A Study Comparing the Efficacy and Safety of Vanucizumab and FOLFOX With Bevacizumab and FOLFOX in Participants With Untreated Metastatic Colorectal Cancer

NCT02141295 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: BP292622013-005108-32
• Study Type: interventional
• Target: 197
• Locations: 6 countries
• Sites: 37

Brief Summary

This is a Phase 2 multicenter, randomized, parallel arms, double-blind study of vanucizumab to evaluate the efficacy and safety of vanucizumab in combination with oxaliplatin, folinic acid, and 5-fluorouracil (5-FU) (mFOLFOX-6) versus bevacizumab (Avastin) + mFOLFOX-6 in participants with previously untreated metastatic colorectal cancer (mCRC). The study consists of 2 parts: a safety run-in open-label, single-arm part (Part 1) and a randomized, parallel-arms, double-blind part (Part 2). During Part 1 at least 6 eligible participants will receive 2000 milligrams (mg) vanucizumab every 2 weeks + mFOLFOX-6 in order to confirm the dose and schedule that will be used in Part 2. In Part 2, all eligible participants will be randomized in a ratio of 1:1 to receive either mFOLFOX-6 + vanucizumab or mFOLFOX-6 + bevacizumab. Study treatment (induction and maintenance) will be given on Day 1 of each 14-day cycle. Induction therapy will consist of up to 8 cycles of mFOLFOX-6 plus either bevacizumab or vanucizumab. Maintenance therapy will consist of 5-fluorouracil and folinic acid plus either vanucizumab or bevacizumab for up to 24 months or until disease progression, unacceptable toxicity, Investigator decision or consent withdrawal, whichever occurs first.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS), Time to Event

  Efficacy of vanucizumab was evaluated in terms of PFS as Investigator-Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). PFS was defined as the time between randomization and the date of first documented disease progression or death from any cause on study, whichever occurred first. Death on study was defined as death from any cause within 30 days of the last study treatment.

  Baseline, every 8 weeks, up to approximately 29 months

Secondary Outcomes (13)

• Percentage of Participants With Objective Response (ORR) as Assessed Using RECIST v. 1.1

  Baseline (within 28 days prior to Day 1), then every 8 weeks until progressive disease (PD), start of other anticancer therapy, withdrawal of consent, or death (up to approximately 29 months)

• Duration of Objective Response, as Assessed Using RECIST v. 1.1

  Baseline (within 28 days prior to Day 1), then every 8 weeks until PD, start of other anticancer therapy, withdrawal of consent, or death (up to approximately 29 months)

• Overall Survival (OS)

  Baseline until death from any cause (maximum up to approximately 3.5 years)

• Percentage of Participants With Adverse Events (AEs)

  Up to approximately 29 months

• Number of Participants With Human Anti-human Antibodies (HAHAs) Against Vanucizumab

  End of study (EoS, within 28 to 42 days after last dose, latest at 29 months)

Study Arms (6)

Part 1 (Induction): Vanucizumab + mFOLFOX-6

EXPERIMENTAL

Participants will receive vanucizumab at a dose of 2000 milligram (mg) as intravenous (IV) infusion; oxaliplatin at a dose of 85 mg per meter-squared (mg/m\^2) as IV infusion; folinic acid at a dose of 400 mg/m\^2 as IV infusion; and 5-FU at a dose of 400 mg/m\^2 as starting IV bolus followed by 2400 mg/m\^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months).

Drug: 5-FU; Drug: Folinic acid; Drug: Oxaliplatin; Drug: Vanucizumab

Part 1 (Maintenance): Vanucizumab + 5-FU + Folinic acid

EXPERIMENTAL

Participants will receive vanucizumab at a dose confirmed during induction as IV infusion; folinic acid at a dose of 400 mg/m\^2 as IV infusion; and 5-FU at a dose of 400 mg/m\^2 as starting IV bolus followed by 2400 mg/m\^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Drug: 5-FU; Drug: Folinic acid; Drug: Vanucizumab

Part 2 (Induction): Bevacizumab + mFOLFOX-6

ACTIVE COMPARATOR

Participants will receive bevacizumab at a dose of 5 milligram per kilogram (mg/kg) as IV infusion; oxaliplatin at a dose of 85 mg/m\^2 as IV infusion; folinic acid at a dose of 400 mg/m\^2 as IV infusion; and 5-FU at a dose of 400 mg/m\^2 as starting IV bolus followed by 2400 mg/m\^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months).

Drug: 5-FU; Drug: Bevacizumab; Drug: Folinic acid; Drug: Oxaliplatin

Part 2 (Induction): Vanucizumab + mFOLFOX-6

EXPERIMENTAL

Participants will receive vanucizumab at a dose confirmed during part 1 as IV infusion; oxaliplatin at a dose of 85 mg/m\^2 as IV infusion; folinic acid at a dose of 400 mg/m\^2 as IV infusion; and 5-FU at a dose of 400 mg/m\^2 as starting IV bolus followed by 2400 mg/m\^2 as IV infusion every 2 weeks for up to 8 cycles (approximately 4 months).

Drug: 5-FU; Drug: Folinic acid; Drug: Oxaliplatin; Drug: Vanucizumab

Part 2 (Maintenance): Bevacizumab + 5-FU + Folinic acid

ACTIVE COMPARATOR

Participants will receive bevacizumab at a dose of 5 mg/kg as IV infusion; folinic acid at a dose of 400 mg/m\^2 as IV infusion; and 5-FU at a dose of 400 mg/m\^2 as starting IV bolus followed by 2400 mg/m\^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Drug: 5-FU; Drug: Bevacizumab; Drug: Folinic acid

Part 2 (Maintenance): Vanucizumab + 5-FU + Folinic acid

EXPERIMENTAL

Participants will receive vanucizumab at a dose confirmed during part 1 as IV infusion; folinic acid at a dose of 400 mg/m\^2 as IV infusion; and 5-FU at a dose of 400 mg/m\^2 as starting IV bolus followed by 2400 mg/m\^2 as IV infusion every 2 weeks until disease progression, unacceptable toxicities, consent withdrawal or Investigator's decision for a maximum of 24 months.

Drug: 5-FU; Drug: Folinic acid; Drug: Vanucizumab

Interventions

5-FU DRUG

5-FU will be administered according to dose and schedule described in respective arm.

Part 1 (Induction): Vanucizumab + mFOLFOX-6; Part 1 (Maintenance): Vanucizumab + 5-FU + Folinic acid; Part 2 (Induction): Bevacizumab + mFOLFOX-6; Part 2 (Induction): Vanucizumab + mFOLFOX-6; Part 2 (Maintenance): Bevacizumab + 5-FU + Folinic acid; Part 2 (Maintenance): Vanucizumab + 5-FU + Folinic acid

Bevacizumab DRUG

Bevacizumab will be administered according to dose and schedule described in respective arm.

Also known as: Avastin

Part 2 (Induction): Bevacizumab + mFOLFOX-6; Part 2 (Maintenance): Bevacizumab + 5-FU + Folinic acid

Folinic acid DRUG

Folinic acid will be administered according to dose and schedule described in respective arm.

Part 1 (Induction): Vanucizumab + mFOLFOX-6; Part 1 (Maintenance): Vanucizumab + 5-FU + Folinic acid; Part 2 (Induction): Bevacizumab + mFOLFOX-6; Part 2 (Induction): Vanucizumab + mFOLFOX-6; Part 2 (Maintenance): Bevacizumab + 5-FU + Folinic acid; Part 2 (Maintenance): Vanucizumab + 5-FU + Folinic acid

Oxaliplatin DRUG

Oxaliplatin will be administered according to dose and schedule described in respective arm.

Part 1 (Induction): Vanucizumab + mFOLFOX-6; Part 2 (Induction): Bevacizumab + mFOLFOX-6; Part 2 (Induction): Vanucizumab + mFOLFOX-6

Vanucizumab DRUG

Vanucizumab will be administered according to dose and schedule described in respective arm.

Also known as: RO5520985

Part 1 (Induction): Vanucizumab + mFOLFOX-6; Part 1 (Maintenance): Vanucizumab + 5-FU + Folinic acid; Part 2 (Induction): Vanucizumab + mFOLFOX-6; Part 2 (Maintenance): Vanucizumab + 5-FU + Folinic acid

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed mCRC not amenable to potentially curative resection with at least one measurable metastatic lesion, as defined by RECIST v1.1
• Eastern Cooperative Oncology Group (World Health Organization) performance status of 0 or 1
• Adequate hematologic, liver, coagulation, renal, and cardiovascular function
• Recovery from all reversible AEs of previous medical therapies to baseline or National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 1, except for alopecia (any grade)
• Negative serum pregnancy test within 7 days prior to starting study treatment in premenopausal women and women less than (\< 2) years after the onset of menopause

You may not qualify if:

• Any prior systemic therapy (including chemotherapy, antibody therapy, tyrosine kinase inhibitors, immunotherapy, hormonal therapy) before Day 1 of Cycle 1 for treatment of mCRC
• Malignancies other than CRC within 5 years prior to randomization, except for those with a minimal risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ treated surgically with curative intent
• Radiotherapy within 28 days and abdominal/ pelvic radiotherapy within 60 days prior to Day 1 of Cycle 1, except palliative radiotherapy to bone lesions within 7 days prior to Day 1 of Cycle 1
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to Day 1 of Cycle
• Pregnant or lactating women
• Symptomatic central nervous system (CNS) metastases or carcinomatous meningitis. Asymptomatic patients must be clinically stable with regard to their CNS/ meningeal metastatic involvement, have completed previous therapy (including radiation and/ or surgery) at least 4 weeks prior to study drug administration, are not receiving steroid therapy or taper, and are not receiving anti-convulsive medication for any CNS involvement
• Active infection requiring IV antibiotics
• Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids, or the equivalent of less than or equal to (\</=) 10 mg/day prednisone
• Sensory peripheral neuropathy greater than or equal to (\>/=) Grade 2
• Significant cardiovascular or cerebrovascular disease within 6 months prior to Day 1 of Cycle 1
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation
• Current use of anticoagulants at therapeutic doses within 7 days prior to study drug administration. Prophylactic use of unfractioned heparin or low molecular weight heparin is permitted
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to Day 1 of Cycle 1
• History of intra-abdominal inflammatory process within 6 months prior to Day 1 of Cycle 1 including but not limited to peptic ulcer disease, diverticulitis, or colitis
• Colonic prosthesis (stent) implant in place

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (39)

Alabama Oncology

Birmingham, Alabama, 35211, United States

Location

Arizona Clinical Research Ctr

Tucson, Arizona, 85715, United States

Location

California Cancer Associates for Research & Excellence, Inc.

Encinitas, California, 92008, United States

Location

Fresno cCare

Fresno, California, 93720, United States

Location

University of California San Diego Medical Center

La Jolla, California, 92093-5354, United States

Location

Va Greater Los Angeles Healthcare System

Sepulveda, California, 91343, United States

Location

SCRI Florida Cancer Specialists South

Fort Myers, Florida, 33916, United States

Location

Ocala Oncology Center

Ocala, Florida, 34471, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Oncology Hematology Care Inc

Cincinnati, Ohio, 45242, United States

Location

Sarah Cannon Research Inst.

Nashville, Tennessee, 37203, United States

Location

Ctr for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

Cancer Therapy & Research Center

San Antonio, Texas, 78229, United States

Location

Northern Utah Associates

Ogden, Utah, 84403, United States

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

The Queen Elizabeth Hospital

Woodville, South Australia, 5011, Australia

Location

Monash Medical Centre-Moorabbin Campus

Clayton, Victoria, 3168, Australia

Location

Salzburger Landeskliniken LKH

Salzburg, 5020, Austria

Location

Oö. Gesundheits- und Spitals-AG/LKH Steyr

Steyr, 4400, Austria

Location

Imeldaziekenhuis

Bonheiden, 2820, Belgium

Location

Centre Paul Papin

Angers, 49055, France

Location

Institut De Cancerologie De L'Ouest; Medical Oncology

Saint-Herblain, 44115, France

Location

Hospital Universitario Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, 14004, Spain

Location

Hospital del Mar; Servicio de Oncologia

Barcelona, 08003, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, 28007, Spain

Location

Hospital Universitario Clínico San Carlos; Servicio de Oncologia

Madrid, 28040, Spain

Location

HM Sanchinarro - CIOCC; Servicio de Oncologia

Madrid, 28050, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Aberdeen Royal Infirmary; Medical Oncology Dept

Aberdeen, AB25 2ZN, United Kingdom

Location

Guys and St Thomas NHS Foundation Trust, Guys Hospital

London, SE1 9RT, United Kingdom

Location

Maidstone Hospital

Maidstone, ME16 9QQ, United Kingdom

Location

Queen's Hospital; Oncology

Romford, RM7 0AG, United Kingdom

Location

The Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Bevacizumab; Leucovorin; Oxaliplatin; vanucizumab

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2014
• First Posted: May 19, 2014
• Study Start: June 30, 2014
• Primary Completion: July 29, 2016
• Study Completion: February 1, 2017
• Last Updated: March 25, 2020
• Results First Posted: March 25, 2020

Record last verified: 2020-03

Locations

ES (12); BE (1); FR (2); GB (5); AU (3); US (14)