Optimization of Bevacizumab Scheduling With Chemotherapy for Metastatic Colorectal Cancer

NCT01718873 | Completed Phase 3 Results

• 2 other identifiers: OBELICS2011-004997-27
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer

Keywords

metastatic; stage IV

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective response rate (ORR), according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, was the primary end point and was defined as the number of complete plus partial responses divided by the number of enrolled patients. Per RECIST v 1.1 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  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 (4)

• Disease Control Rate

  At weeks 12 and 24 from randomization and every 3 months thereafter, assessed up to 90 months

• Overall Survival

  assessed up to 90 months

• Progression-free Survival (PFS)

  assessed up to 90 months

• Toxic Effects

  up to 4 weeks after the end of the treatment

Study Arms (2)

bevacizumab before chemotherapy

EXPERIMENTAL

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

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

bevacizumab with chemotherapy

ACTIVE COMPARATOR

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

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

Interventions

Bevacizumab 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.

Also known as: Avastin

bevacizumab before chemotherapy; bevacizumab with chemotherapy

Oxaliplatin DRUG

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

Also known as: Eloxatin

bevacizumab before chemotherapy; bevacizumab with chemotherapy

levo-folinic acid DRUG

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

Also known as: Lederfolin

bevacizumab before chemotherapy; bevacizumab with chemotherapy

5-fluorouracil 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)

Also known as: Fluorouracil

bevacizumab before chemotherapy; bevacizumab with chemotherapy

Capecitabine DRUG

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

Also known as: Xeloda

bevacizumab before chemotherapy; bevacizumab with chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (1)

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, Italy

Location

Related Publications (2)

• 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.

  PMID: 34309665 DERIVED

• 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.

  PMID: 26857924 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

Bevacizumab; Oxaliplatin; Leucovorin; Fluorouracil; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Considering that the accuracy of conventional evaluation of tumor response by RECIST criteria to bevacizumab combination treatment has been questioned, we acknowledge that our choice of ORR as primary end point may have been inadequate. We are also aware that balancing out unmeasurable differences in patient outcome through randomization is not always achieved with confidence in trials with a relatively small sample size.

Results Point of Contact

• Title: Antonio Avallone, Dierctor of Experimental Abdominal Medcial Oncology
• Organization: National Cancer Institute, IRCCS, G. Pascale Foundation

a.avallone@istitutotumori.na.it

+390815903629

Study Officials

• Antonio Avallone, M.D.

  National Cancer Institute, Naples

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2012
• First Posted: October 31, 2012
• Study Start: May 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2019
• Last Updated: April 12, 2023
• Results First Posted: April 12, 2023

Record last verified: 2021-10

Locations

IT (1)