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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)

This study has been terminated.
(futility following planned interim analysis)
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01450696
First received: October 10, 2011
Last updated: October 5, 2016
Last verified: October 2016

October 10, 2011
October 5, 2016
December 2011
February 2015   (final data collection date for primary outcome measure)
  • 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) ] [ Designated as safety issue: No ]
    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.
  • 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) ] [ Designated as safety issue: No ]
    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.
Overall survival [ Time Frame: approximately 8 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01450696 on ClinicalTrials.gov Archive Site
  • 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) ] [ Designated as safety issue: No ]
    The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the PPS.
  • 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) ] [ Designated as safety issue: No ]
    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.
  • 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) ] [ Designated as safety issue: No ]
    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.
  • 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) ] [ Designated as safety issue: No ]
    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.
  • 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) ] [ Designated as safety issue: No ]
    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.
  • 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) ] [ Designated as safety issue: No ]
    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.
  • 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) ] [ Designated as safety issue: No ]
    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.
  • Duration of overall survival in patients with trastuzumab minimum concentrations Cmin <12 mcg/mL on Day 21 of Cycle 1 [ Time Frame: approximately 8 years ] [ Designated as safety issue: No ]
  • Trastuzumab minimum concentrations (Cmin) on Day 21 of Cycles 1-11 [ Time Frame: 33 weeks ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: approximately 8 years ] [ Designated as safety issue: No ]
  • Progression-free survival in patients with trastuzumab Cmin <12 mcg/mL on Day 21 of Cycle 1 [ Time Frame: approximately 8 years ] [ Designated as safety issue: No ]
  • Objective response rate in patients with trastuzumab Cmin <12 mcg/mL on Day 21 of Cycle 1 [ Time Frame: approximately 8 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Gastric Cancer
  • 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 Name: Trastuzumab
  • 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).
    Interventions:
    • Drug: Capecitabine
    • Drug: Cisplatin
    • Drug: Herceptin
  • 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).
    Interventions:
    • Drug: Capecitabine
    • Drug: Cisplatin
    • Drug: Herceptin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
296
August 2015
February 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Bosnia and Herzegovina,   Brazil,   Chile,   China,   Czech Republic,   Germany,   Hungary,   Italy,   Korea, Republic of,   Mexico,   New Zealand,   Panama,   Peru,   Philippines,   Poland,   Portugal,   Russian Federation,   Serbia,   South Africa,   Spain,   Turkey,   Ukraine,   United Kingdom
Costa Rica,   India,   Romania
 
NCT01450696
BO27798, 2011-001526-19
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP