Overview

This trial is active, not recruiting.

Condition gastric cancer
Treatments 5-fluorouracil, capecitabine, cisplatin, pertuzumab, placebo, trastuzumab
Phase phase 3
Targets HER2, HER
Sponsor Hoffmann-La Roche
Start date June 2013
End date December 2021
Trial size 780 participants
Trial identifier NCT01774786, 2012-003554-83, BO25114

Summary

This double-blind, placebo-controlled, randomized, multicenter, international, parallel arm study will evaluate the efficacy and safety of pertuzumab in combination with trastuzumab, fluoropyrimidine and cisplatin as first-line treatment in participants with HER2-positive metastatic gastroesophageal junction (GEJ) or gastric cancer (GC). Participants will be randomized to receive pertuzumab 840 milligrams (mg) or placebo intravenously every 3 weeks (q3w) in combination with trastuzumab (initial dose of 8 milligrams per kilogram [mg/kg] intravenously [IV] followed by 6 mg/kg IV q3w) and cisplatin and fluoropyrimidine (capecitabine or 5-fluorouracil) for the first 6 treatment cycles. Participants will continue to receive pertuzumab or placebo and trastuzumab until disease progression occurrence of unacceptable toxicity or withdrawal from the study for another reason.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
\nParticipants will receive pertuzumab in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Participants will continue to receive pertuzumab and trastuzumab until disease progression occurrence of unacceptable toxicity or withdrawal from the study for another reason.
5-fluorouracil
Participants will receive 5-fluorouracil 800 milligrams per meter square (mg/m^2)/24 hour IV infusion for 120 hours (Days 1-5) q3w for 6 cycles.
capecitabine
Participants will receive capecitabine 1000 mg/m^2 orally twice daily, evening of Day 1 to morning of Day 15 (28 doses) q3w for 6 cycles.
cisplatin
Participants will receive cisplatin 80 mg/m^2 IV q3w for 6 cycles.
pertuzumab Perjeta
Participants will receive pertuzumab 840 mg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
placebo
Participants will receive pertuzumab placebo IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
trastuzumab Herceotin
Participants will receive 8 mg/kg IV initial dose on Day 1, followed by 6 mg/kg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
(Placebo Comparator)
Participants will receive pertuzumab placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine [capecitabine or 5-fluorouracil]) for the first 6 treatment cycles (cycle length = 21 days). Participants will continue to receive pertuzumab placebo and trastuzumab until disease progression occurrence of unacceptable toxicity or withdrawal from the study for another reason.
5-fluorouracil
Participants will receive 5-fluorouracil 800 milligrams per meter square (mg/m^2)/24 hour IV infusion for 120 hours (Days 1-5) q3w for 6 cycles.
capecitabine
Participants will receive capecitabine 1000 mg/m^2 orally twice daily, evening of Day 1 to morning of Day 15 (28 doses) q3w for 6 cycles.
cisplatin
Participants will receive cisplatin 80 mg/m^2 IV q3w for 6 cycles.
pertuzumab Perjeta
Participants will receive pertuzumab 840 mg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
placebo
Participants will receive pertuzumab placebo IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
trastuzumab Herceotin
Participants will receive 8 mg/kg IV initial dose on Day 1, followed by 6 mg/kg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Primary Outcomes

Measure
Overall Survival
time frame: Baseline up to death (up to approximately 8.5 years)

Secondary Outcomes

Measure
Progression-Free Survival, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria
time frame: Baseline up to death or disease progression, whichever occurs first (up to approximately 8.5 years)
Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria
time frame: Baseline up to death or disease progression, whichever occurs first (up to approximately 8.5 years)
Duration of Objective Response, as Determined by Investigator According to RECIST v1.1 Criteria
time frame: Baseline up to death or disease progression, whichever occurs first (up to approximately 8.5 years)
Percentage of Participants With Clinical Benefit, as Determined by the Investigator According to RECIST v1.1 Criteria
time frame: Baseline up to death or disease progression, whichever occurs first (up to approximately 8.5 years)
Percentage of Participants With Adverse Events
time frame: Baseline up to approximately 8.5 years
Percentage of Participants With Left Ventricular Systolic Dysfunction (Symptomatic or Asymptomatic)
time frame: Baseline up to approximately 8.5 years
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) Questionnaire Score
time frame: Day 1 of each 21-day treatment cycle up to 28 and 60-90 days after Day 1 of last treatment cycle (up to approximately 8.5 years)
EORTC QLQ-Gastric Cancer Module (EORTC QCQ-STO22) Questionnaire Score
time frame: Day 1 of each 21-day treatment cycle up to 28 and 60-90 days after Day 1 of last treatment cycle (up to approximately 8.5 years)
European Quality of Life - 5 Dimensions (EQ-5D) Questionnaire Score
time frame: Day 1 of each 21-day treatment cycle up to 28 and 60-90 days after Day 1 of last treatment cycle (up to approximately 8.5 years)
Maximum Serum Concentrations (Cmax) of Pertuzumab\n
time frame: Pre-dose (0-6 hours [Hr] before infusion) on Day 1 (D1) of Cycles (Cy) 1, 2, 3, 4, 6, 8; 0.5 Hr after end of 30-60 minutes infusion on D1 of Cy 1, 2, 4, 8; at 28 & 60-90 days after D1 of last Cy (up to approximately 8.5 years) (1 cycle = 21 days)
Cmax of Trastuzumab
time frame: Pre-dose (0-6 hours [Hr] before infusion) on Day 1 (D1) of Cycles (Cy) 1, 2, 3, 4, 6, 8; 0.5 Hr after end of 30-60 minutes infusion on D1 of Cy 1, 2, 4, 8; at 28 & 60-90 days after D1 of last Cy (up to approximately 8.5 years) (1 cycle = 21 days)
Minimum Serum Concentration (Cmin) of Pertuzumab
time frame: Pre-dose (0-6 Hr before infusion) on D1 of Cy 1, 2, 3, 4, 6, 8; at 28 & 60-90 days after D1 of last Cy (up to approximately 8.5 years) (1 cycle = 21 days)
Cmin of Trastuzumab
time frame: Pre-dose (0-6 Hr before infusion) on D1 of Cy 1, 2, 3, 4, 6, 8; at 28 & 60-90 days after D1 of last Cy (up to approximately 8.5 years) (1 cycle = 21 days)
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Pertuzumab
time frame: Pre-dose (0-6 Hr before infusion) on Day 1 of Cycles 1, 3, 6; at 28 & 60-90 days after D1 of last Cy (up to approximately 8.5 years) (1 cycle = 21 days)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically confirmed metastatic adenocarcinoma of the stomach or GEJ - Measurable or evaluable non-measurable disease as assessed by the investigator according to RECIST v1.1 criteria - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Life expectancy greater than equal to (>/=) 3 months Exclusion Criteria: - Previous cytotoxic chemotherapy for advanced (metastatic) disease - Evidence of disease progression documented within 6 months after completion of prior neoadjuvant or adjuvant cytotoxic chemotherapy, or both, or radiotherapy for GEJ adenocarcinoma - Previous treatment with any HER2-directed therapy, at any time, for any duration - Previous exposure to any investigational treatment within 30 days before the first dose of study treatment - Radiotherapy within 30 days before the first dose of study treatment (within 2 weeks if given as palliation to bone metastases, if recovered from all toxicities) - History or evidence of brain metastases - Clinically significant active gastrointestinal (GI) bleeding (Grade >/=2 according to National Cancer Institute [NIC]-Common Terminology Criteria for Adverse Events Version 4.0 [CTCAEv.4.0]) - Residual toxicity resulting from previous therapy (for example, hematologic, cardiovascular, or neurologic toxicity that is Grade >/=2). Alopecia is permitted - Other malignancy (in addition to gastric cancer [GC]) within 5 years before enrollment, except for carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin that has been previously treated with curative intent - Inadequate hematologic, renal or liver function - Pregnant or lactating women - History of congestive heart failure of any New York Heart Association (NYHA) criteria - Angina pectoris requiring treatment - Myocardial infarction within the past 6 months before the first dose of study drug - Clinically significant valvular heart disease or uncontrollable high-risk cardiac arrhythmia - History or evidence of poorly controlled hypertension - Baseline left ventricular ejection fraction (LVEF) value less than (<) 55 percent (%) - Any significant uncontrolled intercurrent systemic illness - Positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection

Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.