A Study of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Gastroesophageal Junction or Gastric Cancer (JACOB)

Roche

Status and phase: Completed; Phase 3

Conditions: Gastric Cancer

Treatments: Drug: Pertuzumab; Drug: Trastuzumab; Drug: Capecitabine; Drug: 5-Fluorouracil; Drug: Cisplatin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01774786

BO25114

2012-003554-83 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 780 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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780 participants in 2 patient groups, including a placebo group

Pertuzumab + Trastuzumab + Chemotherapy

Experimental group

Description:

Participants 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). Thereafter, participants will continue to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Treatment:

Drug: 5-Fluorouracil

Drug: Cisplatin

Drug: Trastuzumab

Drug: Pertuzumab

Drug: Capecitabine

Placebo + Trastuzumab + Chemotherapy

Placebo Comparator group

Description:

Participants will receive placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine \[capecitabine or 5-fluorouracil\]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Treatment:

Drug: 5-Fluorouracil

Drug: Cisplatin

Drug: Trastuzumab

Drug: Placebo

Drug: Capecitabine