Phase 3 N=780 Randomized Double-blind Treatment

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

Gastric Cancer

Bottom Line

View on ClinicalTrials.gov: NCT01774786 ↗

Enrolled (actual)

780

Serious AEs

43.2%

Results posted

Feb 2018

Primary outcome: Primary: Overall Survival — 17.5; 14.2; 18.1; 14.2 Months — p=0.0565

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: 5-Fluorouracil (Drug); Capecitabine (Drug); Cisplatin (Drug); Pertuzumab (Drug); Placebo (Drug); Trastuzumab (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Hoffmann-La Roche
Primary completion: Dec 2016

Outcome Measures

Outcome	Result	p-value
PRIMARY Overall Survival	17.5; 14.2; 18.1; 14.2	0.0565
SECONDARY Progression-Free Survival, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria	8.5; 7.0; 8.5; 7.2	—
SECONDARY Primary Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria	56.7; 48.3; 5.1; 0.9; 51.6; 47.4	—
SECONDARY Final Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria	57.0; 48.6; 5.7; 2.0; 51.3; 46.6	—
SECONDARY Duration of Objective Response, as Determined by Investigator According to RECIST v1.1 Criteria	10.2; 8.4; 10.2; 8.4	—
SECONDARY Percentage of Participants With Clinical Benefit, as Determined by the Investigator According to RECIST v1.1 Criteria	84.6; 81.3	—
SECONDARY Overview of Safety: Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03	381; 385; 27; 31; 178; 156	—
SECONDARY Number of Participants With Symptomatic or Asymptomatic Left Ventricular Systolic Dysfunction (LVSD)	3; 1; 20; 18	—
SECONDARY Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score	26.68; 27.59; 6.57; 0.97; 3.63; 3.81	—
SECONDARY Change From Baseline in EORTC QLQ-Gastric Cancer Module (EORTC QLQ-STO22) Score	40.10; 40.48; -2.58; -4.11; -4.14; -3.87	—
SECONDARY Maximum Serum Concentration (Cmax) of Pertuzumab	258; 288; 341; 371	—
SECONDARY Cmax of Trastuzumab	142; 139; 120; 120; 127; 129	—
SECONDARY Minimum Serum Concentration (Cmin) of Pertuzumab	NA; 42.4; 74.0; 90.4; 114; 142	—
SECONDARY Cmin of Trastuzumab	NA; NA; 15.4; 17.2; 19.9; 20.7	—

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.

Eligibility Criteria

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01774786). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.