Optimization of Bevacizumab Scheduling With Chemotherapy for Metastatic Colorectal Cancer - Full Text View

Purpose

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	Intervention	Phase
Colorectal Cancer	Drug: Bevacizumab Drug: Oxaliplatin Drug: levo-folinic acid Drug: 5-fluorouracil Drug: Capecitabine	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Fluorouracil Folic acid Oxaliplatin Capecitabine Bevacizumab

U.S. FDA Resources

Further study details as provided by National Cancer Institute, Naples:

Primary Outcome Measures:

number of objective responses [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

progression free survival [ Time Frame: one year ] [ Designated as safety issue: No ]
overall survival [ Time Frame: 30 months ] [ Designated as safety issue: No ]
worst grade toxicity per patient [ Time Frame: evaluated every 2 weeks up to 6 months ] [ Designated as safety issue: Yes ]
changes in quality of life [ Time Frame: measured at baseline, 12 weeks, and 24 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:

evaluation of prognostic and predictive factors [ Time Frame: 1 year ] [ Designated as safety issue: No ]
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
change in metabolic tumor volume [ Time Frame: 11 days from first day of first cycle of chemotherapy ] [ Designated as safety issue: No ]
measured by PET scan


Estimated Enrollment:	230
Study Start Date:	May 2012
Estimated Study Completion Date:	June 2017
Estimated Primary Completion Date:	June 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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)

Arms

Assigned Interventions

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)

Eligibility


Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01718873

Contacts


Contact: Antonio Avallone, M.D.	+39 081 5903629	avalloneantonio@libero.it

Locations


Italy
Istituto Nazionale Tumori Fondazione G. Pascale	Recruiting
Napoli, Italy

Sponsors and Collaborators

National Cancer Institute, Naples

Investigators


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

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
Study First Received:	October 29, 2012
Last Updated:	November 27, 2015
Health Authority:	Italy: Ethics Committee

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

ClinicalTrials.gov processed this record on September 28, 2016

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