Optimized Chemotherapy Followed by Maintenance With Bevacizumab With or Without Erlotinib in Treating Patients With Metastatic Colorectal Cancer That Cannot be Removed by Surgery (DREAM)

Study Overview
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Brief Summary
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PURPOSE: This randomized phase III trial is studying maintenance therapy with bevacizumab alone after an induction therapy combining bevacizumab+chemotherapy to see how well they work compared to maintenance therapy with bevacizumab+erlotinib alone after an induction therapy combining bevacizumab+chemotherapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Compare Progression-free survival during maintenance period (Maintenance PFS)in patients with unresectable metastatic colorectal cancer. Secondary Compare the duration of disease control and overall survival of patients treated with these regimens. Compare the tolerability of these regimens in these patients. Compare the quality of life of patients treated with these regimens. Compare the occurrence of secondary surgery in patients treated with these regimens. Compare the chemotherapy-free intervals and response rates in patients treated with these regimens. INDUCTION THERAPY Bevacizumab IV over 30-90 minutes on day 1, combined with either: modified FOLFOX7 (IV : oxaliplatin, folinic acid, fluorouracil), XELOX2 (IV : oxaliplatin, oral capecitabine day 1 to 8), FOLFIRI (IV : irinotecan, folinic acid, fluorouracil). Treatment repeats every 2 weeks. RANDOMIZATION Patients with stable or responding disease then receive maintenance therapy with bevacizumab alone or bevacizumab+erlotinib MAINTENANCE THERAPY Arm A : bevacizumab alone : bevacizumab IV over 30-90 minutes on day 1 Arm B : bevacizumab+erlotinib : bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib once daily on days 1-21. In both arms, treatment with bevacizumab +/- erlotinib repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. ACCRUAL: A total of 700 patients will be accrued for this study.

Official Title
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Phase III Study of an Optimized Chemotherapy Followed by Maintenance With Bevacizumab Strategy With or Without Erlotinib in Unresectable Metastatic Colorectal Cancer. DREAM OPTIMOX 3. C04-2

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: bevacizumab
* Drug: bevacizumab, erlotinib


Participation Criteria
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Eligibility Criteria
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MAIN ELIGIBILITY CRITERIA Histologically proven metastatic adenocarcinoma of colon or rectum Documented inoperable disease (i.e., not suitable for complete carcinological surgical resection) Measurable lesion as assessed by CT scan or MRI in at least one dimension (longest diameter to be recorded) ≥ 20 mm with conventional CT scan or ≥ 10 mm with spiral CT scan No previous therapy for metastatic disease No history or evidence upon physical examination of CNS disease (e.g., non-irradiated CNS metastasis, seizure not controlled with standard medical therapy, or history of stroke) unless adequately treated No exclusive bone metastasis ECOG performance status 0-2 WBC ≥ 1,500/mm^3 Platelets ≥ 100,000/mm^3 Hemoglobin > 9 g/dL (may be transfused to maintain or exceed this level) Proteinuria < 2+ by dipstick OR ≤ 1 g of protein on 24-hr urine collection Bilirubin < 1.5 times ULN Alkaline phosphatase < 3 times ULN No peripheral sensory neuropathy Negative pregnancy test Fertile patients must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterilization) No peripheral neuropathy ≥ grade 1 No clinically significant (i.e. active) cardiovascular disease No evidence of bleeding diathesis or coagulopathy No serious, non-healing wound, ulcer, or bone fracture No significant ophthalmologic abnormality More than 28 days since prior major surgical procedure or open biopsy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: bevacizumab alone<br> | Drug: bevacizumab<br>* bevacizumab 7.5mg/kg every 3 weeks until disease progression or limiting toxicity<br>|
| Experimental: Bevacizumab + erlotinib<br> | Drug: bevacizumab, erlotinib<br>* bevacizumab 7.5mg/kg and oral erlotinib 150 mg/day continuously Cycles every 3 weeks until disease progression or limiting toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival during maintenance therapy |  | Tumor evaluation every 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV colon cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum, chemotherapy