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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01774786




Registration number
NCT01774786
Ethics application status
Date submitted
21/01/2013
Date registered
24/01/2013
Date last updated
30/12/2020

Titles & IDs
Public title
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
Scientific 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 and Gastric Cancer
Secondary ID [1] 0 0
2012-003554-83
Secondary ID [2] 0 0
BO25114
Universal Trial Number (UTN)
Trial acronym
JACOB
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastric Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 5-Fluorouracil
Treatment: Drugs - Capecitabine
Treatment: Drugs - Cisplatin
Treatment: Drugs - Pertuzumab
Treatment: Drugs - Placebo
Treatment: Drugs - Trastuzumab

Experimental: Pertuzumab + Trastuzumab + Chemotherapy - Participants 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). Thereafter, participants will continue to receive pertuzumab and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Placebo comparator: Placebo + Trastuzumab + Chemotherapy - Participants will receive placebo in combination with trastuzumab and chemotherapy (cisplatin and fluoropyrimidine \[capecitabine or 5-fluorouracil\]) for the first 6 treatment cycles (cycle length = 21 days). Thereafter, participants will continue to receive placebo and trastuzumab until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: Cisplatin
Participants will receive cisplatin 80 mg/m\^2 IV q3w for 6 cycles.

Treatment: Drugs: Pertuzumab
Participants will receive pertuzumab 840 mg IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Treatment: Drugs: Placebo
Participants will receive placebo (matched to pertuzumab) IV q3w until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
From Baseline until death from any cause (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.4 [0-42] months vs. 25.0 [0-41] months; Final Analysis: 46.1 [0-70] months vs. 44.4 [0-68] months)
Secondary outcome [1] 0 0
Progression-Free Survival, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria
Timepoint [1] 0 0
Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months)
Secondary outcome [2] 0 0
Primary Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria
Timepoint [2] 0 0
Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months)
Secondary outcome [3] 0 0
Final Analysis of the Percentage of Participants With Overall Objective Response, as Determined by the Investigator According to RECIST v1.1 Criteria
Timepoint [3] 0 0
Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Final Analysis: 50.4 [0-70] months vs. 47.4 [0-66] months)
Secondary outcome [4] 0 0
Duration of Objective Response, as Determined by Investigator According to RECIST v1.1 Criteria
Timepoint [4] 0 0
Baseline to death or progressive disease (PD), whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] vs. 21.3 [0-39] months; Final Analysis: 50.4 [0-70] vs. 47.4 [0-66] months)
Secondary outcome [5] 0 0
Percentage of Participants With Clinical Benefit, as Determined by the Investigator According to RECIST v1.1 Criteria
Timepoint [5] 0 0
Baseline up to death or progressive disease, whichever occurred first (Median [full range] duration of follow-up in Pertuzumab vs. Placebo arms for Primary Analysis: 24.9 [0-41] months vs. 21.3 [0-39] months)
Secondary outcome [6] 0 0
Overview of Safety: Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03
Timepoint [6] 0 0
From Baseline until end of post-treatment follow-up (up to 70 months)
Secondary outcome [7] 0 0
Number of Participants With Symptomatic or Asymptomatic Left Ventricular Systolic Dysfunction (LVSD)
Timepoint [7] 0 0
From Baseline until end of post-treatment follow-up (up to 70 months)
Secondary outcome [8] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score
Timepoint [8] 0 0
Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years)
Secondary outcome [9] 0 0
Change From Baseline in EORTC QLQ-Gastric Cancer Module (EORTC QLQ-STO22) Score
Timepoint [9] 0 0
Day 1 of each 21-day treatment cycle up to 28 and 60-90 days (post-treatment [PT] monitoring visits 1 and 2, respectively) after Day 1 of last treatment cycle (up to approximately 3.5 years)
Secondary outcome [10] 0 0
Maximum Serum Concentration (Cmax) of Pertuzumab
Timepoint [10] 0 0
Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days)
Secondary outcome [11] 0 0
Cmax of Trastuzumab
Timepoint [11] 0 0
Post-dose (0.5 hour after end of 30-60 minutes infusion) on Day 1 of Cycles 1, 2, 4, and 8 (1 cycle = 21 days)
Secondary outcome [12] 0 0
Minimum Serum Concentration (Cmin) of Pertuzumab
Timepoint [12] 0 0
Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)
Secondary outcome [13] 0 0
Cmin of Trastuzumab
Timepoint [13] 0 0
Pre-dose (0-6 hours before infusion) on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (1 cycle = 21 days)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/06/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/12/2019
Sample size
Target
Accrual to date
Final
780
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Royal Brisbane Womens Hosp; Division of Oncology - Herston
Recruitment hospital [2] 0 0
Monash Medical Centre; Oncology - Clayton
Recruitment hospital [3] 0 0
Austin Health; Cancer Clinical Trial Centre - Heidelberg
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital; Medical Oncology - Perth
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Nevada
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
South Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
Austria
State/province [9] 0 0
Salzburg
Country [10] 0 0
Austria
State/province [10] 0 0
Zams
Country [11] 0 0
Belgium
State/province [11] 0 0
Bruxelles
Country [12] 0 0
Brazil
State/province [12] 0 0
RJ
Country [13] 0 0
Brazil
State/province [13] 0 0
RS
Country [14] 0 0
Brazil
State/province [14] 0 0
SC
Country [15] 0 0
Brazil
State/province [15] 0 0
SP
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Plovdiv
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Sofia
Country [18] 0 0
Bulgaria
State/province [18] 0 0
Varna
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
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Canada
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Quebec
Country [21] 0 0
China
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Beijing
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China
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Changchun
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China
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Changzhou
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China
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ChongQing
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China
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Fuzhou
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China
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Guangzhou
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China
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Hangzhou
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China
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Harbin
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China
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Nanchang
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China
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Nanjing City
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China
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Nantong
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China
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Shanghai
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China
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Shenyang
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China
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Shijiazhuang
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China
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Xi'an
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China
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Xuzhou
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China
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Zhengzhou
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Croatia
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Zagreb
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El Salvador
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Salvador
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Finland
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Helsinki
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Finland
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Turku
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Germany
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Berlin
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Germany
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Essen
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Germany
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Esslingen
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Germany
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Hamburg
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Germany
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Leipzig
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Germany
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Ludwigsburg
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Germany
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Mainz
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Germany
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Mannheim
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Germany
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Marburg
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Germany
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Ulm
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Guatemala
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Guatemala
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Miskolc
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Hungary
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Szeged
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Italy
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Campania
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Italy
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Emilia-Romagna
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Italy
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Friuli-Venezia Giulia
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Italy
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Lazio
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Italy
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Lombardia
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Italy
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Marche
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Italy
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Puglia
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Toscana
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Aichi
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Chiba
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Ehime
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Japan
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Fukuoka
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Gifu
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Hiroshima
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Hyogo
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Kanagawa
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Osaka
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Saitama
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Tokyo
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Japan
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Toyama
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Kazakhstan
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Almaty
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Korea, Republic of
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Daegu
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Korea, Republic of
State/province [79] 0 0
Seoul
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Malaysia
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Kelantan
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Malaysia
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Kuala Lumpur
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Malaysia
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Sabah
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Mexico
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Mexico CITY (federal District)
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Mexico
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Mexico City
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Mexico
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Oaxaca
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Netherlands
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Amsterdam
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North Macedonia
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Bitola
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North Macedonia
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Skopje
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Panama
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Panama
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Peru
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Arequipa
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Peru
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Callao
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Peru
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Jesus Maria
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Peru
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Lima
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Poland
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Bialystok
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Brzozów
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Bydgoszcz
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Kraków
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Opole
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Poznan
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Poland
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Rybnik
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Poland
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Warszawa
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Romania
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Cluj-Napoca
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Romania
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Craiova
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Romania
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Iasi
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Russian Federation
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Kazan
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Russian Federation
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Omsk
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Russian Federation
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Ryazan
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Russian Federation
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Samara
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Spain
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Alicante
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Spain
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Barcelona
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Spain
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Cordoba
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Spain
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Madrid
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Switzerland
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Lausanne
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Switzerland
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Luzern
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei City
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Thailand
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Bangkok
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Thailand
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Khonkaen
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Thailand
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Songkhla
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Turkey
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Ankara
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Turkey
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Antalya
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Turkey
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Edirne
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Turkey
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Erzurum
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Turkey
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Istanbul
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Turkey
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Konya
Country [129] 0 0
Turkey
State/province [129] 0 0
Malatya

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01774786