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

NCT00416494 | Completed Phase 2 Results

• 6 other identifiers: Pro00008646DUMC-4951-05-7R2GENENTECH-DUMC-4951-05-7R2SANOFI-DUMC-4951-05-7R2ROCHE-DUMC-4951-05-7R2CDR0000449971
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

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 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.

Conditions

Colorectal Cancer

Keywords

adenocarcinoma of the colon; recurrent colon cancer; stage IV colon cancer; adenocarcinoma of the rectum; recurrent rectal cancer; stage IV rectal cancer

Outcome Measures

Primary Outcomes (1)

• Response Rate (Percentage of Participants With Partial or Complete Response)

  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

  After all subjects were evaluated for restaging which occured every 9 weeks from drug initiation until disease progression, assesed up to 24 months.

Secondary Outcomes (4)

• Time to Progression

  From time of treatment until documented progression, assesed up to 60 months.

• Disease Free Survival

  From time of treatment until documented progression or death from any cause, whichever came first, assesed up to 60 months.

• Overall Survival

  From time of treatment until death from any cause, assesed up to 60 months.

• Safety and Tolerability

  After all participants went off study drug regimine.

Other Outcomes (2)

• Effect on Angiogenesis Biomarkers

  After study completion

• Effect on Wound Angiogenesis

  After study completion

Study Arms (2)

Initial Cohort

EXPERIMENTAL

Biological: bevacizumab; Drug: oxaliplatin; Drug: Capecitabine

Second cohort

EXPERIMENTAL

Biological: bevacizumab; Drug: oxaliplatin; Drug: Capecitabine

Interventions

bevacizumab BIOLOGICAL

10 mg/kg intravenously over 30-90 minutes on day 1

Initial Cohort; Second cohort

oxaliplatin DRUG

85 mg/m2 intravenously over 2 hours on day 1.

Initial Cohort; Second cohort

Capecitabine DRUG

Oral administration every 12 hours on days 1-5 and 8-12 1000 mg/m2 in initial cohort

Initial Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Herbert Hurwitz, MD: lead
• National Cancer Institute (NCI): collaborator

Related Publications (2)

• 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.

  RESULT

• Liu Y, Starr MD, Bulusu A, Pang H, Wong NS, Honeycutt W, Amara A, Hurwitz HI, Nixon AB. Correlation of angiogenic biomarker signatures with clinical outcomes in metastatic colorectal cancer patients receiving capecitabine, oxaliplatin, and bevacizumab. Cancer Med. 2013 Apr;2(2):234-42. doi: 10.1002/cam4.71. Epub 2013 Mar 6.

  PMID: 23634291 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Oxaliplatin; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Brant Hamel
• Organization: Duke University Medical Center

brant.hamel@duke.edu

919-68-1861

Study Officials

• Herbert I. Hurwitz, MD

  Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: December 27, 2006
• First Posted: December 28, 2006
• Study Start: September 1, 2003
• Primary Completion: January 1, 2008
• Study Completion: August 1, 2014
• Last Updated: September 3, 2014
• Results First Posted: March 14, 2013

Record last verified: 2014-08