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) (DREAM)

• ClinicalTrials.gov Identifier: NCT00265824
• Recruitment Status: Completed
• First Posted: December 15, 2005
• Last Update Posted: December 11, 2015
• Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Information provided by (Responsible Party): GERCOR - Multidisciplinary Oncology Cooperative Group

Tracking Information

• First Submitted Date: December 14, 2005
• First Posted Date: December 15, 2005
• Last Update Posted Date: December 11, 2015
• Study Start Date: May 2005
• Actual Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 21, 2012): Progression-free survival during maintenance therapy [ Time Frame: Tumor evaluation every 2 months ]
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official Title: 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
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer

Intervention

• Drug: bevacizumab
  bevacizumab 7.5mg/kg every 3 weeks until disease progression or limiting toxicity
• Drug: bevacizumab, erlotinib
  bevacizumab 7.5mg/kg and oral erlotinib 150 mg/day continuously Cycles every 3 weeks until disease progression or limiting toxicity

Study Arms

• Active Comparator: bevacizumab alone
  Intervention: Drug: bevacizumab
• Experimental: Bevacizumab + erlotinib
  Intervention: Drug: bevacizumab, erlotinib

• Publications *: Tournigand C, Chibaudel B, Samson B, Scheithauer W, Vernerey D, Mesange P, Lledo G, Viret F, Ramee JF, Tubiana-Mathieu N, Dauba J, Dupuis O, Rinaldi Y, Mabro M, Aucoin N, Latreille J, Bonnetain F, Louvet C, Larsen AK, Andre T, de Gramont A. Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1493-1505. doi: 10.1016/S1470-2045(15)00216-8. Epub 2015 Oct 22. Erratum In: Lancet Oncol. 2015 Dec;16(16):e589.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 21, 2012): 700
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Actual Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Canada, France

Administrative Information

• NCT Number: NCT00265824
• Other Study ID Numbers: CDR0000453861; GERCOR-C04-2; EU-20565; GERCOR-OPTIMOX3; GERCOR-DREAM- C04-2
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: GERCOR - Multidisciplinary Oncology Cooperative Group
• Original Responsible Party: Not Provided
• Current Study Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Aimery de Gramont, MD; Hopital Saint Antoine
• Study Chair: Christophe Tournigand, MD; Hopital Henri Mondor

• PRS Account: GERCOR - Multidisciplinary Oncology Cooperative Group
• Verification Date: March 2014