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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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01774786
First received: January 21, 2013
Last updated: November 1, 2016
Last verified: November 2016
  Purpose
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.

Condition Intervention Phase
Gastric Cancer
Drug: 5-Fluorouracil
Drug: Capecitabine
Drug: Cisplatin
Drug: Pertuzumab
Drug: Placebo
Drug: Trastuzumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Baseline up to death (up to approximately 8.5 years) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline up to approximately 8.5 years ] [ Designated as safety issue: No ]
  • Percentage of Participants With Left Ventricular Systolic Dysfunction (Symptomatic or Asymptomatic) [ Time Frame: Baseline up to approximately 8.5 years ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: Yes ]

Enrollment: 780
Study Start Date: June 2013
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pertuzumab + Trastuzumab + Chemotherapy
\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.
Drug: 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.
Drug: 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.
Drug: Cisplatin
Participants will receive cisplatin 80 mg/m^2 IV q3w for 6 cycles.
Drug: Pertuzumab
Participants will receive pertuzumab 840 mg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Other Name: Perjeta
Drug: Placebo
Participants will receive pertuzumab placebo IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Drug: Trastuzumab
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.
Other Name: Herceotin
Placebo Comparator: Placebo + Trastuzumab + Chemotherapy
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.
Drug: 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.
Drug: 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.
Drug: Cisplatin
Participants will receive cisplatin 80 mg/m^2 IV q3w for 6 cycles.
Drug: Pertuzumab
Participants will receive pertuzumab 840 mg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Other Name: Perjeta
Drug: Placebo
Participants will receive pertuzumab placebo IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Drug: Trastuzumab
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.
Other Name: Herceotin

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01774786

  Show 192 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01774786     History of Changes
Other Study ID Numbers: BO25114  2012-003554-83 
Study First Received: January 21, 2013
Last Updated: November 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Pertuzumab
Cisplatin
Trastuzumab
Fluorouracil
Capecitabine
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 08, 2016