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

Colorectal Cancer Clinical Trial

Official title:

A Phase II Trial of Neoadjuvant Capecitabine, Oxaliplatin, and Bevacizumab for Resectable Colorectal Metastases in the Liver

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00118105
• Other study ID #: CDR0000433491
• Secondary ID: S0408U10CA032102
• Status: Withdrawn
• Phase: Phase 2
• First received: July 8, 2005
• Last updated: January 2, 2013
• Start date: November 2006
• Est. completion date: April 2007

Study information

• Verified date: January 2013
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2007
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of hepatic metastases secondary to colorectal cancer by percutaneous hepatic biopsy

• Resectable hepatic metastases by any of the following:

• Minor resection (i.e., less than a hemihepatectomy)

• Major resection (i.e., hemihepatectomy or extended hepatectomy)

• Bilobar resection (including atypical resection)

• Synchronous primary tumor and hepatic metastases allowed

• Radiologic evidence of hepatic metastases by multiphasic contrast-enhanced spiral CT scan

• Resectable primary colorectal cancer that is in place allowed

• Measurable disease

• No evidence of extrahepatic metastases by chest x-ray or CT scan of the chest

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin = 9.0 g/dL

• WBC = 3,000/mm^3

• Platelet count = 100,000/mm^3

• Absolute neutrophil count = 1,500/mm^3

Hepatic

• Bilirubin = 2 times upper limit of normal (ULN)

• SGOT or SGPT = 2.5 times ULN

Renal

• Creatinine clearance = 60 mL/min

• Urine protein/creatinine ratio < 1 OR

• Urine protein < 1 g by 24-hour urine collection

Cardiovascular

• No uncontrolled hypertension (i.e., blood pressure > 150/90 mm Hg)

• History of hypertension allowed provided it is well controlled on a stable regimen of anti-hypertensive therapy

• No arterial thromboembolic event within the past 12 months, including any of the following:

• Transient ischemic attack

• Cerebrovascular accident

• Unstable angina

• Myocardial infarction

• No peripheral vascular disease = grade 2

Other

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No pre-existing peripheral neuropathy = grade 2

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 6 months since prior adjuvant chemotherapy for the primary tumor

• No prior systemic chemotherapy for metastatic disease

• No prior hepatic artery infusion chemotherapy for metastatic disease

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for metastatic disease

Surgery

• More than 7 days since prior colonoscopy or fine needle aspiration

• More than 28 days since prior major invasive surgery or open biopsy

Other

• At least 4 weeks since prior and no concurrent sorivudine or brivudine

• No prior radiofrequency ablation for metastatic disease

• No prior cryotherapy for metastatic disease

• No other prior ablative techniques for metastatic disease

• No concurrent cimetidine

• Concurrent ranitidine or other drug from a different antiulcer class allowed

• No concurrent oral anticoagulation for treatment of thrombosis

• Concurrent warfarin (1 mg) to maintain patency of central venous catheter allowed

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Biological:
• bevacizumab
Preoperative: 7.5 mg/kg, IV, Day 1 of cycles 1,2,3 Postoperative: 7.5 mg/kg, IV, Day 1 of cycles 1,2,3,4

Drug:
• capecitabine
Pre & Post Operative: 1,700 mg/m^2/day, PO at 12 hr interval, Days 1-14 of cycles 1,2,3,4
• oxaliplatin
130 mg/m^2, IV, Day 1 of cycles 1,2,3,4

Procedure:
• conventional surgery
Resection

Locations

Country	Name	City	State
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	Billings Clinic Cancer Center	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Deaconess Billings Clinic - Downtown	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare	Billings	Montana
United States	Cancer Research Center at Boston Medical Center	Boston	Massachusetts
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	St. James Community Hospital	Butte	Montana
United States	Danville Regional Medical Center	Danville	Virginia
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Frontier Cancer Center	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Borgess Medical Center	Kalamazooaa	Michigan
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	St. Rita's Medical Center	Lima	Ohio
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Middletown Regional Hospital	Middletown	Ohio
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	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Reid Hospital & Health Care Services, Incorporated	Richmond	Indiana
United States	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Southwest Oncology Group	Eastern Cooperative Oncology Group, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Abdalla EK, Eng C, Madary A, Vauthey JN; Southwest Oncology Group 0408. Southwest Oncology Group 0408: Phase II trial of neoadjuvant capecitabine/oxaliplatin/bevacizumab for resectable colorectal metastases in the liver. Clin Colorectal Cancer. 2006 Mar;5(6):436-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with R0 resection after treatment		16-18 weeks from registration	No
Primary	Probability of nonprogression (i.e., stable disease or response [complete and partial, confirmed and unconfirmed])		12 weeks from registration	No
Primary	Comparison of patients achieving R0 resection with literature		16-18 weeks from registration	No
Primary	Overall survival		Up to 3 years	No
Primary	Disease-free survival		Up to 3 years	No
Primary	Positron emission tomography response		Registration and 12 weeks	No
Primary	Correlation of clinical outcome with expression of biomarkers and telomere length		Up to 3 years	No