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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer	Drug: Bevacizumab; Drug: Oxaliplatin; Drug: levo-folinic acid; Drug: 5-fluorouracil; Drug: Capecitabine	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	230 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Randomized Phase 3 Study on the Optimization of Bevacizumab With mFOLFOX/mOXXEL in the Treatment of Patients With Metastatic Colorectal Cancer
Study Start Date :	May 2012
Estimated Primary Completion Date :	November 2017
Estimated Study Completion Date :	June 2018

Arms and Interventions

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Arm	Intervention/treatment
Experimental: bevacizumab before chemotherapy; Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)	Drug: Bevacizumab; 5 mg/kg every 2 weeks for up to 24 weeks. After 24 weeks, those patients without disease progression will receive bevacizumab 7.5 mg/kg every 3 weeks until progression of disease or unacceptable toxicity.; Other Name: Avastin Drug: Oxaliplatin; 85mg/m2 IV every 2 weeks for up to 24 weeks Drug: levo-folinic acid; 200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks Drug: 5-fluorouracil; 400 mg/m2 IV bolus followed by 2400 mg/m2 IV infusion over 46 hours, every 2 weeks for up to 24 weeks (given in mFOLFOX-6 schedule) Drug: Capecitabine; 1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule)
Active Comparator: bevacizumab with chemotherapy; Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL)	Drug: Bevacizumab; 5 mg/kg every 2 weeks for up to 24 weeks. After 24 weeks, those patients without disease progression will receive bevacizumab 7.5 mg/kg every 3 weeks until progression of disease or unacceptable toxicity.; Other Name: Avastin Drug: Oxaliplatin; 85mg/m2 IV every 2 weeks for up to 24 weeks Drug: levo-folinic acid; 200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks Drug: 5-fluorouracil; 400 mg/m2 IV bolus followed by 2400 mg/m2 IV infusion over 46 hours, every 2 weeks for up to 24 weeks (given in mFOLFOX-6 schedule) Drug: Capecitabine; 1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule)

Outcome Measures

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Primary Outcome Measures :

1. number of objective responses [ Time Frame: 6 months ]

Secondary Outcome Measures :

1. progression free survival [ Time Frame: one year ]
2. overall survival [ Time Frame: 30 months ]
3. worst grade toxicity per patient [ Time Frame: evaluated every 2 weeks up to 6 months ]
4. changes in quality of life [ Time Frame: measured at baseline, 12 weeks, and 24 weeks ]

Other Outcome Measures:

1. evaluation of prognostic and predictive factors [ Time Frame: 1 year ]
   circulating endothelial cell counts, cytokines, antiangiogenic factors, single nucleotide polymorphisms of VEGF, leukocyte count 24 hours after administration of bevacizumab, and mRNA will be evaluated in blood samples of participating consenting patients, for correlation with clinical outcomes of patients
2. change in metabolic tumor volume [ Time Frame: 11 days from first day of first cycle of chemotherapy ]
   measured by PET scan

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Napoli, Italy

Sponsors and Collaborators

National Cancer Institute, Naples

Investigators

Principal Investigator:	Antonio Avallone, M.D.	National Cancer Institute, Naples

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Avallone A, Piccirillo MC, Aloj L, Nasti G, Delrio P, Izzo F, Di Gennaro E, Tatangelo F, Granata V, Cavalcanti E, Maiolino P, Bianco F, Aprea P, De Bellis M, Pecori B, Rosati G, Carlomagno C, Bertolini A, Gallo C, Romano C, Leone A, Caracò C, de Lutio di Castelguidone E, Daniele G, Catalano O, Botti G, Petrillo A, Romano GM, Iaffaioli VR, Lastoria S, Perrone F, Budillon A. A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme). BMC Cancer. 2016 Feb 8;16:69. doi: 10.1186/s12885-016-2102-y.

Responsible Party:	National Cancer Institute, Naples
ClinicalTrials.gov Identifier:	NCT01718873 History of Changes
Other Study ID Numbers:	OBELICS; 2011-004997-27 ( EudraCT Number )
First Posted:	October 31, 2012
Last Update Posted:	March 29, 2017
Last Verified:	March 2017

Keywords provided by National Cancer Institute, Naples:

metastatic; stage IV

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Bevacizumab; Oxaliplatin; Capecitabine; Fluorouracil	Leucovorin; Folic Acid; Levoleucovorin; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Antidotes