Clinical trial NCT00265824: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
chemotherapy
Lead sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
Sponsor class: OTHER
First posted: 2005-12-15
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-free survival during maintenance therapy
timeFrame: Tumor evaluation every 2 months
Secondary outcomes:
Other outcomes:
Locations:
city: Leoben
country: Austria
facility: LKH Leoben
city: Steyr
country: Austria
facility: LKH Steyr
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Wien
country: Austria
facility: AKH Universitätsklinik für Innere Medizin I
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre
state: Ontario
city: Laval
country: Canada
facility: Cité de la Santé de Laval
state: Quebec
city: Montreal
country: Canada
facility: CHUM Hôpital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: Mc Gill University Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hôpital Charles LeMoyne
state: Quebec
city: Montréal
country: Canada
facility: Hôpital Maisonneuve-Rosemont
state: Quebec
city: Antibes
country: France
facility: Centre Hospitalier
city: Auxerre
country: France
facility: Centre Hospitalier
city: Beauvais
country: France
facility: Centre Hospitalier
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord
city: Briey
country: France
facility: Centre Hospitalier
city: Colmar
country: France
facility: Hôpital Pasteur
city: Dax
country: France
facility: Centre Hospitalier
city: Dijon
country: France
facility: Hopital Drevon
city: La Roche sur Yon
country: France
facility: CHD les oudairies
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Libourne
country: France
facility: Hopital Robert Boulin
city: Limoges
country: France
facility: CHU Dupuytren
city: Lyon
country: France
facility: Centre Hospitalier Saint Joseph Saint Luc
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Lyon
country: France
facility: Clinique de la sauvegarde
city: Marseille
country: France
facility: hôpital Ambroise Paré
city: Marseille
country: France
facility: Institu Paoli Calmette
city: Meaux
country: France
facility: Centre Hospitalier
city: Metz
country: France
facility: Clinique Claude BERNARD
city: Mont de Marsan
country: France
facility: Centre hospitalier Layné
city: Montfermeil
country: France
facility: Centre Hospitalier Intercommunal Le Raincy - Montfermeil
city: Nancy
country: France
facility: centre oncologie de Gentilly
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Groupe Hospitalier les Diaconnesses
city: Paris
country: France
facility: Hôpital Pitié Salpêtrière
city: Paris
country: France
facility: Hôpital Saint Joseph
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: Hopital Tenon
city: Perpignan
country: France
facility: centre Catalan oncologie
city: Saint Brieuc
country: France
facility: Clinique Armoricaine
city: Semur en Auxois
country: France
facility: Centre Hospitalier
city: Senlis
country: France
facility: C.H. Senlis
city: Suresnes
country: France
facility: Hopital Foch
city: Valence
country: France
facility: Clinique Générale
Study officials:
affiliation: Hopital Saint Antoine
name: Aimery de Gramont, MD
role: STUDY_CHAIR
affiliation: Hopital Henri Mondor
name: Christophe Tournigand, MD
role: STUDY_CHAIR
References:
citation: 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.