Maintenance and Reinduction Chemotherapy With Avastin in Metastatic Colon Cancer: The MARTHA (SICOG 0803) Trial
18 Years
75 Years
Both
Colorectal Cancer
Trial Information
Maintenance and Reinduction Chemotherapy With Avastin in Metastatic Colon Cancer: The MARTHA (SICOG 0803) Trial
OBJECTIVES:
Primary
- To compare two strategies of induction bio-chemotherapy followed by the same
maintenance biotherapy in terms of time to failure in patients with previously
untreated metastatic colorectal cancer.
Secondary
- To compare the two arms of treatment in terms of response rate, duration of responses,
progression-free survival, safety, and quality of life of these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to treatment center,
performance status (0 vs 1), and number of metastatic sites (1 vs ≥ 2). Patients are
randomized to 1 of 2 induction therapy arms.
- Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also
receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 1 hour and
leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46
hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses in the
absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive bevacizumab and FOLFIRI chemotherapy (B-FOLFIRI) as in arm I.
Treatment repeats every 2 weeks for up to 6 courses in the absence of disease
progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90
minutes on day 1 and oral capecitabine once every 12 hours on days 1-14. Treatment
repeats every 3 weeks for up to 4 courses in the absence of disease progression or
unacceptable toxicity.
In both arms, patients achieving stable disease after completion of 6 months of induction
therapy proceed to maintenance therapy.
- Maintenance therapy: Patients receive bevacizumab IV over 30-90 minutes every 3 weeks
for up to 1 year in the absence of disease progression or unacceptable toxicity.
During or after completion of maintenance therapy, patients with tumor regrowth that is not
classified as disease progression from baseline and who achieved partial or complete
response during or after their induction therapy proceed to reinduction therapy.
- Reinduction therapy: Patients receive B-FOLFIRI as described previously. Quality of
life is assessed at baseline, every 3 months during induction therapy, and at
discontinuation of study therapy.
After completion of study therapy, patients are followed for up to 2 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed colorectal cancer
- Metastatic disease that is not amenable to surgery
- At least one measurable lesion according to RECIST criteria
- No untreated brain metastases or spinal cord compression
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Life expectancy ≥ 12 weeks
- Hemoglobin ≥ 9.0 g/dL
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and/or ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
- Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
- PT-INR/PTT < 1.5 times ULN
- Creatinine clearance > 50 mL/min OR serum creatinine ≤ 1.5 times ULN
- Proteinuria on dipstick urinalysis < 2+ OR 24-hour urine protein ≤ 1g
- Not pregnant or nursing
- Negative pregnancy test
- Must be accessible for treatment and follow-up
- No history of inflammatory bowel disease and/or acute or subacute bowel occlusion
- No serious non-healing wound, ulcer, or bone fracture
- No evidence of bleeding diathesis or coagulopathy
- No uncontrolled hypertension
- No clinically significant cardiovascular disease including any of the following:
- Cerebrovascular accident within the past 6 months
- Myocardial infarction within the past 6 months
- Unstable angina
- New York Heart Association grade II-IV congestive heart failure
- Serious cardiac arrhythmia requiring medication
- No known allergy to Chinese hamster ovary cell proteins or any of the components of
the study medications
- No other malignancy within the past 5 years except basal cell and squamous cell skin
cancer or carcinoma in situ of the cervix
- No significant traumatic injury within the past 28 days
- No substance abuse or medical, psychological, or social conditions that may interfere
with participation in the study or the evaluation of study results
- Able to swallow oral medications
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 6 months since prior adjuvant treatment
- No prior irinotecan and/or bevacizumab during prior adjuvant therapy
- No prior cytotoxic drugs for the metastatic disease
- More than 10 days since prior and no concurrent anticoagulants for therapeutic
purposes
- No chronic, daily treatment with high-dose aspirin (> 325 mg/day) or other
medications known to predispose to gastrointestinal ulceration
- No treatment with any investigational drug within the past 30 days
- No major surgical procedure or open biopsy within the past 28 days or anticipated
need for a major surgical procedure during the course of the study
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Time to failure of strategy
Safety Issue:
No
Principal Investigator
Pasquale Comella, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Istituto Nazionale per lo Studio e la Cura dei Tumori
Authority:
Unspecified
Study ID:
CDR0000617983
NCT ID:
NCT00797485
Start Date:
July 2008
Completion Date:
Related Keywords:
- Colorectal Cancer
- stage IV colon cancer
- stage IV rectal cancer
- Colonic Neoplasms
- Colorectal Neoplasms
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