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

Sponsor

Southwest Oncology Group (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00118105

Collaborator

National Cancer Institute (NCI) (NIH), Eastern Cooperative Oncology Group (Other)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Metastatic Cancer	Biological: bevacizumab Drug: capecitabine Drug: oxaliplatin Procedure: conventional surgery	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2006

Actual Primary Completion Date :

Apr 1, 2007

Actual Study Completion Date :

Apr 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemotherapy + Surgery + Chemotherapy Preoperative 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	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 Other Names: Avastin NSC-704865 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 Other Names: Xeloda NSC-712807 Drug: oxaliplatin 130 mg/m^2, IV, Day 1 of cycles 1,2,3,4 Other Names: NSC-266046 Procedure: conventional surgery Resection

Arm

Intervention/Treatment

Experimental: Chemotherapy + Surgery + Chemotherapy

Preoperative 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

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

Other Names:

Avastin

NSC-704865

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

Other Names:

Xeloda

NSC-712807

Drug: oxaliplatin

130 mg/m^2, IV, Day 1 of cycles 1,2,3,4

Other Names:

NSC-266046

Procedure: conventional surgery

Resection

Outcome Measures

Primary Outcome Measures

Proportion of patients with R0 resection after treatment [16-18 weeks from registration]
Probability of nonprogression (i.e., stable disease or response [complete and partial, confirmed and unconfirmed]) [12 weeks from registration]
Comparison of patients achieving R0 resection with literature [16-18 weeks from registration]
Overall survival [Up to 3 years]
Disease-free survival [Up to 3 years]
Positron emission tomography response [Registration and 12 weeks]
Correlation of clinical outcome with expression of biomarkers and telomere length [Up to 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
2	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60507
3	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
4	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
5	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
6	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
7	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
8	Reid Hospital & Health Care Services, Incorporated	Richmond	Indiana	United States	47374
9	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas	United States	67401
10	Cancer Research Center at Boston Medical Center	Boston	Massachusetts	United States	02118
11	Borgess Medical Center	Kalamazooaa	Michigan	United States	49001
12	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
13	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
14	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
15	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
16	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
17	St. Vincent Healthcare	Billings	Montana	United States	59101
18	Billings Clinic Cancer Center	Billings	Montana	United States	59107-5100
19	Deaconess Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
20	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
21	St. James Community Hospital	Butte	Montana	United States	59701
22	Frontier Cancer Center	Great Falls	Montana	United States	59405
23	Great Falls Clinic	Great Falls	Montana	United States	59405
24	St. Peter's Hospital	Helena	Montana	United States	59601
25	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
26	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
27	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
28	Community Medical Center	Missoula	Montana	United States	59801
29	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
30	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
31	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
32	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
33	Grandview Hospital	Dayton	Ohio	United States	45405
34	Good Samaritan Hospital	Dayton	Ohio	United States	45406
35	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
36	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
37	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
38	CCOP - Dayton	Dayton	Ohio	United States	45429
39	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
40	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
41	St. Rita's Medical Center	Lima	Ohio	United States	45801
42	Middletown Regional Hospital	Middletown	Ohio	United States	45044
43	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
44	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
45	Danville Regional Medical Center	Danville	Virginia	United States	24541
46	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801