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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
197
5-FU will be administered according to dose and schedule described in respective arm.
Bevacizumab will be administered according to dose and schedule described in respective arm.
Folinic acid will be administered according to dose and schedule described in respective arm.
Oxaliplatin will be administered according to dose and schedule described in respective arm.
Vanucizumab will be administered according to dose and schedule described in respective arm.
Alabama Oncology
Birmingham, Alabama, United States
Arizona Clinical Research Ctr
Tucson, Arizona, United States
California Cancer Associates for Research & Excellence, Inc.
Encinitas, California, United States
Fresno cCare
Fresno, California, United States
University of California San Diego Medical Center
La Jolla, California, United States
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.
Time frame: Baseline, every 8 weeks, up to approximately 29 months
Percentage of Participants With Objective Response (ORR) as Assessed Using RECIST v. 1.1
Efficacy of vanucizumab was evaluated in terms of Percentage of Participants With ORR as Investigator-Assessed Using RECIST v. 1.1. Best Overall Confirmed Response.
Time frame: 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
Efficacy of vanucizumab was evaluated in terms of duration of objective response as assessed using RECIST v. 1.1. This was computed using the PFS definition with death on study (deaths that occurred outside the 30 days window from the last study treatment are excluded).
Time frame: 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)
Efficacy of vanucizumab was evaluated in terms of OS as the time from randomization until death from any cause. 99999 = data not estimable due to the low number of deaths.
Time frame: Baseline until death from any cause (maximum up to approximately 3.5 years)
Percentage of Participants With Adverse Events (AEs)
Safety is evaluated in terms of percentage of participants with at least one serious adverse event and percentage of participants with at least one adverse event.
Time frame: Up to approximately 29 months
Number of Participants With Human Anti-human Antibodies (HAHAs) Against Vanucizumab
Safety is evaluated in terms of number of participants with Human Anti-human Antibodies (HAHAs) Against Vanucizumab.
Time frame: End of study (EoS, within 28 to 42 days after last dose, latest at 29 months)
Area Under the Plasma Concentration-Time Curve (AUC) of Vanucizumab
PK profile of vanucizumab was evaluated in terms of AUC
Time frame: Cycles 1 and 8 of parts 1 and 2
Maximum Observed Plasma Concentration (Cmax) of Vanucizumab
PK profile of vanucizumab was evaluated in terms of Cmax
Time frame: Cycles 1 and 8 of parts 1 and 2
Minimum Observed Plasma Concentration (Clast) of Vanucizumab
PK profile of vanucizumab was evaluated in terms of Clast
Time frame: Cycles 1 and 8 of parts 1 and 2
Time to Reach Cmax (Tmax) of Vanucizumab
PK profile of vanucizumab was evaluated in terms of Tmax
Time frame: Cycles 1 and 8 of parts 1 and 2
Plasma Terminal Half-Life (t1/2) of Vanucizumab
PK profile of vanucizumab was evaluated in terms of t1/2, values are reported for cycle 8 of both part 1 (safety run-in) and part 2 of the study.
Time frame: Cycle 8
Plasma Clearance at Steady State (CLss) of Vanucizumab
PK profile of vanucizumab was evaluated in terms of CLss, values are reported for cycle 8 of both part 1 (safety run-in) and part 2 of the study.
Time frame: Cycle 8
Volume of Distribution at Steady State (Vss) of Vanucizumab
PK profile of vanucizumab was evaluated in terms of Vss, values are reported for cycle 8 of both part 1 (safety run-in) and part 2 of the study.
Time frame: Cycle 8
Cmax Accumulation Ratio (AR) of Vanucizumab
PK profile of vanucizumab was evaluated in terms of Cmax Ratio, values are reported for cycle 8 of both part 1 (safety run-in) and part 2 of the study.
Time frame: Cycle 8
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Va Greater Los Angeles Healthcare System
Sepulveda, California, United States
SCRI Florida Cancer Specialists South
Fort Myers, Florida, United States
Ocala Oncology Center
Ocala, Florida, United States
Duke University Medical Center
Durham, North Carolina, United States
Oncology Hematology Care Inc
Cincinnati, Ohio, United States
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