Clinical trial NCT00118105: S0408: Capecitabine, Oxaliplatin, and Bevacizumab in Pts Undergoing Surgery for Liver Mets From Colorectal Cancer
Official title: A Phase II Trial of Neoadjuvant Capecitabine, Oxaliplatin, and Bevacizumab for Resectable Colorectal Metastases in the Liver
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Colorectal Cancer
Metastatic Cancer
Keywords: recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
liver metastases
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Eastern Cooperative Oncology Group
First posted: 2005-07-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients with R0 resection after treatment
timeFrame: 16-18 weeks from registration
measure: Probability of nonprogression (i.e., stable disease or response [complete and partial, confirmed and unconfirmed])
timeFrame: 12 weeks from registration
measure: Comparison of patients achieving R0 resection with literature
timeFrame: 16-18 weeks from registration
measure: Overall survival
timeFrame: Up to 3 years
measure: Disease-free survival
timeFrame: Up to 3 years
measure: Positron emission tomography response
timeFrame: Registration and 12 weeks
measure: Correlation of clinical outcome with expression of biomarkers and telomere length
timeFrame: Up to 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Limited - West
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center at Carle Foundation Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services, Incorporated
state: Indiana
city: Salina
country: United States
facility: Tammy Walker Cancer Center at Salina Regional Health Center
state: Kansas
city: Boston
country: United States
facility: Cancer Research Center at Boston Medical Center
state: Massachusetts
city: Kalamazooaa
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare
state: Montana
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Billings
country: United States
facility: Deaconess Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Butte
country: United States
facility: St. James Community Hospital
state: Montana
city: Great Falls
country: United States
facility: Frontier Cancer Center
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology, PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Missoula
country: United States
facility: Guardian Oncology and Center for Wellness
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Lima
country: United States
facility: St. Rita's Medical Center
state: Ohio
city: Middletown
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Sheridan
country: United States
facility: Welch Cancer Center at Sheridan Memorial Hospital
state: Wyoming
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Jean-Nicolas Vauthey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Florida
name: Robert de W. Marsh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Cathy Eng, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Henry Q. Xiong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: OHSU Knight Cancer Institute
name: Kevin G. Billingsley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Steven A. Curley, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.3816/ccc.2006.n.015. No abstract available.