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)

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: bevacizumab; Drug: bevacizumab, erlotinib

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
• Enrollment (Actual): 700
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Leoben, Austria, 8700
    • LKH Leoben
  • Steyr, Austria, 4400
    • LKH Steyr
  • Wels, Austria, 4600
    • Klinikum Wels-Grieskirchen GmbH
  • Wien, Austria, 1090
    • AKH Universitätsklinik für Innere Medizin I
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, H7M 3L9
      • Ottawa Hospital Regional Cancer Centre
  • Quebec
    • Laval, Quebec, Canada, H7M 3L9
      • Cité de la santé de Laval
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM Hopital Notre-Dame
    • Montreal, Quebec, Canada, J4V 2H1
      • Hopital Charles LeMoyne
    • Montreal, Quebec, Canada, H2W 1S6
      • Mc Gill University Hospital
    • Montréal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneuve-Rosemont
• France
  • Antibes, France, 06606
    • Centre Hospitalier
  • Auxerre, France, 89011
    • Centre Hospitalier
  • Beauvais, France, 60000
    • Centre Hospitalier
  • Bobigny, France, 93000
    • Hôpital Avicenne
  • Bordeaux, France, 33000
    • Polyclinique Bordeaux Nord
  • Briey, France, 54140
    • Centre Hospitalier
  • Colmar, France, 68024
    • Hôpital Pasteur
  • Dax, France, 40100
    • Centre Hospitalier
  • Dijon, France, 21000
    • Hopital Drevon
  • La Roche sur Yon, France, 85000
    • CHD Les Oudairies
  • Le Mans, France, F-72000
    • Clinique Victor Hugo
  • Libourne, France, 33500
    • Hôpital Robert Boulin
  • Limoges, France, 87000
    • Chu Dupuytren
  • Lyon, France, 69008
    • Hopital Prive Jean Mermoz
  • Lyon, France, 69009
    • Clinique de la Sauvegarde
  • Lyon, France, 69007
    • Centre Hospitalier Saint Joseph Saint Luc
  • Marseille, France, 13000
    • Hopital Ambroise Pare
  • Marseille, France, 13000
    • Institu Paoli Calmette
  • Meaux, France, 77100
    • Centre Hospitalier
  • Metz, France, 57070
    • Clinique Claude Bernard
  • Mont de Marsan, France, 40000
    • Centre Hospitalier Layné
  • Montfermeil, France, 93370
    • Centre Hospitalier Intercommunal Le Raincy - Montfermeil
  • Nancy, France, 54100
    • centre oncologie de Gentilly
  • Nantes, France, 44000
    • Centre Catherine de Sienne
  • Paris, France, 75970
    • Hopital Tenon
  • Paris, France, 75014
    • Hopital Saint Joseph
  • Paris, France, 75014
    • Institut Mutualiste Montsouris
  • Paris, France, 75571
    • Hopital Saint Antoine
  • Paris, France, 75005
    • Institut Curie
  • Paris, France, 75013
    • Hopital Pitie Salpetriere
  • Paris, France, 75012
    • Groupe Hospitalier les Diaconnesses
  • Perpignan, France, 66000
    • centre Catalan oncologie
  • Saint Brieuc, France, 22000
    • Clinique Armoricaine
  • Semur en Auxois, France, 21140
    • Centre Hospitalier
  • Senlis, France, 60309
    • C.H. Senlis
  • Suresnes, France, 92151
    • Hôpital FOCH
  • Valence, France, 26000
    • Clinique Générale

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Investigators: Study Chair: Aimery de Gramont, MD, Hopital Saint Antoine; Study Chair: Christophe Tournigand, MD, Hôpital Henri Mondor

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: December 14, 2005
• First Submitted That Met QC Criteria: December 14, 2005
• First Posted (Estimate): December 15, 2005

Study Record Updates

• Last Update Posted (Estimate): December 11, 2015
• Last Update Submitted That Met QC Criteria: December 10, 2015
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: chemotherapy; adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Erlotinib Hydrochloride; Bevacizumab
• Other Study ID Numbers: CDR0000453861; GERCOR-C04-2; EU-20565; GERCOR-OPTIMOX3; GERCOR-DREAM- C04-2