🇸

Lima, Ohio, United States

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

🇺🇸

Xenia, Ohio, United States

Middletown Regional Hospital

🇺🇸

Middletown, Ohio, United States

Danville Regional Medical Center

🇺🇸

Danville, Virginia, United States

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