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 (HELOISE)

October 5, 2016 updated by: Hoffmann-La Roche

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
296

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Port Macquarie, New South Wales, Australia, 2444
      • Wahroonga, New South Wales, Australia, 2076
    • South Australia
      • Woodville South, South Australia, Australia, 5011
    • Western Australia
      • Murdoch, Western Australia, Australia, 6150
  • Bosnia and Herzegovina
      • Banja Luka, Bosnia and Herzegovina, 78000
      • Sarajewo, Bosnia and Herzegovina, 71000
  • Brazil
    • RJ
      • Rio de Janeiro, RJ, Brazil, 20560-120
    • RS
      • Porto Alegre, RS, Brazil, 90610-000
    • SP
      • Barretos, SP, Brazil, 14784-400
      • Sao Paulo, SP, Brazil, 01246-000
      • Sorocaba, SP, Brazil, 18030-245
  • Chile
      • Santiago, Chile, 7500921
      • Santiago, Chile, 8380456
      • Viña del Mar, Chile, 2520612
  • China
      • Beijing, China, 100050
      • Beijing, China, 100142
      • Beijing, China, 100071
      • Beijing, China, 100853
      • Changchun, China, 130012
      • Changsha, China, 410006
      • Changzhou, China, 213003
      • Guangzhou, China, 510060
      • Hangzhou, China, 310016
      • Nanjing, China
      • Shanghai, China, 200032
      • Wuhan, China, 430030
      • Zhengzhou, China, 450008
  • Czech Republic
      • Brno, Czech Republic, 656 53
      • Olomouc, Czech Republic, 775 20
      • Praha 2, Czech Republic, 128 08
      • Praha 8, Czech Republic, 180 81
  • Germany
      • Berlin, Germany, 10117
      • Frankfurt, Germany, 60488
      • Mannheim, Germany, 68167
  • Hungary
      • Budapest, Hungary, 1145
      • Budapest, Hungary, 1097
      • Pecs, Hungary, 7623
      • Szolnok, Hungary, 5004
      • Szombathely, Hungary, 9700
      • Veszprem, Hungary, 8200
  • Italy
    • Calabria
      • Catanzaro, Calabria, Italy, 88100
    • Campania
      • Napoli, Campania, Italy, 80131
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40138
      • Reggio Emilia, Emilia-Romagna, Italy, 42100
    • Friuli-Venezia Giulia
      • Udine, Friuli-Venezia Giulia, Italy, 33100
    • Lombardia
      • Milano, Lombardia, Italy, 20133
    • Marche
      • Ancona, Marche, Italy, 60121
    • Toscana
      • Florence, Toscana, Italy, 50124
      • Pisa, Toscana, Italy, 56100
  • Korea, Republic of
      • Bundang City, Korea, Republic of, 463-802
      • Incheon, Korea, Republic of, 405-760
      • Seoul, Korea, Republic of, 110-744
      • Seoul, Korea, Republic of, 135-720
      • Seoul, Korea, Republic of, 06351
      • Seoul, Korea, Republic of, 130-872
      • Seoul, Korea, Republic of, 03722
  • Mexico
      • Distrito Federal, Mexico, 14080
      • Mexico City, Mexico, 06760
      • Monterrey, Mexico, 64020
      • Oaxaca, Mexico, 68000
  • New Zealand
      • Auckland, New Zealand, 1023
  • Panama
      • Panama, Panama, 0834-02723
  • Peru
      • Arequipa, Peru, 04001
      • Arequipa, Peru, 5154
      • Lima, Peru, 34
      • Lima, Peru, Lima 1
      • Lima, Peru, Lima 41
      • Lima, Peru, 1
      • Trujillo, Peru, 13011
  • Philippines
      • Manila, Philippines, 1000
      • Pasig City, Philippines, 1605
  • Poland
      • Krakow, Poland, 31-501
      • Lublin, Poland, 20-090
      • Warsaw, Poland, 00-973
      • Wieliszew, Poland, 05-135
  • Portugal
      • Porto, Portugal, 4200-072
  • Russian Federation
      • Ivanovo, Russian Federation, 153040
      • Omsk, Russian Federation, 644013
      • Ryazan, Russian Federation, 390011
      • St Petersburg, Russian Federation
      • Stavropol, Russian Federation, 355045
      • Tula, Russian Federation, 300053
  • Serbia
      • Belgrade, Serbia, 11000
      • Nis, Serbia, 18000
      • Sremska Kamenica, Serbia, 21204
  • South Africa
      • Bloemfontein, South Africa, 9300
      • Cape Town, South Africa, 7506
      • Johannesburg, South Africa, 2193
  • Spain
      • Barcelona, Spain, 08035
      • Barcelona, Spain, 08041
      • Madrid, Spain, 28046
  • Turkey
      • Adana, Turkey, 01250
      • Gaziantep, Turkey, 27100
      • Istanbul, Turkey, 34890
      • Izmir, Turkey, 35100
      • Izmir, Turkey, 35340
      • Malatya, Turkey, 44280
      • Sıhhiye, ANKARA, Turkey, 06100
  • Ukraine
      • Cherkassy, Ukraine, 18009
      • Chernivtsi, Ukraine, 58013
      • Dnipropetrovsk, Ukraine, 49102
      • Donetsk, Ukraine, 83092
      • Kiev, Ukraine, 03115
      • Lvov, Ukraine, 79031
  • United Kingdom
      • Denbighshire, United Kingdom, LL185UJ
      • Leicester, United Kingdom, LE1 5WW
      • Southampton, United Kingdom, SO16 6YD
      • Wolverhampton, United Kingdom, WV10 0QP
  • United States
    • California
      • La Jolla, California, United States, 92093
      • Los Angeles, California, United States, 90033
      • Whittier, California, United States, 90603
      • Whittier, California, United States, 90606
    • Indiana
      • Goshen, Indiana, United States, 46526
    • Kansas
      • Wichita, Kansas, United States, 67214-3728
    • New York
      • New York, New York, United States, 10065
    • Oregon
      • Portland, Oregon, United States, 97239
    • South Carolina
      • Charleston, South Carolina, United States, 29425

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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).
Drug: 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).
Drug: 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).
Drug: 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.
Other Names:
  • Trastuzumab
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).
Drug: 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).
Drug: 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).
Drug: 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.
Other Names:
  • Trastuzumab

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Died - FAS
Time Frame: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
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.
From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Overall Survival - FAS
Time Frame: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
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.
From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Died - Per Protocol Set (PPS)
Time Frame: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the PPS.
From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Overall Survival - PPS
Time Frame: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
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.
From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Percentage of Participants With Disease Progression or Death - PPS
Time Frame: 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)
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.
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)
Progression-Free Survival - PPS
Time Frame: 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)
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.
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)
Percentage of Participants With Objective Response - PPS
Time Frame: 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)
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.
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)
Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS
Time Frame: Day 21 of Cycle 1, 2, 3, 4, 5, 7, 9, 11 (cycle length = 21 days)
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.
Day 21 of Cycle 1, 2, 3, 4, 5, 7, 9, 11 (cycle length = 21 days)
Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS
Time Frame: 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)
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.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2011

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2015

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 10, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 10, 2011

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 28, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 5, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BO27798
  • 2011-001526-19 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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