A Study of Onartuzumab in Combination With mFOLFOX6 in Participants With Metastatic HER2-Negative and MET-Positive Gastroesophageal Cancer

Gastric Cancer Clinical Trial

Official title:

A Randomized, Phase III, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Onartuzumab (MetMAb) in Combination With 5-Fluorouracil, Folinic Acid, and Oxaliplatin (mFOLFOX6) in Patients With Metastatic HER2-Negative, MET-Positive Gastroesophageal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01662869
• Other study ID #: YO28322
• Secondary ID: 2012-001402-23
• Status: Completed
• Phase: Phase 3
• First received: August 8, 2012
• Last updated: November 1, 2016
• Start date: November 2012
• Est. completion date: December 2015

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This randomized, multicenter, double-blind, placebo-controlled study will evaluate the efficacy and safety of onartuzumab (MetMAb) in combination with 5-fluorouracil, folinic Acid, and oxaliplatin (mFOLFOX6) in participants with metastatic human epidermal growth receptor (HER) 2-negative and MET-positive adenocarcinoma of the stomach or gastroesophageal junction. Participants will be randomized in a 1:1 ratio to receive either onartuzumab or placebo in combination with mFOLFOX6. Participants may continue to receive onartuzumab or placebo until disease progression, unacceptable toxicity, participant or physician decision to discontinue treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 564
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adenocarcinoma of the stomach or gastroesophageal junction with inoperable, metastatic disease, not amenable to curative therapy

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Life expectancy greater than (>) 3 months

• Presence of tissue sample for IHC assay of MET receptor and HER2 status

• Tumor (primary or metastatic lesion) defined as MET-positive by IHC

• Measurable disease or non-measurable but evaluable disease, according to the RECIST v1.1; Participants with peritoneal disease would generally be regarded as having evaluable disease and allowed to enter the trial

• For women who are not postmenopausal or surgically sterile; agreement to use an adequate method of contraception (hormonal implant) during the treatment period and for at least 90 days after the last dose of onartuzumab/placebo and 6 months after the last dose of oxaliplatin

• For men: agreement to use a barrier method of contraception during the treatment period and for 90 days after the last dose of onartuzumab/placebo and 6 months after the last dose of oxaliplatin

Exclusion Criteria:

• HER2-positive tumor (primary tumor or metastasis)

• Previous chemotherapy for locally advanced or metastatic gastric carcinoma (adjuvant or neoadjuvant chemotherapy must be completed at least 6 months prior to randomization)

• Prior treatment with investigational drugs that target the human growth factor (HGF) or MET pathway

• History of another malignancy within the previous 5 years, except for appropriately treated and presumed cured carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, and localized prostate cancer

• Pregnancy or lactation

• Receipt of an investigational drug within 28 days prior to study start

• Clinically significant gastrointestinal abnormalities, apart from gastric cancer, including uncontrolled inflammatory gastrointestinal diseases

• Significant history of cardiac disease

• Significant vascular disease

• Serious active infection at the time of randomization, or other serious underlying medical conditions that would impair the ability of the participant to receive protocol treatment

• Infection with human immunodeficiency virus, hepatitis B, or hepatitis C

• Radiotherapy within 4 weeks before start of study treatment

• Major surgery within 4 weeks before start of study treatment, without complete recovery

• Any condition (psychological, geographical) that does not permit compliance with study and follow-up procedures

• Peripheral neuropathy

• Prior unanticipated severe reaction to fluoropyrimidine therapy

• Known sensitivity or contraindication to any component of study treatment

• Active gastrointestinal bleeding

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• 5-Fluoruracil
Participants will receive 5-fluorouracil 400 milligrams per square meter (mg/m^2) IV bolus and then 2400 mg/m^2 as a continuous IV infusion over 46-48 hours on Day 1 of every cycle until disease progression or at the maximum of 12 cycles, whichever occurs first.
• Folinic acid
Participants will receive folinic acid 400 mg/m^2 IV infusion over 2 hours on Day 1 of every cycle until disease progression or at the maximum of 12 cycles, whichever occurs first.
• Onartuzumab
Participants will receive onartuzumab 10 mg/kg IV infusion on Day 1 of every cycle (each cycle = 14 days) until disease progression, unacceptable toxicity, or participant or physician decision to discontinue treatment.
• Oxaliplatin
Participants will receive oxaliplatin 85 mg/m^2 IV infusion over 2 hours on Day 1 of every cycle until disease progression or at the maximum of 12 cycles, whichever occurs first.
• Placebo
Participants will receive onartuzumab matching placebo on Day 1 of every cycle (each cycle = 14 days) until disease progression, unacceptable toxicity, or participant or physician decision to discontinue treatment.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czech Republic,  France,  Germany,  Guatemala,  Hong Kong,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Mexico,  Panama,  Poland,  Russian Federation,  Singapore,  Spain,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS) in the MET Immunohistochemistry (IHC) 2+/3+ Participant Subgroup		Baseline until death (up to approximately 38 months overall)	No
Primary	OS in the Intent-To-Treat (ITT) Population		Baseline until death (up to approximately 38 months overall)	No
Secondary	Duration of Response, as Assessed by Investigator Using RECIST v1.1		Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 6 weeks for 12 months and thereafter every 12 weeks up to approximately 38 months overall)	No
Secondary	Percentage of Participants with a Tumor Response of CR or PR or Stable Disease (SD, Maintained for At Least 6 Months) as Determined by the Investigator Using RECIST v1.1		Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 6 weeks for 12 months and thereafter every 12 weeks up to approximately 38 months overall)	No
Secondary	Percentage of Participants with Adverse Events		Baseline up to approximately 38 months	No
Secondary	Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) of Onartuzumab		Pre-dose (within 1 hour before infusion start) on Day 1 of Cycles 1 and 4, (cycle length = 14 days), at study drug discontinuation visit (up to 38 months)	Yes
Secondary	Change from Baseline in ATAs Level of Onartuzumab		Baseline (pre-dose [within 1 hour before infusion start] on Cycle 1 Day 1), pre-dose on Cycle 4 Day 1 (cycle length = 14 days), at study drug discontinuation visit (up to 38 months)	No
Secondary	Minimum Serum Concentration of Onartuzumab (Cmin)		Pre-dose (within 1 hour before infusion start) on Day 1 of Cycles 1, 2 and 4, 30 minutes after end of infusion (duration of infusion = 60 minutes) on Cycle 1 Day 1 (cycle length = 14 days), at study drug discontinuation visit (up to 38 months)	No
Secondary	Maximum Serum Concentration (Cmax) of Onartuzumab		Pre-dose (within 1 hour before infusion start) on Day 1 of Cycles 1, 2 and 4, 30 minutes after end of infusion (duration of infusion = 60 minutes) on Cycle 1 Day 1 (cycle length = 14 days), at study drug discontinuation visit (up to 38 months)	No
Secondary	Progression-Free Survival (PFS), as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in MET IHC 2+/3+ Participant Subgroup		Baseline up to disease progression or death due to any cause, whichever occurs first (up to approximately 38 months overall)	No
Secondary	PFS, as Assessed by Investigator Using RECIST v1.1 in ITT Population		Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 6 weeks for 12 months and thereafter every 12 weeks up to approximately 38 months overall)	No
Secondary	Percentage of Participants with a Tumor Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator Using RECIST v1.1 in MET IHC 2+/3+ Participant Subgroup		Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 6 weeks for 12 months and thereafter every 12 weeks up to approximately 38 months overall)	No
Secondary	Percentage of Participants with a Tumor Response of CR or PR as Determined by the Investigator Using RECIST v1.1 in ITT Population		Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 6 weeks for 12 months and thereafter every 12 weeks up to approximately 38 months overall)	No
Secondary	European Organization for Research and Treatment Cancer Quality of Life Questionnaire (EORTC QLQ) Core 30 (EORTC QLQ-C30) Score		Day 1 of each treatment cycle (cycle length = 14 days) up to approximately 38 months	No
Secondary	EORTC QLQ-Gastric cancer Specific Quality of Life Questionnaire (EORTC QLQ-STOC22) Score		Day 1 of each treatment cycle (cycle length = 14 days) up to approximately 38 months	No
Secondary	European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Score		Day 1 of each treatment cycle (cycle length = 14 days) up to approximately 38 months	No