Capecitabine, Cetuximab, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic or Recurrent Colorectal Cancer That Cannot Be Removed By Surgery

NCT00290615 | Completed Phase 2 Results DMC

• 2 other identifiers: Pro00007431 (CDR0000449945)DUMC-7118-05-4R0
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as cetuximab and 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. Cetuximab and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving capecitabine together with cetuximab, oxaliplatin, and bevacizumab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving capecitabine together with cetuximab, oxaliplatin, and bevacizumab works in treating patients with metastatic or recurrent colorectal cancer that cannot be removed by surgery.

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 (3)

• Safety and Tolerability

  After all participants went off study drug regimine.

• Progression-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.

Other Outcomes (2)

• Effect on Angiogenesis Biomarkers

  After study completion

• Effect on Wound Angiogenesis

  After study completion

Study Arms (1)

Capecitabine, Oxaliplatin, Bevacizumab, Cetuximab

EXPERIMENTAL

Capecitabine - oral administration of 850 mg/m2 every 12 hours on days 1-14. Oxaliplatin - IV administration of 130 mg/m2 over 2 hours on day 1 of a cycle. Bevacizumab- IV administration of 7.5 mg/kg over 30-90 minutes on day 1 of a cycle. Cetuximab at an initial dose of 400 mg/m2 over 120 minutes and subsequently 250 mg/m2 over 60 minutes on day 1 of a cycle. Cycles are 21 days.

Biological: bevacizumab; Biological: cetuximab; Drug: capecitabine; Drug: oxaliplatin

Interventions

bevacizumab BIOLOGICAL

Also known as: Avastin

Capecitabine, Oxaliplatin, Bevacizumab, Cetuximab

cetuximab BIOLOGICAL

Capecitabine, Oxaliplatin, Bevacizumab, Cetuximab

capecitabine DRUG

Capecitabine, Oxaliplatin, Bevacizumab, Cetuximab

oxaliplatin DRUG

Capecitabine, Oxaliplatin, Bevacizumab, Cetuximab

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the colon or rectum * Unresectable disease * Metastatic or recurrent disease * Not amenable to potentially curative treatment * No untreated leptomeningeal or brain metastases PATIENT CHARACTERISTICS: Performance status * ECOG 0-2 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 2,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 * No known uncontrolled coagulopathy Hepatic * AST and ALT \< 2.5 times upper limits of normal (ULN) (5 times ULN if liver metastases are present) * Bilirubin \< 2.0 times ULN Renal * Creatinine clearance \> 40 mL/min * Urine protein negative * Urine protein:creatinine ratio \> 1 Cardiovascular * No unstable or uncontrolled hypertension (i.e., blood pressure \[BP\] \> 150/100 mm Hg despite antihypertensive therapy) * Patients who recently started or have adjusted antihypertensive medications are eligible provided BP is \< 140/90 mm Hg for ≥ 3 different measurements over 14 days * No arterial thromboembolic events within the past 6 months, including any of the following: * Transient ischemic attack * Cerebrovascular accident * Unstable angina * Myocardial infarction * Clinically significant peripheral vascular disease * No New York Heart Association class III-IV congestive heart failure * No uncontrolled symptomatic coronary artery disease or cardiac arrhythmia * No other significant uncontrolled cardiac disease Gastrointestinal * No lack of physical integrity of the upper gastrointestinal tract * No malabsorption syndrome * No inability to tolerate oral medication Immunologic * No prior severe infusion reaction to a monoclonal antibody * No history of an allergic reaction attributed to compounds of similar chemical or biologic composition to oxaliplatin, cetuximab, capecitabine, or bevacizumab * No prior unanticipated, severe reaction to fluoropyrimidine therapy or known hypersensitivity to fluoroucacil Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during the study and for 3-4 months after completion of study treatment * No peripheral neuropathy ≥ grade 2 * No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix * No known dihydropyrimidine dehydrogenase deficiency PRIOR CONCURRENT THERAPY: Biologic therapy * No prior adjuvant bevacizumab or cetuximab * No other concurrent anticancer immunotherapy or biologic therapy Chemotherapy * At least 6 months since a prior adjuvant fluorouracil-, leucovorin calcium-, or capecitabine-based regimen * At least 12 months since prior adjuvant oxaliplatin * No prior chemotherapy for metastatic or recurrent disease Endocrine therapy * No concurrent hormonal therapy Radiotherapy * No concurrent radiotherapy Surgery * More than 4 weeks since prior major surgery and recovered * More than 6 months since vascular surgery, stenting, or angioplasty Other * At least 4 weeks since prior and no concurrent sorivudine or brivudine * More than 4 weeks since prior participation in any investigational drug study * No prior therapy that affects or targets the epidermal growth factor pathway * No concurrent cimetidine * Concurrent ranitidine, famotidine, or proton-pump inhibitors allowed * Concurrent anticoagulation therapy with full-dose anticoagulant allowed provided dose is stable for at least 2 weeks

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

Sponsors & Collaborators

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

Study Sites (2)

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Related Publications (1)

• Wong NS, Fernando NH, Nixon AB, Cushman S, Aklilu M, Bendell JC, Morse MA, Blobe GC, Ashton J, Pang H, Hurwitz HI. A phase II study of capecitabine, oxaliplatin, bevacizumab and cetuximab in the treatment of metastatic colorectal cancer. Anticancer Res. 2011 Jan;31(1):255-61.

  PMID: 21273607 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Cetuximab; Capecitabine; Oxaliplatin

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; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

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

  STUDY CHAIR

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: February 9, 2006
• First Posted: February 13, 2006
• Study Start: January 1, 2006
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2011
• Last Updated: May 7, 2013
• Results First Posted: May 7, 2013

Record last verified: 2013-03

Locations

US (2)