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

This study has been withdrawn prior to enrollment.
(Budget Constraints)
Sponsor:
Collaborators:
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00118105
First received: July 8, 2005
Last updated: January 2, 2013
Last verified: January 2013
  Purpose

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 Intervention Phase
Colorectal Cancer
Metastatic Cancer
Biological: bevacizumab
Drug: capecitabine
Drug: oxaliplatin
Procedure: conventional surgery
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Neoadjuvant Capecitabine, Oxaliplatin, and Bevacizumab for Resectable Colorectal Metastases in the Liver

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

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

Enrollment: 0
Study Start Date: November 2006
Study Completion Date: April 2007
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: NSC-266046
Procedure: conventional surgery
Resection

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00118105

  Show 46 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Eastern Cooperative Oncology Group
Investigators
Principal Investigator: Jean-Nicolas Vauthey, MD M.D. Anderson Cancer Center
Principal Investigator: Robert de W. Marsh, MD University of Florida
Principal Investigator: Cathy Eng, MD M.D. Anderson Cancer Center
Principal Investigator: Henry Q. Xiong, MD, PhD M.D. Anderson Cancer Center
Principal Investigator: Kevin G. Billingsley, MD OHSU Knight Cancer Institute
Principal Investigator: Steven A. Curley, MD M.D. Anderson Cancer Center
  More Information

Publications:
Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00118105     History of Changes
Other Study ID Numbers: CDR0000433491, S0408, U10CA032102
Study First Received: July 8, 2005
Last Updated: January 2, 2013
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
liver metastases

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Rectal Diseases
Bevacizumab
Capecitabine
Fluorouracil
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014