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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01450696




Trial ID
NCT01450696
Ethics application status
Date submitted
10/10/2011
Date registered
10/10/2011
Date last updated
5/10/2016

Titles & IDs
Public title
A Study of Herceptin (Trastuzumab) in Combination With Cisplatin/Capecitabine Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Gastric or Gastro-Esophageal Junction Cancer
Scientific title
A Randomized, Open Label, Multicenter Phase IIIb Study Comparing Two Trastuzumab Dosing Regimens, Each in Combination With Cisplatin/Capecitabine Chemotherapy, as First-Line Therapy in Patients With HER2-Positive Metastatic Gastric or Gastro-Esophageal Junction Adenocarcinoma Who Have Not Received Prior Treatment for Metastatic Disease
Secondary ID [1] 0 0
2011-001526-19
Secondary ID [2] 0 0
BO27798
Universal Trial Number (UTN)
Trial acronym
HELOISE
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 - Capecitabine
Treatment: Drugs - Cisplatin
Treatment: Drugs - Herceptin

Active Comparator: Capecitabine + Cisplatin + Herceptin (6 mg/kg) - Participants will receive Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as a standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants will also receive cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).

Experimental: Capecitabine + Cisplatin + Herceptin (10 mg/kg) - Participants will receive Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants will also receive cisplatin 80 mg/m^2 intravenously q3w plus capecitabine 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6).


Treatment: Drugs: Capecitabine
Capecitabine will be administered at a dose of 800 mg/m^2 orally twice daily for 14 days q3w for up to 6 cycles (Cycles 1 to 6).

Treatment: Drugs: Cisplatin
Cisplatin will be administered at a dose of 80 mg/m^2 intravenously q3w on Day 1 of each 3-week cycle for up to 6 cycles (Cycles 1 to 6).

Treatment: Drugs: Herceptin
Herceptin will be administered at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 or 10 mg/kg (depending upon treatment assignment) q3w from Day 1 of Cycle 2 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
Percentage of Participants Who Died - FAS - The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the FAS with available data.
Timepoint [1] 0 0
From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Primary outcome [2] 0 0
Overall Survival - FAS - Overall survival was defined as the time from the date of randomization to the date of death from any cause. Overall survival was estimated among participants from the FAS using the Kaplan-Meier approach. The 95 percent (%) confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley.
Timepoint [2] 0 0
From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Secondary outcome [1] 0 0
Percentage of Participants Who Died - Per Protocol Set (PPS) - The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the PPS.
Timepoint [1] 0 0
From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Secondary outcome [2] 0 0
Overall Survival - PPS - Overall survival was defined as the time from the date of randomization to the date of death from any cause. Overall survival was estimated among participants from the PPS using the Kaplan-Meier approach. The 95% CI for median was computed using the method of Brookmeyer and Crowley.
Timepoint [2] 0 0
From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Secondary outcome [3] 0 0
Percentage of Participants With Disease Progression or Death - PPS - Disease progression was defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as a =20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including Baseline (nadir). In addition to the relative increase of 20%, the sum was also required to demonstrate an absolute increase of =5 millimeters (mm). The percentage of participants who died or experienced disease progression as of the analysis data cutoff date of 13 February 2015 was reported among participants from the PPS.
Timepoint [3] 0 0
From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015)
Secondary outcome [4] 0 0
Progression-Free Survival - PPS - Progression-free survival was defined as the time between the day of randomization and the date of first documentation of disease progression or date of death, whichever occurred first, measured following RECIST Version 1.1 criteria. Disease progression was defined as a =20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including Baseline (nadir). In addition to the relative increase of 20%, the sum was also required to demonstrate an absolute increase of =5 mm. The 95% CI for median was computed using the method of Brookmeyer and Crowley.
Timepoint [4] 0 0
From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015)
Secondary outcome [5] 0 0
Percentage of Participants With Objective Response - PPS - Objective response was defined as the occurrence of either a complete response (CR) or partial response (PR) as determined by RECIST Version 1.1 based on investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) were required to have reduction in short axis to <10 mm. PR was defined as a =30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. The 95% CI was constructed using Blyth-Still-Casella method.
Timepoint [5] 0 0
From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015)
Secondary outcome [6] 0 0
Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS - Cmin samples were obtained in all participants randomized to receive Herceptin (FAS). The observed Cmin was recorded, averaged among all participants, and expressed in µg/mL.
Timepoint [6] 0 0
Day 21 of Cycle 1, 2, 3, 4, 5, 7, 9, 11 (cycle length = 21 days)
Secondary outcome [7] 0 0
Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS - Trastuzumab serum concentration samples were obtained in all participants randomized to receive Herceptin (FAS). The observed concentration values were recorded, averaged among all participants, and expressed in µg/mL.
Timepoint [7] 0 0
Pre-dose (0 minutes) and within 15 minutes after end of 2-hour Herceptin infusion on Day 1 of Cycle 1 (cycle length = 21 days)

Eligibility
Key inclusion criteria
- Histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction
with metastatic disease documented to involve at least liver or lung or both

- Measurable disease according to RECIST Version 1.1 or non-measurable evaluable disease

- At least 2 organs involved in metastatic gastric tumor (including at least lung or
liver or both) in addition to the site of primary tumor, where metastasis in distant
lymph nodes, peritoneal metastasis, and malignant pleural effusion may count as
"organs" in this context

- HER2-positive primary or metastatic tumor as assessed by central laboratory

- Adequate renal function (creatinine clearance greater than equal to (=) 45 milliliters
per minute [mL/min])

- Eastern Cooperative Oncology Group (ECOG) performance status of 2
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previous chemotherapy for locally advanced or metastatic disease

- Prior gastrectomy (partial or total) for the underlying malignant disease under
investigation

- Prior therapy with an anti-HER2 agent and/or platinum-based chemotherapeutic agent

- Residual relevant toxicity resulting from previous therapy

- Lack of physical integrity of the upper gastrointestinal tract or malabsorption
syndrome (such as jejunostomy probe and gastric or jejunostomy tubes) which may impair
the ability to administer or absorb capecitabine

- Current (significant or uncontrolled) gastrointestinal bleeding

- Other malignancy within the last 5 years, except for carcinoma in situ of the cervix
and basal or squamous cell carcinoma of the skin

- History of documented congestive heart failure, angina pectoris requiring medication,
electrocardiogram (ECG) evidence of transmural myocardial infraction, poorly
controlled hypertension, clinically significant valvular heart disease, or high-risk
uncontrollable arrhythmias

- Baseline left ventricular ejection fraction (LVEF) less than (<) 50%, documented by
echocardiography, multiple-gated radionuclide angiography (MUGA) scan, or cardiac
magnetic resonance imaging (MRI)

- Chronic or high-dose corticosteroid therapy

- History or clinical evidence of brain metastases

- Pregnant women

- Active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C,
or HIV-seropositive

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA
Recruitment hospital [1] 0 0
- Port Macquarie
Recruitment hospital [2] 0 0
- Wahroonga
Recruitment hospital [3] 0 0
- Woodville South
Recruitment hospital [4] 0 0
- Murdoch
Recruitment postcode(s) [1] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [2] 0 0
2076 - Wahroonga
Recruitment postcode(s) [3] 0 0
5011 - Woodville South
Recruitment postcode(s) [4] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Kansas
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Oregon
Country [6] 0 0
United States of America
State/province [6] 0 0
South Carolina
Country [7] 0 0
Bosnia and Herzegovina
State/province [7] 0 0
Banja Luka
Country [8] 0 0
Bosnia and Herzegovina
State/province [8] 0 0
Sarajewo
Country [9] 0 0
Brazil
State/province [9] 0 0
RJ
Country [10] 0 0
Brazil
State/province [10] 0 0
RS
Country [11] 0 0
Brazil
State/province [11] 0 0
SP
Country [12] 0 0
Chile
State/province [12] 0 0
Santiago
Country [13] 0 0
Chile
State/province [13] 0 0
Viña del Mar
Country [14] 0 0
China
State/province [14] 0 0
Beijing
Country [15] 0 0
China
State/province [15] 0 0
Changchun
Country [16] 0 0
China
State/province [16] 0 0
Changsha
Country [17] 0 0
China
State/province [17] 0 0
Changzhou
Country [18] 0 0
China
State/province [18] 0 0
Guangzhou
Country [19] 0 0
China
State/province [19] 0 0
Hangzhou
Country [20] 0 0
China
State/province [20] 0 0
Nanjing
Country [21] 0 0
China
State/province [21] 0 0
Shanghai
Country [22] 0 0
China
State/province [22] 0 0
Wuhan
Country [23] 0 0
China
State/province [23] 0 0
Zhengzhou
Country [24] 0 0
Czech Republic
State/province [24] 0 0
Brno
Country [25] 0 0
Czech Republic
State/province [25] 0 0
Olomouc
Country [26] 0 0
Czech Republic
State/province [26] 0 0
Praha 2
Country [27] 0 0
Czech Republic
State/province [27] 0 0
Praha 8
Country [28] 0 0
Germany
State/province [28] 0 0
Berlin
Country [29] 0 0
Germany
State/province [29] 0 0
Frankfurt
Country [30] 0 0
Germany
State/province [30] 0 0
Mannheim
Country [31] 0 0
Hungary
State/province [31] 0 0
Budapest
Country [32] 0 0
Hungary
State/province [32] 0 0
Pecs
Country [33] 0 0
Hungary
State/province [33] 0 0
Szolnok
Country [34] 0 0
Hungary
State/province [34] 0 0
Szombathely
Country [35] 0 0
Hungary
State/province [35] 0 0
Veszprem
Country [36] 0 0
Italy
State/province [36] 0 0
Calabria
Country [37] 0 0
Italy
State/province [37] 0 0
Campania
Country [38] 0 0
Italy
State/province [38] 0 0
Emilia-Romagna
Country [39] 0 0
Italy
State/province [39] 0 0
Friuli-Venezia Giulia
Country [40] 0 0
Italy
State/province [40] 0 0
Lombardia
Country [41] 0 0
Italy
State/province [41] 0 0
Marche
Country [42] 0 0
Italy
State/province [42] 0 0
Toscana
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Bundang City
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Incheon
Country [45] 0 0
Korea, Republic of
State/province [45] 0 0
Seoul
Country [46] 0 0
Mexico
State/province [46] 0 0
Distrito Federal
Country [47] 0 0
Mexico
State/province [47] 0 0
Mexico City
Country [48] 0 0
Mexico
State/province [48] 0 0
Monterrey
Country [49] 0 0
Mexico
State/province [49] 0 0
Oaxaca
Country [50] 0 0
New Zealand
State/province [50] 0 0
Auckland
Country [51] 0 0
Panama
State/province [51] 0 0
Panama
Country [52] 0 0
Peru
State/province [52] 0 0
Arequipa
Country [53] 0 0
Peru
State/province [53] 0 0
Lima
Country [54] 0 0
Peru
State/province [54] 0 0
Trujillo
Country [55] 0 0
Philippines
State/province [55] 0 0
Manila
Country [56] 0 0
Philippines
State/province [56] 0 0
Pasig City
Country [57] 0 0
Poland
State/province [57] 0 0
Krakow
Country [58] 0 0
Poland
State/province [58] 0 0
Lublin
Country [59] 0 0
Poland
State/province [59] 0 0
Warsaw
Country [60] 0 0
Poland
State/province [60] 0 0
Wieliszew
Country [61] 0 0
Portugal
State/province [61] 0 0
Porto
Country [62] 0 0
Russian Federation
State/province [62] 0 0
Ivanovo
Country [63] 0 0
Russian Federation
State/province [63] 0 0
Omsk
Country [64] 0 0
Russian Federation
State/province [64] 0 0
Ryazan
Country [65] 0 0
Russian Federation
State/province [65] 0 0
St Petersburg
Country [66] 0 0
Russian Federation
State/province [66] 0 0
Stavropol
Country [67] 0 0
Russian Federation
State/province [67] 0 0
Tula
Country [68] 0 0
Serbia
State/province [68] 0 0
Belgrade
Country [69] 0 0
Serbia
State/province [69] 0 0
Nis
Country [70] 0 0
Serbia
State/province [70] 0 0
Sremska Kamenica
Country [71] 0 0
South Africa
State/province [71] 0 0
Bloemfontein
Country [72] 0 0
South Africa
State/province [72] 0 0
Cape Town
Country [73] 0 0
South Africa
State/province [73] 0 0
Johannesburg
Country [74] 0 0
Spain
State/province [74] 0 0
Barcelona
Country [75] 0 0
Spain
State/province [75] 0 0
Madrid
Country [76] 0 0
Turkey
State/province [76] 0 0
Adana
Country [77] 0 0
Turkey
State/province [77] 0 0
Gaziantep
Country [78] 0 0
Turkey
State/province [78] 0 0
Istanbul
Country [79] 0 0
Turkey
State/province [79] 0 0
Izmir
Country [80] 0 0
Turkey
State/province [80] 0 0
Malatya
Country [81] 0 0
Turkey
State/province [81] 0 0
Sihhiye, ANKARA
Country [82] 0 0
Ukraine
State/province [82] 0 0
Cherkassy
Country [83] 0 0
Ukraine
State/province [83] 0 0
Chernivtsi
Country [84] 0 0
Ukraine
State/province [84] 0 0
Dnipropetrovsk
Country [85] 0 0
Ukraine
State/province [85] 0 0
Donetsk
Country [86] 0 0
Ukraine
State/province [86] 0 0
Kiev
Country [87] 0 0
Ukraine
State/province [87] 0 0
Lvov
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Denbighshire
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Leicester
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Southampton
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Wolverhampton

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

Ethics approval
Ethics application status

Summary
Brief summary
This randomized, open-label, multicenter, international Phase IIIb study will compare the
efficacy and safety of two Herceptin dosing regimens in combination with
cisplatin/capecitabine chemotherapy in participants with HER2-positive metastatic gastric or
gastro-esophageal junction adenocarcinoma. Participants who have not received prior treatment
for metastatic disease will be randomized to receive Herceptin intravenously as either an
8-milligram per kilogram (mg/kg) loading dose followed by 6 mg/kg every 3 weeks (q3w) as
standard of care or an 8-mg/kg loading dose followed by 10 mg/kg q3w until disease
progression. Capecitabine will be administered for 6 cycles at a dose of 800 milligrams per
meter-squared (mg/m^2) orally twice a day on Days 1 to 14 of each 3-week cycle, and cisplatin
will be administered intravenously for 6 cycles at a dose of 80 mg/m^2 on Day 1 of each
3-week cycle. Herceptin will be continued until disease progression occurs.
Trial website
https://clinicaltrials.gov/show/NCT01450696
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