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

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00571740
First received: December 11, 2007
Last updated: November 2, 2009
Last verified: December 2008
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Biological: bevacizumab
Biological: cetuximab
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of Cetuximab/Bevacizumab (CB) as Palliative First-Line Therapy in Patients With Advanced Colorectal Cancer Followed by FOLFOX+CB vs. FOLFOX+B

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival (PFS) rate at 6 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor response rate associated with second-line therapy [ Designated as safety issue: No ]
  • Time to progression during second-line therapy [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Quality of life [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: October 2007
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (second-line therapy)
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
Given IV
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV
Experimental: Arm II (second-line therapy)
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
Given IV
Biological: cetuximab
Given IV
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00571740

Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Axel Grothey, MD Mayo Clinic
Investigator: Val J. Lowe, MD Mayo Clinic
Investigator: Debabrata Mukhopadhyay, PhD Mayo Clinic
  More Information

No publications provided

Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT00571740     History of Changes
Other Study ID Numbers: CDR0000578111, NCCTG-N0548
Study First Received: December 11, 2007
Last Updated: November 2, 2009
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

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

ClinicalTrials.gov processed this record on October 29, 2014