Optimization of Bevacizumab Scheduling With Chemotherapy for Metastatic Colorectal Cancer (OBELICS)

National Cancer Institute, Naples

Status and phase: Completed; Phase 3

Conditions: Colorectal Cancer

Treatments: Drug: levo-folinic acid; Drug: Oxaliplatin; Drug: 5-fluorouracil; Drug: Bevacizumab; Drug: Capecitabine

Study type: Interventional

Funder types: Other

Identifiers

NCT01718873

2011-004997-27 (EudraCT Number)

OBELICS

Details and patient eligibility

About

The purpose of this study is to evaluate if giving bevacizumab prior to chemotherapy compared to giving bevacizumab at the same time as chemotherapy improves patient overall response to treatment.

Full description

OBELICS is a two-arm phase 3 trial comparing in mCRC patients (1:1): concurrent administration of bevacizumab in combination with modified FOLFOX-6 regimen (mFOLFOX-6) or modified OXXEL regimen (mOXXEL), in which bevacizumab is administered the same day as oxaliplatin, (standard arm); and sequential administration of bevacizumab with the same chemotherapeutic regimens, in which bevacizumab is administered 4 days before oxaliplatin at each cycle (experimental arm) Oxaliplatin regimen (mFOLFOX/mOXXEL) is chosen according to local clinical practice at the beginning of the study.

Enrollment: 230 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histological diagnosis of colorectal adenoma carcinoma
• Stage IV disease
• Presence of at least one measurable target lesion (according to RECIST), and not previously radiated.
• Age ≥ 18 e ≤ 75 years
• ECOG Performance status 0-1
• Life expectancy >3 months
• Adequate recovery from surgery, with at least 28 days from surgery to date of pre-study biopsy.
• Adequate contraception for male and female patients of child bearing potential
• informed consent

Exclusion criteria

• More than one previous line of therapy for metastatic disease
• Prior treatment with bevacizumab or oxaliplatin (previous treatment with irinotecan,, cetuximab, fluoropyrimidine, folic acid are permitted)
• Primary tumor that is stenosing and/or that infiltrates the entire thickness of the intestinal wall
• Regular use of NSAIDs or aspirin
• Bleeding disorders or coagulopathy
• Concurrent anticoagulant therapy
• Suspected or cerebral metastases (to verify in the presence of symptoms)
• Neutrophils < 2000 / mm3, platelets < 100,000 / mm3, hemoglobin < 9g/dl
• Creatinine > 1.5 times the upper normal limit
• GOT and/or GPT > 2.5 times the upper normal limit, bilirubin > 1.5 times the upper normal limit in absence of liver metastases
• GOT and/or GPT > 5 times the upper normal limit, bilirubin > 3 times the upper normal limit in presence of liver metastases
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal and squamous cell carcinoma or cervical cancer in situ
• Congestive heart failure, ischemic coronary events within past 12 months, uncontrolled cardiac arrhythmia
• Uncontrolled hypertension
• Active or uncontrolled infection
• Any concomitant condition that, in the investigator's opinion, would contraindicate the use of any of the study drugs
• Pregnancy or lactation
• Central nervous system disorders or peripheral neuropathy > grade 1 (CTCAE v. 4.0)
• Inability to comply with follow up procedures of the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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230 participants in 2 patient groups

bevacizumab before chemotherapy

Experimental group

Description:

Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)

Treatment:

Drug: Capecitabine

Drug: Bevacizumab

Drug: 5-fluorouracil

Drug: Oxaliplatin

Drug: levo-folinic acid

bevacizumab with chemotherapy

Active Comparator group

Description:

Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)

Treatment:

Drug: Capecitabine

Drug: Bevacizumab

Drug: 5-fluorouracil

Drug: Oxaliplatin

Drug: levo-folinic acid