Optimization of Bevacizumab Scheduling With Chemotherapy for Metastatic Colorectal Cancer

NCT ID: NCT01718873

Last Updated: 2023-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2019-12-31

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.

Detailed 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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

bevacizumab before chemotherapy

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

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

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.

Oxaliplatin

Intervention Type: DRUG

85mg/m2 IV every 2 weeks for up to 24 weeks

levo-folinic acid

Intervention Type: DRUG

200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks

5-fluorouracil

Intervention Type: DRUG

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)

Capecitabine

Intervention Type: DRUG

1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule)

bevacizumab with chemotherapy

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

Group Type: ACTIVE_COMPARATOR

Bevacizumab

Intervention Type: DRUG

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.

Oxaliplatin

Intervention Type: DRUG

85mg/m2 IV every 2 weeks for up to 24 weeks

levo-folinic acid

Intervention Type: DRUG

200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks

5-fluorouracil

Intervention Type: DRUG

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)

Capecitabine

Intervention Type: DRUG

1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule)

Interventions

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.

Intervention Type: DRUG

Oxaliplatin

85mg/m2 IV every 2 weeks for up to 24 weeks

Intervention Type: DRUG

levo-folinic acid

200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks

Intervention Type: 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)

Intervention Type: DRUG

Capecitabine

1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule)

Intervention Type: DRUG

Other Intervention Names

Avastin; Eloxatin; Lederfolin; Fluorouracil; Xeloda

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute, Naples

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Avallone, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute, Naples

Locations

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, , Italy

Countries

Italy

References

Avallone A, Piccirillo MC, Nasti G, Rosati G, Carlomagno C, Di Gennaro E, Romano C, Tatangelo F, Granata V, Cassata A, Silvestro L, De Stefano A, Aloj L, Vicario V, Nappi A, Leone A, Bilancia D, Arenare L, Petrillo A, Lastoria S, Gallo C, Botti G, Delrio P, Izzo F, Perrone F, Budillon A. Effect of Bevacizumab in Combination With Standard Oxaliplatin-Based Regimens in Patients With Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2021 Jul 1;4(7):e2118475. doi: 10.1001/jamanetworkopen.2021.18475.

Reference Type: DERIVED

PMID: 34309665 (View on PubMed)

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, Caraco 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.

Reference Type: DERIVED

PMID: 26857924 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2011-004997-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

OBELICS

Identifier Type: -

Identifier Source: org_study_id