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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

  Hide Study Locations
Locations
United States, California
Stanford, California, United States, 94305-5820
United States, Colorado
Denver, Colorado, United States, 80218
United States, Florida
Fort Myers, Florida, United States, 33916
Orlando, Florida, United States, 32804
St.Petersburg, Florida, United States, 33705
United States, Illinois
Chicago, Illinois, United States, 60637
United States, Indiana
Goshen, Indiana, United States, 46526
United States, Minnesota
Minneapolis, Minnesota, United States, 55407
United States, Nevada
Las Vegas, Nevada, United States, 89169
United States, New York
Albany, New York, United States, 12206
Fresh Meadows, New York, United States, 11366
New York, New York, United States, 10065
United States, Ohio
Cincinnati, Ohio, United States, 45219
United States, South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Nashville, Tennessee, United States, 37203
United States, Texas
Lewisville, Texas, United States, 75067
Paris, Texas, United States, 75460
Tyler, Texas, United States, 75702
United States, Virginia
Fairfax, Virginia, United States, 22031
United States, Washington
Edmonds, Washington, United States, 98026
Tacoma, Washington, United States, 98405
Australia, Queensland
Herston, Queensland, Australia, 4029
Australia, Victoria
East Bentleigh, Victoria, Australia, VIC 3165
Heidelberg, Victoria, Australia, 3084
Australia, Western Australia
Perth, Western Australia, Australia, 6009
Austria
Salzburg, Austria, 5020
Zams, Austria, 6511
Belgium
Bruxelles, Belgium, 1200
Brazil
Rio De Janeiro, RJ, Brazil, 22290-160
Porto Alegre, RS, Brazil, 90035-003
Porto Alegre, RS, Brazil, 91350-200
Florianopolis, SC, Brazil, 88034-000
Sao Paulo, SP, Brazil, 01308-050
Sao Paulo, SP, Brazil, 01406100
Sao Paulo, SP, Brazil, 01509-010
Sao Paulo, SP, Brazil, 22793-080
Bulgaria
Plovdiv, Bulgaria, 4004
Sofia, Bulgaria, 1301
Sofia, Bulgaria, 1606
Varna, Bulgaria, 9010
Canada, Newfoundland and Labrador
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Ontario
Hamilton, Ontario, Canada, L8V 5C2
London, Ontario, Canada, N6A 4L6
Sudbury, Ontario, Canada, P3E 5J1
Toronto, Ontario, Canada, M4C 3E7
Toronto, Ontario, Canada, M4N 3M5
Toronto, Ontario, Canada, M5G 1X5
Canada, Quebec
Montreal, Quebec, Canada, H4A 3J1
China
Beijing, China, 100021
Beijing, China, 100071
Beijing, China, 100142
Changchun, China, 130012
Changchun, China, 130021
Changzhou, China, 213003
ChongQing, China, 400042
Fuzhou, China, 110016
Fuzhou, China, 350014
Guangzhou, China, 510060
Hangzhou, China, 310016
Harbin, China, 150081
Nanchang, China, 330006
Nanjing, China
Nantong, China, 226001
Shanghai, China, 200032
Shenyang, China, 110016
Shijiazhuang, China, 050035
Xi'an, China, 710032
Xuzhou, China, 221004
Zhengzhou, China, 450008
Zhengzhou, China, 450052
Croatia
Osijek, Croatia, 31000
Zagreb, Croatia, 10000
El Salvador
Salvador, El Salvador, 01101
Finland
Helsinki, Finland, 00180
Turku, Finland, 20520
Germany
Berlin, Germany, 10117
Essen, Germany, 45122
Essen, Germany, 45136
Esslingen, Germany, 73730
Hamburg, Germany, 20246
Leipzig, Germany, 04103
Ludwigsburg, Germany, 71640
Mainz, Germany, 55131
Mannheim, Germany, 68167
Marburg, Germany, 35043
Ulm, Germany, 89081
Guatemala
Guatemala, Guatemala, 01-010
Hungary
Budapest, Hungary, 1083
Budapest, Hungary, 1122
Debrecen, Hungary, 4032
Miskolc, Hungary, 3526
Szeged, Hungary, 6720
Italy
Catanzaro, Calabria, Italy, 88100
Napoli, Campania, Italy, 80131
Bologna, Emilia-Romagna, Italy, 40138
Reggio Emilia, Emilia-Romagna, Italy, 42100
Udine, Friuli-Venezia Giulia, Italy, 33100
Roma, Lazio, Italy, 00168
Genova, Liguria, Italy, 16132
Bergamo, Lombardia, Italy, 24128
Milano, Lombardia, Italy, 20132
Milano, Lombardia, Italy, 20141
Ancona, Marche, Italy, 60121
San Giovanni Rotondo, Puglia, Italy, 71013
Pisa, Toscana, Italy, 56100
Prato, Toscana, Italy, 59100
Japan
Aichi, Japan, 464-8681
Aichi, Japan, 466-8560
Chiba, Japan, 277-8577
Ehime, Japan, 791-0280
Fukuoka, Japan, 812-8582
Gifu, Japan, 501-1194
Hiroshima, Japan, 730-8518
Hyogo, Japan, 650-0047
Kanagawa, Japan, 216-8511
Kanagawa, Japan, 241-8515
Osaka, Japan, 537-8511
Osaka, Japan, 558-8558
Saitama, Japan, 362-0806
Tokyo, Japan, 104-0045
Toyama, Japan, 930-0194
Kazakhstan
Almaty, Kazakhstan, 050022
Almaty, Kazakhstan, 050060
Korea, Republic of
Daegu, Korea, Republic of, 41404
Seoul, Korea, Republic of, 03080
Seoul, Korea, Republic of, 03722
Seoul, Korea, Republic of, 05505
Seoul, Korea, Republic of, 06351
Seoul, Korea, Republic of, 06591
Macedonia, The Former Yugoslav Republic of
Bitola, Macedonia, The Former Yugoslav Republic of, 7000
Skopje, Macedonia, The Former Yugoslav Republic of, 1000
Malaysia
Kota Bharu Kelantan, Malaysia, 16150
Kuala Lumpur, Malaysia, 50586
Kuala Lumpur, Malaysia, 59100
Sabah, Malaysia, 88996
Mexico
Mexico City, Mexico, 06760
Mexico City, Mexico, 14000
Oaxaca, Mexico, 68000
Netherlands
Amsterdam, Netherlands, 1105 AZ
Panama
Panama, Panama
Peru
Arequipa, Peru, 04001
Callao, Peru, 02
Jesus Maria, Peru, Lima 11
Lima, Peru, Lima 41
Miraflores, Peru, Lima 18
Poland
Bialystok, Poland, 15-027
Brzozów, Poland, 36-200
Bydgoszcz, Poland, 85-796
Krakow, Poland, 31-531
Opole, Poland, 45-060
Poznan, Poland, 61-485
Rybnik, Poland, 44-200
Warszawa, Poland, 02-781
Wroclaw, Poland, 53-439
Romania
Bucharest, Romania, 022328
Cluj-Napoca, Romania, 400015
Craiova, Romania, 200347
Iasi, Romania, 700106
Russian Federation
Kazan, Russian Federation, 420029
Omsk, Russian Federation, 644013
Rostov-on-Don, Russian Federation, 344037
Ryazan, Russian Federation, 390011
Samara, Russian Federation, 443031
Spain
Elche, Alicante, Spain, 03203
Barcelona, Spain, 08003
Barcelona, Spain, 08035
Barcelona, Spain, 08041
Barcelona, Spain, 08907
Barcelona, Spain, 08916
Cordoba, Spain, 14004
Madrid, Spain, 28034
Madrid, Spain, 28041
Switzerland
Lausanne, Switzerland, 1011
Luzern, Switzerland, 6004
Zürich, Switzerland, 8063
Taiwan
Taichung, Taiwan, 407
Tainan, Taiwan, 00704
Taipei, Taiwan, 00112
Taipei, Taiwan, 100
Taoyuan, Taiwan, 333
Thailand
Bangkok, Thailand, 10400
Bangkok, Thailand, 10700
Khonkaen, Thailand, 40000
Patumwan, Thailand, 10330
Songkhla, Thailand, 90110
Turkey
Ankara, Turkey, 06590
Antalya, Turkey, 07070
Edirne, Turkey, 22770
Erzurum, Turkey, 25240
Istanbul, Turkey, 34300
Konya, Turkey, 42080
Malatya, Turkey, 44280
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 02, 2016