Capecitabine, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic or Recurrent Colorectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Herbert Hurwitz, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00416494
First received: December 27, 2006
Last updated: April 8, 2014
Last verified: April 2014
  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 find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving capecitabine and oxaliplatin together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving oxaliplatin and capecitabine together with bevacizumab works in treating patients with metastatic or recurrent colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Biological: bevacizumab
Drug: oxaliplatin
Drug: Capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Oxaliplatin, Capecitabine and Bevacizumab in the Treatment of Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Response Rate (Percentage of Participants With Partial or Complete Response) [ Time Frame: After all subjects were evaluated for restaging which occured every 9 weeks from drug initiation until disease progression, assesed up to 24 months. ] [ Designated as safety issue: No ]

    Restaging scans occurred every 9 weeks from time of study drug initiation until disease progression.

    Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines.

    The definitions were:

    Complete response (CR)- Disappearance of all target lesions Partial response (PD)- At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Stable disease (SD)- Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions



Secondary Outcome Measures:
  • Time to Progression [ Time Frame: From time of treatment until documented progression, assesed up to 60 months. ] [ Designated as safety issue: No ]

    Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines.

    Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.


  • Disease Free Survival [ Time Frame: From time of treatment until documented progression or death from any cause, whichever came first, assesed up to 60 months. ] [ Designated as safety issue: No ]

    Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines.

    Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.


  • Overall Survival [ Time Frame: From time of treatment until death from any cause, assesed up to 60 months. ] [ Designated as safety issue: No ]
    Average months of survival of participants after receiving study drug.

  • Safety and Tolerability [ Time Frame: After all participants went off study drug regimine. ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events


Other Outcome Measures:
  • Effect on Angiogenesis Biomarkers [ Time Frame: After study completion ] [ Designated as safety issue: No ]
  • Effect on Wound Angiogenesis [ Time Frame: After study completion ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: September 2003
Estimated Study Completion Date: January 2016
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Initial Cohort Biological: bevacizumab
10 mg/kg intravenously over 30-90 minutes on day 1
Drug: oxaliplatin
85 mg/m2 intravenously over 2 hours on day 1.
Drug: Capecitabine
Oral administration every 12 hours on days 1-5 and 8-12 1000 mg/m2 in initial cohort
Experimental: Second cohort Biological: bevacizumab
10 mg/kg intravenously over 30-90 minutes on day 1
Drug: oxaliplatin
85 mg/m2 intravenously over 2 hours on day 1.
Drug: Capecitabine
Oral administration every 12 hours on days 1-5 and 8-12 850 mg/m2 in second cohort

Detailed Description:

OBJECTIVES:

Primary

  • Evaluate the response rate in patients with previously untreated metastatic colorectal cancer treated with capecitabine, oxaliplatin, and bevacizumab.

Secondary

  • Assess time to progression (TTP), disease-free survival (DFS), and overall survival (OS) in patients treated with this regimen.
  • Assess the safety and tolerability of bevacizumab, oxaliplatin, and capecitabine in patients with previously untreated metastatic colorectal cancer.

Exploratory

  • Evaluate the effect of this regimen on the biomarkers of angiogenesis.
  • Assess the effect of this regimen on wound angiogenesis.

OUTLINE: Patients receive oral capecitabine twice daily on days 1-5 and 8-12, oxaliplatin IV over 2 hours on day 1, and bevacizumab IV over 1-1½ hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 50 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:

  • Histologically documented adenocarcinoma of the colon or rectum

    • Metastatic or recurrent disease not amenable to potentially curative treatment (e.g., inoperable metastatic disease)
  • No leptomeningeal or brain metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 2,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • AST/ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if known liver metastases)
  • Bilirubin < 1.5 times ULN
  • Creatinine clearance > 50 mL/min
  • No unstable or poorly controlled hypertension (> 150/100 mm Hg)

    • Patients who have recently started or adjusted antihypertensive medications are eligible provided blood pressure is < 140/90 mm Hg on any new regimen for at least 3 different observations over 14 days
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during study and for at least 3-4 months after study completion
  • No arterial or venous thrombosis (including cerebrovascular accident) within the last 3 months
  • No known, existing, uncontrolled coagulopathy
  • No clinically significant cardiac disease
  • No congestive heart failure
  • No symptomatic coronary artery disease
  • No cardiac arrhythmias not well controlled with medication
  • No myocardial infarction within the last 12 months
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to oxaliplatin, capecitabine, or bevacizumab
  • No history of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the patient at high risk from treatment complications

PRIOR CONCURRENT THERAPY:

  • At least 4 weeks since prior sorivudine or brivudine
  • At least 6 months since prior adjuvant treatment with fluorouracil and leucovorin calcium or a fluorouracil and leucovorin calcium-based regimen
  • No major surgery within 4 weeks without complete recovery
  • No prior chemotherapy for metastatic/recurrent disease
  • No cancer immunotherapy or other biologic therapy while on therapy
  • No radiotherapy while on study
  • No hormonal therapy for cancer while on study
  • No full-dose warfarin (INR of > 1.5), heparin (> 10,000 units/day), or thrombolytic agents
  • Allopurinol and cimetidine should be discontinued prior to starting on this regimen
  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: NCT00416494

Sponsors and Collaborators
Herbert Hurwitz, MD
Investigators
Principal Investigator: Herbert I. Hurwitz, MD Duke Cancer Institute
  More Information

Additional Information:
Publications:
Hurwitz H, Fernando N, Yu D, et al.: A phase II study of oxaliplatin, capecitabine and bevacizumab in the treatment of metastatic colorectal cancer. [Abstract] Ann Oncol 16 (Suppl 2): A-55P, ii285, 2005.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Herbert Hurwitz, MD, Associate Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00416494     History of Changes
Other Study ID Numbers: Pro00008646, DUMC-4951-05-7R2, GENENTECH-DUMC-4951-05-7R2, SANOFI-DUMC-4951-05-7R2, ROCHE-DUMC-4951-05-7R2, CDR0000449971
Study First Received: December 27, 2006
Results First Received: February 12, 2013
Last Updated: April 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
adenocarcinoma of the colon
recurrent colon cancer
stage IV colon cancer
adenocarcinoma of the rectum
recurrent rectal cancer
stage IV rectal cancer

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

ClinicalTrials.gov processed this record on July 24, 2014