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

• Register: EUCTR
• Last refreshed on: 27 July 2020
• Main ID: EUCTR2012-001402-23-GB
• Date of registration: 12/07/2012
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public 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
• Scientific 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
• Date of first enrolment: 03/09/2012
• Target sample size: 800
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001402-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd.

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
• Male or female, 18 years of age or older
• ECOG performance status of 0 or 1
• Life expectancy > 3 months
• Histologically confirmed adenocarcinoma of the stomach or GEJ with inoperable metastatic disease not amenable to curative therapy
• Adequate archival or newly obtained formalin-fixed paraffin-embedded (FFPE) tissue for central IHC assay of Met receptor and HER2 status
• Tumor (either primary or metastatic lesion) defined as Met positive by IHC (= 50% of tumor cells with membrane and/or cytoplasmic staining at weak, moderate, or high intensity)
• Measurable disease or non-measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Patients with peritoneal disease would generally be regarded as having evaluable disease and be allowed to enter the trial.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 600
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion criteria:
• HER2-positive tumor (primary tumor or metastasis)
HER2-positivity is defined as either IHC 3+ or IHC 2+/ISH+; ISH positivity is defined as a HER2:CEP17 ratio of = 2.0.
• Previous chemotherapy for locally advanced or metastatic gastric carcinoma Patients may have received either neoadjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to randomization.
• Prior exposure to experimental treatment targeting either the HGF or Met pathway
• History of another malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, localized prostate cancer that has been treated surgically with curative intent and presumed cured, or other malignancies with an expected curative outcome
Hematologic, Biochemical, and Organ Function
• Granulocyte count < 1500/mm3, platelet count < 100,000/mm3, and hemoglobin < 9.0 g/dL within 7 days prior to enrollment
• Partial thromboplastin time (PTT), international normalized ratio (INR), or prothrombin time (PT) > 1.5 x the upper limit of normal (ULN), except for patients receiving anticoagulation therapy
• AST (SGOT), ALT (SGPT), alkaline phosphatase (ALP) = 2.5 × ULN (= 5 × ULN with liver metastases)
• Total bilirubin = 1.5 × ULN (except in patients diagnosed with Gilbert’s disease)
• Serum calcium > ULN (corrected for low serum albumin concentrations) Corrected calcium (mg/dL) = serum Ca2+ + [(4.0–measured serum albumin) x 0.8] Corrected calcium (mmol/L) = serum Ca2+ + 0.02 × (40–serum albumin)
• Serum creatinine > 1.5 × ULN or calculated creatinine clearance < 60 mL/min (Cockcroft and Gault 1976)
• Uncontrolled diabetes as evidenced by fasting serum glucose level > 200 mg/dL
• Clinically significant gastrointestinal abnormalities, apart from gastric cancer, including uncontrolled inflammatory gastrointestinal diseases (Crohn’s disease, ulcerative colitis, etc.)
• Known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV), or known HIV-seropositivity.
• Major surgery within 4 weeks before start of study treatment, without complete recovery


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Gastroesophageal cancer
MedDRA version: 15.0 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 15.0 Level: LLT Classification code 10066354 Term: Adenocarcinoma of the gastroesophageal junction System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: MetMAb (600mg/10ml)
Product Code: Ro 549-0258/F01-01
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Onartuzumab
CAS Number: 1133766-06-9
Current Sponsor code: RO5490258/PRO143966
Other descriptive name: One Armed anti-cMet, OA5D5, c-Met, Anti-Met
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Product Name: MetMAb (900mg/15ml)
Product Code: Ro 549-0258/F02-01
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Onartuzumab
CAS Number: 1133766-06-9
Current Sponsor code: RO5490258/PRO143966
Other descriptive name: One Armed anti-cMet, OA5D5, c-Met, Anti-Met
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: • To evaluate the efficacy of onartuzumab + mFOLFOX6 relative to placebo + mFOLFOX6 as measured by PFS and ORR in the Met 2+/3+ subgroup and in the ITT population
• To evaluate the safety of onartuzumab + mFOLFOX6 compared with placebo + mFOLFOX6 in patients with metastatic HER2-negative, Met-positive GEC, focusing on all adverse events, National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.0) Grade = 3 adverse events, and
Grade = 3 laboratory toxicities
• To compare patient-reported outcomes (PROs) following treatment with onartuzumab + mFOLFOX6 relative to placebo + mFOLFOX6, as measured by the EORTC QLQ-C30 and its gastric cancer module (the QLQ-STO22).
• To characterize the pharmacokinetics of onartuzumab when given with mFOLFOX6
• To evaluate serum levels and incidence of anti-therapeutic antibodies (ATAs) against onartuzumab

Timepoint(s) of evaluation of this end point: OS is defined as the time from randomization to death to any cause

Main Objective: • To evaluate the efficacy of onartuzumab + mFOLFOX6 compared with placebo + mFOLFOX6 as measured by overall survival (OS) in patients with previously untreated HER2–negative metastatic gastroesophageal cancer (GEC) classified as Met IHC 2+ or 3+ (Met 2+/3+ subgroup)
• To evaluate the efficacy of onartuzumab + mFOLFOX6 compared with placebo + mFOLFOX6 as measured by OS in patients with previously untreated HER2 negative metastatic GEC classified as Met-IHC 1+, 2+, or 3+ (intent-to-treat [ITT] population)

Primary end point(s): • One interim efficacy and futility analysis planned for the Met 2+/3+ subgroup occurring at the time of the ITT final analysis, which is triggered by obtaining 67% of total OS information (79 events) from the Met 2+/3+ subgroup and 449 events from the ITT population
• Final efficacy analysis for the 2+/3+ subgroup triggered by 118 OS events (this will likely occur after the final analysis of the ITT population)

Secondary Outcome(s)

Secondary end point(s): Progression-Free Survival, ORR, Safety, PK and PRO

Timepoint(s) of evaluation of this end point: Final analysis

Secondary ID(s)

YO28322

2012-001402-23-ES

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd.

Ethics review

Status: Approved
Approval date: 03/09/2012
Contact:

Results

• Results available: Yes
• Date Posted: 29/12/2016
• Date Completed: 15/12/2015
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-001402-23/results