Cetuximab and Bevacizumab as First-Line Therapy Followed By Combination Chemotherapy and Bevacizumab With or Without Cetuximab as Second-Line Therapy in Treating Patients With Stage IV Colorectal Cancer

NCT00571740 | Withdrawn Phase 2

• 3 other identifiers: N0548CDR0000578111NCI-2009-00651
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibodies together with combination chemotherapy may kill more tumor cells. PURPOSE: This randomized phase II trial is studying how well giving cetuximab together bevacizumab works as first-line therapy, followed by combination chemotherapy and bevacizumab with or without cetuximab as second-line therapy in treating patients with stage IV colorectal cancer.

Conditions

Colorectal Cancer

Keywords

stage IV colon cancer; stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) rate at 6 months

  at 6 months

Secondary Outcomes (4)

• Tumor response rate associated with second-line therapy

  up to 3 years

• Time to progression during second-line therapy

  up to 3 years

• Duration of response

  up to 3 years

• Quality of life

  up to 3 years

Study Arms (2)

Arm I (second-line therapy)

ACTIVE COMPARATOR

Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

Biological: bevacizumab; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin

Arm II (second-line therapy)

EXPERIMENTAL

Patients receive bevacizumab and modified FOLFOX7 as in arm I. Patients also receive cetuximab IV over 2 hours on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

Biological: bevacizumab; Biological: cetuximab; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin

Interventions

bevacizumab BIOLOGICAL

Given IV

Arm I (second-line therapy); Arm II (second-line therapy)

cetuximab BIOLOGICAL

Given IV

Arm II (second-line therapy)

fluorouracil DRUG

Given IV

Arm I (second-line therapy); Arm II (second-line therapy)

leucovorin calcium DRUG

Given IV

Arm I (second-line therapy); Arm II (second-line therapy)

oxaliplatin DRUG

Given IV

Arm I (second-line therapy); Arm II (second-line therapy)

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed stage IV colorectal cancer * Measurable disease, defined as at least one lesion whose longest diameter can be accurately measured as ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan * Must not be a candidate for neoadjuvant therapy * No CNS or brain metastases PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy ≥ 12 weeks * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10.0 g/dL * Total bilirubin \< 1.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 3 times ULN * AST ≤ 3 times ULN * Creatinine ≤ 1.5 x times ULN * Proteinuria \< 1+ by urinalysis OR proteinuria \< 1 g by 24-hour urine collection * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * English-speaking patients must have the ability to complete questionnaires by themselves or with assistance * Must be willing to provide blood and tissue samples for research purposes * No history of hypertensive crisis or hypertensive encephalopathy * No blood pressure \> 150/100 mm Hg * No New York Heart Association (NYHA) class II-IV congestive heart failure * No myocardial infarction or unstable angina within the past 6 months * No stroke or transient ischemic attack within the past 6 months * No clinically significant vascular disease (e.g., aortic aneurysm or aortic dissection) * No clinically significant peripheral vascular disease * No evidence of bleeding diathesis or coagulopathy * No significant traumatic injury within the past 28 days * No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months * No serious nonhealing wound, ulcer, or bone fracture PRIOR CONCURRENT THERAPY: * No prior nonsurgical treatment for stage IV disease * Adjuvant therapy allowed if completed \> 6 months prior to study registration * More than 4 weeks since prior and no concurrent or planned participation in another experimental drug study * No prior therapy that specifically and directly targets the EGFR pathway * No prior monoclonal antibody therapy * More than 28 days since prior major surgery or open biopsy * More than 7 days since prior minor surgery, such as fine-needle aspirations or core biopsies * Placement of a vascular access device does not have to meet this criterion * No concurrent major surgery

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

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Cetuximab; Fluorouracil; Leucovorin; 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; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Axel Grothey, MD

  Mayo Clinic

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2007
• First Posted: December 12, 2007
• Last Updated: July 6, 2016

Record last verified: 2016-07