Clinical trial NCT01718873: Optimization of Bevacizumab Scheduling With Chemotherapy for Metastatic Colorectal Cancer
Official title: Randomized Phase 3 Study on the Optimization of Bevacizumab With mFOLFOX/mOXXEL in the Treatment of Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: metastatic
stage IV
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2012-10-31
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate
timeFrame: Objective response was assessed by computed tomographic scan or other appropriate imaging at weeks 12 and 24 from randomization, and every 3 months thereafter, assessed up to 90 months.
Secondary outcomes:
measure: Disease Control Rate
timeFrame: At weeks 12 and 24 from randomization and every 3 months thereafter, assessed up to 90 months
measure: Overall Survival
timeFrame: assessed up to 90 months
measure: Progression-free Survival (PFS)
timeFrame: assessed up to 90 months
measure: Toxic Effects
timeFrame: up to 4 weeks after the end of the treatment
Other outcomes:
Locations:
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
Study officials:
affiliation: National Cancer Institute, Naples
name: Antonio Avallone, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.