A Study of Pertuzumab in Combination With Trastuzumab and Chemotherapy in Patients With HER2-Positive Advanced Gastric Cancer

Study Overview
=================
Brief Summary
-----------------
This randomized, multicenter, open-label study will evaluate two different doses of pertuzumab in combination with Herceptin (trastuzumab) and chemotherapy in the first-line treatment of participants with metastatic HER2-positive adenocarcinoma of the stomach or gastroesophageal junction. Participants will be randomized in a 1:1 ratio to two treatment arms. Participants in the Pertuzumab 840/420 mg Arm will receive a pertuzumab loading dose of 840 mg for Cycle 1 and a dose of 420 mg for Cycles 2-6, and participants in the Pertuzumab 840/840 mg Arm will receive pertuzumab 840 mg for all six cycles. Participants in both treatment arms will receive trastuzumab, cisplatin, and capecitabine.

Official Title
-----------------
An Open-Label, Randomized, Multicenter Phase IIa Study Evaluating Pertuzumab in Combination With Trastuzumab and Chemotherapy in Patients With HER2-Positive Advanced Gastric Cancer

Conditions
-----------------
Gastric Cancer

Intervention / Treatment
-----------------
* Drug: Capecitabine
* Drug: Cisplatin
* Drug: Pertuzumab
* Drug: Pertuzumab
* Drug: Trastuzumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult participants, greater than or equal to (>=) 18 of age Adenocarcinoma of the stomach or gastroesophageal junction with inoperable locally advanced or metastatic disease, not amenable to curative therapy Measurable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 HER2-positive tumor Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Life expectancy of at least 3 months Exclusion Criteria: Previous chemotherapy for advanced or metastatic disease (except (prior adjuvant or neoadjuvant therapy at least 6 months before enrollment in the study) Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome Active (significant or uncontrolled) gastrointestinal bleeding Abnormal laboratory values

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pertuzumab 840/420 mg<br>Participants received pertuzumab as an intravenous (IV) infusion at a loading dose of 840 milligrams (mg) for cycle 1 and a dose of 420 mg every three weeks (Q3W) for cycles 2-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 milligram per meter squared (mg/m^2) was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 milligram per kilogram (mg/kg) Q3W for subsequent cycles. | Drug: Capecitabine<br>* 1000 mg/m2 twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle<br>* Other names: Xeloda;Drug: Cisplatin<br>* 80 mg/m2 on Day 1 of each cycle<br>Drug: Pertuzumab<br>* loading dose of 840 mg, then 420 mg once every three weeks<br>* Other names: Perjeta;Drug: Trastuzumab<br>* loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg for subsequent cycles<br>* Other names: Herceptin;|
| Experimental: Pertuzumab 840/840 mg<br>Participants received 840 mg as an IV infusion Q3W for cycles 1-6. Participants in both arms received trastuzumab, cisplatin, and capecitabine. Capecitabine 1000 mg/m^2 was administered orally twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle. Cisplatin 80 mg/m^2 was administered as an IV infusion on Day 1 of each cycle. Trastuzumab was administered as an IV infusion at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg Q3W for subsequent cycles. | Drug: Capecitabine<br>* 1000 mg/m2 twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle<br>* Other names: Xeloda;Drug: Cisplatin<br>* 80 mg/m2 on Day 1 of each cycle<br>Drug: Pertuzumab<br>* 840 mg once every three weeks<br>* Other names: Perjeta;Drug: Trastuzumab<br>* loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg for subsequent cycles<br>* Other names: Herceptin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Day 43 Serum Pertuzumab Trough Concentrations (Cmin) Greater Than or Equal to (>=) 20 Microgram Per Milliliter (mcg/mL) |  | Day 43 | 
| Number of Participants With Adverse Events (AEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment. | From randomization of first participant to end of study (approximately 6 years) |