A RANDOMIZED, PHASE III, MULTICENTER, DOUBLE-BLIND, PLACEBOCONTROLLED 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: 11 April 2016
• Main ID: EUCTR2012-001402-23-IT
• Date of registration: 27/06/2012
• Prospective Registration: Yes
• Primary sponsor: F. HOFFMANN - LA ROCHE LTD.
• Public title: A RANDOMIZED, PHASE III, MULTICENTER, DOUBLE-BLIND, PLACEBOCONTROLLED 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, PLACEBOCONTROLLED 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: 26/08/2012
• 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: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: mFOLFOX6 Number of treatment arms in the trial: 2

Countries of recruitment

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

Contacts

• Name: MEDICAL AFFAIRS&CLINICAL OPERATIONS
• Affiliation: ROCHE SpA

• Name: MEDICAL AFFAIRS&CLINICAL OPERATIONS
• Affiliation: ROCHE SpA

Key inclusion & exclusion criteria

Inclusion criteria:
• Ability and willingness to provide written informed consent and to comply with the
study protocol
• 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.
• For women who are not postmenopausal (12 months of amenorrhea) or surgically sterile
(absence of ovaries and/or uterus): agreement to use an adequate method of
contraception (a method with a failure rate of < 1% per year, such as hormonal implants,
combined oral contraceptives, or a vasectomized partner) 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 at least 90 days after the last dose of onartuzumab/placebo and 6 months after the
last dose of oxaliplatin
Are the trial subjects under 18? no
Number of subjects for this age range: 0
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,
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
General
• Pregnancy or lactation
• Receipt of an investigational drug within 28 days prior to initiation of study drug
• Clinically significant gastrointestinal abnormalities, apart from gastric cancer, including
uncontrolled inflammatory gastrointestinal diseases (Crohn’s disease, ulcerative colitis, etc.)
• Significant history of cardiac disease (i.e., unstable angina, congestive heart failure,
as defined by the New York Heart Association [NYHA] as Class II, III, or IV) within 6 months
prior to Day 1 of Cycle 1, myocardial infarction within the previous year, or current cardiac
ventricular arrhythmias requiring medication
• Significant vascular disease (such as aortic aneurysm requiring surgical repair or recent
peripheral arterial thrombosis) within 6 months prior to Day 1 of Cycle 1
• Serious (Grade = 3) active infection at the time of randomization, or other serious
underlying medical conditions that would impair the ability of the patient to receive
protocol treatment
• Known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV),
or hepatitis C virus (HCV), or known HIV-seropositivity.
• Radiotherapy within 4 weeks before start of study treatment (2-week interval allowed
following palliative radiotherapy given to peripheral bone metastatic site and patient has
recovered from all acute toxicities)
• Major surgery within 4 weeks before start of study treatment, without complete recovery
• Any condition (e.g., psychological, geographical, etc.) that does not permit compliance with
study and follow-up procedures
• Peripheral neuropathy (NCI CTCAE v4.0, Grade > 1)
Et al.


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

Health Condition(s) or Problem(s) studied

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

Gastroesophageal cancer
MedDRA version: 14.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: LLT Classification code 10066354 Term: Adenocarcinoma of the gastroesophageal junction System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: MetMab
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/g milligram(s)/gram
Concentration type: equal
Concentration number: 600-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Product Name: MetMab
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/g milligram(s)/gram
Concentration type: equal
Concentration number: 900-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

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 the2+/3+ subgroup triggered by 118 OS
events (this will likely occur after the final analysis of the ITT
population)

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 HER2-negative metastatic 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
Et al.

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

Secondary Outcome(s)

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

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

Secondary ID(s)

YO28322

2012-001402-23-ES

Source(s) of Monetary Support

F. HOFFMANN - LA ROCHE LTD.