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

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

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Capecitabine; Drug: Cisplatin; Drug: Pertuzumab; Drug: Pertuzumab; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• Czechia
  • Brno, Czechia, 656 53
    • Masaryk Memorial Cancer Institute; Oncological Clinic
  • Hradec Kralove, Czechia, 500 05
    • Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc; Onkologicka klinika
  • Praha 5, Czechia, 150 06
    • Fakultní Nemocnice V Motole; Radioterapeuticko-Onkologicke Oddeleni
  • Praha 8, Czechia, 180 81
    • University Hospital Na Bulovce; Institut of Radiation Oncology
• France
  • Brest, France, 29200
    • Hopital Morvan
  • Montpellier cedex 5, France, 34298
    • CRLCC Val dAurelle Paul Lam
  • Reims, France, 51092
    • Hopital Robert Debre; DERMATOLOGIE
• Germany
  • Berlin, Germany, 10117
    • Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.
  • Braunschweig, Germany, 38114
    • Klinikum Braunschweig; Medizinische Klinik III; Klinik für Hämatologie und Onkologie
  • Frankfurt, Germany, 60488
    • Krankenhaus Nordwest; Klinik f. Onkologie und Hämatologie
  • Mannheim, Germany, 68167
    • Klinikum Mannheim III. Medizinische Klinik
• Italy
  • Calabria
    • Catanzaro, Calabria, Italy, 88100
      • Campus Universitario S.Venuta; Centro Oncologico T.Campanella
  • Lombardia
    • Milano, Lombardia, Italy, 20133
      • Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
  • Toscana
    • Pisa, Toscana, Italy, 56100
      • A.O. Universitaria Pisana; Oncologia
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center; Medical Oncology
  • Seoul, Korea, Republic of, 03722
    • Yonsei Medical Center; Dept. of Medicine , Division of Hemato-Oncology
• Netherlands
  • Maastricht, Netherlands, 6229 HX
    • Academish Ziekenhuis Maastricht (Azm); Inwendige Geneeskunde
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar; Servicio de Oncologia
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz; Servicio de Oncologia
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pertuzumab 840/420 mg; 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; 1000 mg/m2 twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle; Other Names: Xeloda; Drug: Cisplatin; 80 mg/m2 on Day 1 of each cycle; Drug: Pertuzumab; loading dose of 840 mg, then 420 mg once every three weeks; Other Names: Perjeta; Drug: Pertuzumab; 840 mg once every three weeks; Other Names: Perjeta; Drug: Trastuzumab; loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg for subsequent cycles; Other Names: Herceptin
Experimental: Pertuzumab 840/840 mg; 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; 1000 mg/m2 twice daily, from the evening of Day 1 to the morning of Day 15 of each cycle; Other Names: Xeloda; Drug: Cisplatin; 80 mg/m2 on Day 1 of each cycle; Drug: Pertuzumab; loading dose of 840 mg, then 420 mg once every three weeks; Other Names: Perjeta; Drug: Pertuzumab; 840 mg once every three weeks; Other Names: Perjeta; Drug: Trastuzumab; loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg for subsequent cycles; 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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2011
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): October 31, 2017

Study Registration Dates

• First Submitted: October 26, 2011
• First Submitted That Met QC Criteria: October 26, 2011
• First Posted (Estimate): October 27, 2011

Study Record Updates

• Last Update Posted (Actual): August 9, 2018
• Last Update Submitted That Met QC Criteria: July 13, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab; Capecitabine; Pertuzumab
• Other Study ID Numbers: BP27836