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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

NCT01774786

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title:A Study of Perjeta (Pertuzumab) in Combination With Herceptin (Trastuzumab) and Chemotherapy in Patients With HER2-Positive Metastatic Gastroesophageal Junction or Gastric Cancer
  • Official Title:A DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED, MULTICENTER PHASE III STUDY EVALUATING THE EFFICACY AND SAFETY OF PERTUZUMAB IN COMBINATION WITH TRASTUZUMAB AND CHEMOTHERAPY IN PATIENTS WITH HER2-POSITIVE METASTATIC GASTROESOPHAGEAL JUNCTION OR GASTRIC CANCER

Clinical Trial IDs

  • ORG STUDY ID: BO25114
  • NCT ID: NCT01774786

Trial Conditions

  • Gastric Cancer

Trial Interventions

DrugSynonymsArms
5-fluorouracilPertuzumab + TFP
capecitabinePertuzumab + TFP
cisplatinPertuzumab + TFP
pertuzumab [Perjeta]Pertuzumab + TFP
placeboPlacebo + TFP
trastuzumab [Herceptin]Pertuzumab + TFP

Trial Purpose

This double-blind, placebo-controlled, randomized, multicenter, international, parallel arm study will evaluate the efficacy and safety of Perjeta (pertuzumab) in combination with Herceptin (trastuzumab), fluoropyrimidine and cisplatin as first-line treatment in patients with HER2-positive metastatic gastroesophageal junction or gastric cancer. Patients will be randomized to receive Perjeta 840 mg or placebo intravenously (iv) every 3 weeks in combination with Herceptin (initial dose of 8 mg/kg iv followed by 6 mg/kg iv every 3 weeks) and cisplatin and fluoropyrimidine (capecitabine or 5-fluorouracil) for the first 6 treatment cycles. Patients will continue to receive Perjeta or placebo and Herceptin until disease progression or unacceptable toxicity occurs.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Pertuzumab + TFPExperimental
  • 5-fluorouracil
  • capecitabine
  • cisplatin
  • pertuzumab [Perjeta]
    • trastuzumab [Herceptin]
Placebo + TFPPlacebo Comparator
  • 5-fluorouracil
  • capecitabine
  • cisplatin
    • placebo
    • trastuzumab [Herceptin]

Eligibility Criteria

Inclusion Criteria:

- Adult patients, >/= 18 years of age

- HER2-positive metastatic adenocarcinoma of the stomach or gastroesophageal junction

- 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 >/= 3 months

Exclusion Criteria:

- Previous cyctotoxic 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 peripheral bone metastases, if recovered from all toxicities)

- History or evidence of brain metastases

- Clinically significant active GI bleeding (Grade >/= 2 according to NIC-CTCAEv.4.03)

- Other malignancy (in addition to 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 < 55%

- Any significant uncontrolled intercurrent systemic illness

- Positive for hepatitis B, hepatitis C or HIV infection

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival: Time from randomization to death of any cause
Time Frame:approximately 4.5 years
Safety Issue:No
Description:

Secondary Outcome Measures

Measure:Progression-free survival: Time from randomization to first occurrence of disease progression, as determined by the investigator according to RECIST v1.1 criteria, or death of any cause
Time Frame:approximately 4.5 years
Safety Issue:No
Description:
Measure:Overall objective response (partial response + complete response) occurring on two consecutive occasions >/= 4 weeks apart, as determined by the investigator according to RECIST v1.1 criteria
Time Frame:approximately 4.5 years
Safety Issue:No
Description:
Measure:Duration of objective response: Time from occurrence of objective response to progressive disease, as determined by investigator according to RECIST v1.1 criteria, or death of any cause
Time Frame:approximately 4.5 years
Safety Issue:No
Description:
Measure:Clinical benefit rate: Best response of complete response or partial response or stable disease for 6 weeks or longer, as determined by the investigator according to RECIST v1.1 criteria
Time Frame:approximately 4.5 years
Safety Issue:No
Description:
Measure:Safety: Incidence of adverse events
Time Frame:approximately 4.5 years
Safety Issue:No
Description:
Measure:Safety: Incidence of left ventricular systolic dysfunction (symptomatic or asymptomatic)
Time Frame:approximately 4.5 years
Safety Issue:Yes
Description:

Trial Keywords