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
18 Years
N/A
Both
Colorectal Cancer
Trial Information
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
OBJECTIVES:
Primary
- To assess the efficacy of bevacizumab and cetuximab as first-line treatment for
metastatic colorectal cancer, as measured by percentage of patients who remain
progression-free at 6 months.
Secondary
- To evaluate adverse events, confirmed response, duration of response, time to disease
progression, time to treatment failure, and survival of patients treated with
bevacizumab and cetuximab.
- To evaluate adverse events, confirmed response, duration of response, time to disease
progression, time to treatment failure, and survival of patients who are refractory to
dual-agent bevacizumab and cetuximab and are subsequently treated with modified FOLFOX7
chemotherapy and bevacizumab with or without cetuximab.
- To evaluate quality of life parameters in patients treated with these regimens.
- To estimate the direct medical resource utilization and costs.
- To assess the reliability of FDG-PET as a measurement of early treatment response, as
measured by percentage of patients who are progression-free at 6 months.
- To identify circulating angiogenesis biomarkers.
- To assay the activity of pro-angiogenic factors in plasma angiogenic assays.
OUTLINE: This is a multicenter study*. Patients are stratified according to ECOG performance
status (0-1 vs 2) and number of metastatic sites (1 vs > 1).
NOTE: *Participating site must be PET-qualified.
- First-line therapy: Patients receive bevacizumab IV over 30-90 minutes and cetuximab IV
over 2 hours on day 1. Treatment repeats every 2 weeks in the absence of disease
progression or unacceptable toxicity. Patients with progressive disease proceed to
second-line therapy.
- Second-line therapy: Patients are randomized* to 1 of 2 treatment arms.
- Arm I (modified FOLFOX7 with bevacizumab only): 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.
- Arm II (modified FOLFOX7 with bevacizumab and cetuximab): 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.
NOTE: *Randomization occurs prior to receiving first-line therapy.
Patients undergo blood sample collection periodically for translational studies. Samples are
analyzed for circulating endothelial cells and endothelial progenitor cells via flow
cytometry; angiogenic activity of serum/plasma in angiogenesis-dependent diseases via
endothelial proliferation assay and matrigel tube formation assay; and circulating
angiogenesis biomarkers (i.e., free VEGF, soluble FLT-1, and KDR) via ELISA.
Quality of life is assessed periodically using the UNISCALE, Skindex-16, and Skin Assessment
Questionnaires.
After completion of study treatment, patients are followed every 6 months for up to 3 years.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Outcome Measure:
Progression-free survival (PFS) rate at 6 months
Safety Issue:
No
Principal Investigator
Axel Grothey, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
Unspecified
Study ID:
CDR0000578111
NCT ID:
NCT00571740
Start Date:
October 2007
Completion Date:
Related Keywords:
- Colorectal Cancer
- stage IV colon cancer
- stage IV rectal cancer
- recurrent colon cancer
- recurrent rectal cancer
- Colorectal Neoplasms
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