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HELOISE: 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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Terminated
CT.gov ID
NCT01450696
Collaborator
(none)
296
Enrollment
117
Locations
2
Arms
44
Duration (Months)
2.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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/m2) 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/m2 on Day 1 of each 3-week cycle. Herceptin will be continued until disease progression occurs.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
296 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official 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
Study Start Date :
Dec 1, 2011
Actual Primary Completion Date :
Feb 1, 2015
Actual Study Completion Date :
Aug 1, 2015

Arms and Interventions

Arm Intervention/Treatment
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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Who Died - FAS [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.

    2. Overall Survival - FAS [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.

    Secondary Outcome Measures

    1. Percentage of Participants Who Died - Per Protocol Set (PPS) [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.

    2. Overall Survival - 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 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.

    3. Percentage of Participants With Disease Progression or Death - 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)]

      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.

    4. Progression-Free Survival - 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 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.

    5. Percentage of Participants With Objective Response - 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)]

      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.

    6. Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS [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.

    7. Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 La Jolla California United States 92093
    2 Los Angeles California United States 90033
    3 Whittier California United States 90603
    4 Whittier California United States 90606
    5 Goshen Indiana United States 46526
    6 Wichita Kansas United States 67214-3728
    7 New York New York United States 10065
    8 Portland Oregon United States 97239
    9 Charleston South Carolina United States 29425
    10 Port Macquarie New South Wales Australia 2444
    11 Wahroonga New South Wales Australia 2076
    12 Woodville South South Australia Australia 5011
    13 Murdoch Western Australia Australia 6150
    14 Banja Luka Bosnia and Herzegovina 78000
    15 Sarajewo Bosnia and Herzegovina 71000
    16 Rio de Janeiro RJ Brazil 20560-120
    17 Porto Alegre RS Brazil 90610-000
    18 Barretos SP Brazil 14784-400
    19 Sao Paulo SP Brazil 01246-000
    20 Sorocaba SP Brazil 18030-245
    21 Santiago Chile 7500921
    22 Santiago Chile 8380456
    23 Viña del Mar Chile 2520612
    24 Beijing China 100050
    25 Beijing China 100071
    26 Beijing China 100142
    27 Beijing China 100853
    28 Changchun China 130012
    29 Changsha China 410006
    30 Changzhou China 213003
    31 Guangzhou China 510060
    32 Hangzhou China 310016
    33 Nanjing China
    34 Shanghai China 200032
    35 Wuhan China 430030
    36 Zhengzhou China 450008
    37 Brno Czech Republic 656 53
    38 Olomouc Czech Republic 775 20
    39 Praha 2 Czech Republic 128 08
    40 Praha 8 Czech Republic 180 81
    41 Berlin Germany 10117
    42 Frankfurt Germany 60488
    43 Mannheim Germany 68167
    44 Budapest Hungary 1097
    45 Budapest Hungary 1145
    46 Pecs Hungary 7623
    47 Szolnok Hungary 5004
    48 Szombathely Hungary 9700
    49 Veszprem Hungary 8200
    50 Catanzaro Calabria Italy 88100
    51 Napoli Campania Italy 80131
    52 Bologna Emilia-Romagna Italy 40138
    53 Reggio Emilia Emilia-Romagna Italy 42100
    54 Udine Friuli-Venezia Giulia Italy 33100
    55 Milano Lombardia Italy 20133
    56 Ancona Marche Italy 60121
    57 Florence Toscana Italy 50124
    58 Pisa Toscana Italy 56100
    59 Bundang City Korea, Republic of 463-802
    60 Incheon Korea, Republic of 405-760
    61 Seoul Korea, Republic of 03722
    62 Seoul Korea, Republic of 06351
    63 Seoul Korea, Republic of 110-744
    64 Seoul Korea, Republic of 130-872
    65 Seoul Korea, Republic of 135-720
    66 Distrito Federal Mexico 14080
    67 Mexico City Mexico 06760
    68 Monterrey Mexico 64020
    69 Oaxaca Mexico 68000
    70 Auckland New Zealand 1023
    71 Panama Panama 0834-02723
    72 Arequipa Peru 04001
    73 Arequipa Peru 5154
    74 Lima Peru 1
    75 Lima Peru 34
    76 Lima Peru Lima 1
    77 Lima Peru Lima 41
    78 Trujillo Peru 13011
    79 Manila Philippines 1000
    80 Pasig City Philippines 1605
    81 Krakow Poland 31-501
    82 Lublin Poland 20-090
    83 Warsaw Poland 00-973
    84 Wieliszew Poland 05-135
    85 Porto Portugal 4200-072
    86 Ivanovo Russian Federation 153040
    87 Omsk Russian Federation 644013
    88 Ryazan Russian Federation 390011
    89 St Petersburg Russian Federation
    90 Stavropol Russian Federation 355045
    91 Tula Russian Federation 300053
    92 Belgrade Serbia 11000
    93 Nis Serbia 18000
    94 Sremska Kamenica Serbia 21204
    95 Bloemfontein South Africa 9300
    96 Cape Town South Africa 7506
    97 Johannesburg South Africa 2193
    98 Barcelona Spain 08035
    99 Barcelona Spain 08041
    100 Madrid Spain 28046
    101 Adana Turkey 01250
    102 Gaziantep Turkey 27100
    103 Istanbul Turkey 34890
    104 Izmir Turkey 35100
    105 Izmir Turkey 35340
    106 Malatya Turkey 44280
    107 Sıhhiye, ANKARA Turkey 06100
    108 Cherkassy Ukraine 18009
    109 Chernivtsi Ukraine 58013
    110 Dnipropetrovsk Ukraine 49102
    111 Donetsk Ukraine 83092
    112 Kiev Ukraine 03115
    113 Lvov Ukraine 79031
    114 Denbighshire United Kingdom LL185UJ
    115 Leicester United Kingdom LE1 5WW
    116 Southampton United Kingdom SO16 6YD
    117 Wolverhampton United Kingdom WV10 0QP

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT01450696
    Other Study ID Numbers:
    • BO27798
    • 2011-001526-19
    First Posted:
    Oct 12, 2011
    Last Update Posted:
    Nov 28, 2016
    Last Verified:
    Oct 1, 2016
    Additional relevant MeSH terms:
    Stomach Neoplasms
    Capecitabine
    Trastuzumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail A total of 248 participants (124 participants per arm) were randomized in the study up to data cutoff date of 13 February 2015, and 48 additional participants (24 participants per arm) were randomized between data cutoff date of 13 February 2015 and end of study (25 August 2015) for additional safety data.
    Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Arm/Group Description Participants received Herceptin at a loading dose of 8 milligrams per kilogram (mg/kg) on Day 1 of Cycle 1 followed by 6 mg/kg every three weeks (q3w) as 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 also received cisplatin 80 milligrams per meter-squared (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). Participants received 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 also received 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).
    Period Title: Overall Study
    STARTED 148 148
    Treated (Safety Population) 147 147
    COMPLETED 0 0
    NOT COMPLETED 148 148

    Baseline Characteristics

    Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg) Total
    Arm/Group Description Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as 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 also received 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). Participants received 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 also received 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). Total of all reporting groups
    Overall Participants 148 148 296
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    59.5
    (10.6)
    62.4
    (10.7)
    60.0
    (10.7)
    Sex: Female, Male (Count of Participants)
    Female
    32
    21.6%
    37
    25%
    69
    23.3%
    Male
    116
    78.4%
    111
    75%
    227
    76.7%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Who Died - FAS
    Description 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.
    Time Frame From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, number of participants analyzed reflects the number of participants who were evaluable for this outcome measure.
    Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Arm/Group Description Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as 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 also received 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). Participants received 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 also received 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).
    Measure Participants 124 124
    Number [percentage of participants]
    46.8
    31.6%
    54.0
    36.5%
    2. Primary Outcome
    Title Overall Survival - FAS
    Description 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.
    Time Frame From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, number of participants analyzed reflects the number of participants who were evaluable for this outcome measure.
    Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Arm/Group Description Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as 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 also received 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). Participants received 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 also received 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).
    Measure Participants 124 124
    Median (95% Confidence Interval) [months]
    12.485
    10.612
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Capecitabine + Cisplatin + Herceptin (6 mg/kg), Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Comments Stratified analysis included stratum of creatinine clearance (45 to 59 milliliters per minute [mL/min] and greater than or equal to [≥] 60 mL/min). Hazard ratio was estimated by Cox regression.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2401
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.24
    Confidence Interval (2-Sided) 95%
    0.86 to 1.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Capecitabine + Cisplatin + Herceptin (6 mg/kg), Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Comments Unstratified analysis. Hazard ratio was estimated by Cox regression.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1285
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.32
    Confidence Interval (2-Sided) 95%
    0.92 to 1.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Percentage of Participants Who Died - Per Protocol Set (PPS)
    Description The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the 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)

    Outcome Measure Data

    Analysis Population Description
    The PPS included all participants who were found to have a trastuzumab minimum plasma concentration (Cmin) less than (<) 12 micrograms per milliliter (μg/mL) on treatment Day 21 of Cycle 1 following the initial loading dose of 8 mg/kg.
    Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Arm/Group Description Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as 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 also received 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). Participants received 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 also received 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).
    Measure Participants 33 32
    Number [percentage of participants]
    51.5
    34.8%
    59.4
    40.1%
    4. Secondary Outcome
    Title Overall Survival - PPS
    Description 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.
    Time Frame From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)

    Outcome Measure Data

    Analysis Population Description
    PPS population.
    Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Arm/Group Description Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as 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 also received 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). Participants received 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 also received 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).
    Measure Participants 33 32
    Median (95% Confidence Interval) [months]
    10.809
    9.363
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Capecitabine + Cisplatin + Herceptin (6 mg/kg), Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Comments Stratified analysis included stratum of creatinine clearance (45 to 59 mL/min and ≥60 mL/min). Hazard ratio was estimated by Cox regression.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9931
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.00
    Confidence Interval (2-Sided) 95%
    0.49 to 2.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Capecitabine + Cisplatin + Herceptin (6 mg/kg), Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Comments Unstratified analysis. Hazard ratio was estimated by Cox regression.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.9458
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.02
    Confidence Interval (2-Sided) 95%
    0.52 to 2.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Percentage of Participants With Disease Progression or Death - PPS
    Description 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.
    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)

    Outcome Measure Data

    Analysis Population Description
    PPS population.
    Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Arm/Group Description Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as 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 also received 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). Participants received 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 also received 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).
    Measure Participants 33 32
    Number [percentage of participants]
    75.8
    51.2%
    81.3
    54.9%
    6. Secondary Outcome
    Title Progression-Free Survival - PPS
    Description 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.
    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)

    Outcome Measure Data

    Analysis Population Description
    PPS population.
    Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Arm/Group Description Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as 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 also received 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). Participants received 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 also received 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).
    Measure Participants 33 32
    Median (95% Confidence Interval) [months]
    5.388
    4.370
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Capecitabine + Cisplatin + Herceptin (6 mg/kg), Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Comments Stratified analysis included stratum of creatinine clearance (45 to 59 mL/min and ≥60 mL/min). Hazard ratio was estimated by Cox regression.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6759
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.13
    Confidence Interval (2-Sided) 95%
    0.63 to 2.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Capecitabine + Cisplatin + Herceptin (6 mg/kg), Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Comments Unstratified analysis. Hazard ratio was estimated by Cox regression.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5764
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.17
    Confidence Interval (2-Sided) 95%
    0.67 to 2.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Percentage of Participants With Objective Response - PPS
    Description 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.
    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)

    Outcome Measure Data

    Analysis Population Description
    PPS population.
    Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Arm/Group Description Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as 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 also received 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). Participants received 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 also received 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).
    Measure Participants 33 32
    Number (95% Confidence Interval) [percentage of participants]
    57.6
    38.9%
    50.0
    33.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Capecitabine + Cisplatin + Herceptin (6 mg/kg), Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Comments The 95% CI for difference in response rates was constructed using the normal approximation to the binomial distribution.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5402
    Comments
    Method Chi-squared
    Comments
    Method of Estimation Estimation Parameter Difference in response rates
    Estimated Value -7.58
    Confidence Interval (2-Sided) 95%
    -31.75 to 16.60
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Capecitabine + Cisplatin + Herceptin (6 mg/kg), Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.74
    Confidence Interval (2-Sided) 95%
    0.28 to 1.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS
    Description 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.
    Time Frame Day 21 of Cycle 1, 2, 3, 4, 5, 7, 9, 11 (cycle length = 21 days)

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, number of participants analyzed reflects the number of participants who were evaluable for this outcome measure. Here also, "n" reflects the number of participants who were evaluable for each category in the respective arms.
    Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Arm/Group Description Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as 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 also received 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). Participants received 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 also received 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).
    Measure Participants 100 99
    Cycle 1 (n=100,99)
    17.1
    (14.3)
    18.1
    (18.1)
    Cycle 2 (n=93,76)
    19.2
    (8.8)
    35.3
    (19.4)
    Cycle 3 (n=77,71)
    23.2
    (11.8)
    40.7
    (20.6)
    Cycle 4 (n=73,61)
    25.9
    (12.1)
    47.6
    (20.2)
    Cycle 5 (n=70,60)
    26.7
    (10.6)
    49.3
    (23.2)
    Cycle 7 (n=51,44)
    31.4
    (14.2)
    58.1
    (27.6)
    Cycle 9 (n=31,24)
    33.7
    (17.6)
    61.0
    (23.9)
    Cycle 11 (n=24,16)
    32.5
    (14.7)
    68.4
    (35.9)
    9. Secondary Outcome
    Title Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS
    Description 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.
    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)

    Outcome Measure Data

    Analysis Population Description
    FAS population. Here, number of participants analyzed reflects the number of participants who were evaluable for this outcome measure. Here also, "n" reflects the number of participants who were evaluable for each category in the respective arms.
    Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Arm/Group Description Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as 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 also received 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). Participants received 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 also received 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).
    Measure Participants 110 111
    Pre-dose (n=109,110)
    0.168
    (1.69)
    0.0204
    (0.123)
    End of infusion (n=110,111)
    126
    (59.6)
    137
    (55.7)

    Adverse Events

    Time Frame From date of randomization until 6 months after last dose of study drug or end of study (up to approximately 32 months or final data collection date of 25 August 2015)
    Adverse Event Reporting Description Safety evaluable population included all participants who were randomized and received at least one dose of any component of study treatment.
    Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Arm/Group Description Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as 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 also received 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). Participants received 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 also received 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).
    All Cause Mortality
    Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 35/147 (23.8%) 38/147 (25.9%)
    Blood and lymphatic system disorders
    Anemia 7/147 (4.8%) 6/147 (4.1%)
    Febrile neutropenia 3/147 (2%) 3/147 (2%)
    Neutropenia 1/147 (0.7%) 0/147 (0%)
    Pancytopenia 0/147 (0%) 1/147 (0.7%)
    Thrombocytopenia 0/147 (0%) 1/147 (0.7%)
    Cardiac disorders
    Bradycardia 1/147 (0.7%) 1/147 (0.7%)
    Cardiac arrest 1/147 (0.7%) 1/147 (0.7%)
    Cardiovascular insufficiency 1/147 (0.7%) 0/147 (0%)
    Myocardial infarction 0/147 (0%) 1/147 (0.7%)
    Palpitations 0/147 (0%) 1/147 (0.7%)
    Tachyarrhythmia 1/147 (0.7%) 0/147 (0%)
    Ventricular fibrillation 0/147 (0%) 1/147 (0.7%)
    Gastrointestinal disorders
    Abdominal pain upper 1/147 (0.7%) 0/147 (0%)
    Constipation 1/147 (0.7%) 0/147 (0%)
    Diarrhoea 0/147 (0%) 4/147 (2.7%)
    Gastric haemorrhage 2/147 (1.4%) 0/147 (0%)
    Gastrointestinal haemorrhage 1/147 (0.7%) 0/147 (0%)
    Intestinal obstruction 1/147 (0.7%) 0/147 (0%)
    Nausea 2/147 (1.4%) 0/147 (0%)
    Obstruction gastric 2/147 (1.4%) 1/147 (0.7%)
    Odynophagia 0/147 (0%) 1/147 (0.7%)
    Oesophageal haemorrhage 0/147 (0%) 1/147 (0.7%)
    Upper gastrointestinal haemorrhage 0/147 (0%) 1/147 (0.7%)
    Vomiting 5/147 (3.4%) 3/147 (2%)
    General disorders
    Asthenia 1/147 (0.7%) 0/147 (0%)
    Death 1/147 (0.7%) 1/147 (0.7%)
    Pyrexia 1/147 (0.7%) 0/147 (0%)
    Hepatobiliary disorders
    Drug-induced liver injury 0/147 (0%) 1/147 (0.7%)
    Infections and infestations
    Appendicitis 0/147 (0%) 1/147 (0.7%)
    Catheter site infection 0/147 (0%) 1/147 (0.7%)
    Cellulitis 0/147 (0%) 1/147 (0.7%)
    Infective spondylitis 0/147 (0%) 1/147 (0.7%)
    Neutropenic sepsis 0/147 (0%) 1/147 (0.7%)
    Pneumonia 2/147 (1.4%) 2/147 (1.4%)
    Sepsis 2/147 (1.4%) 1/147 (0.7%)
    Tinea pedis 0/147 (0%) 1/147 (0.7%)
    Tooth infection 1/147 (0.7%) 0/147 (0%)
    Urinary tract infection 1/147 (0.7%) 0/147 (0%)
    Injury, poisoning and procedural complications
    Infusion related reaction 0/147 (0%) 1/147 (0.7%)
    Lymphatic duct injury 1/147 (0.7%) 0/147 (0%)
    Spinal compression fracture 1/147 (0.7%) 0/147 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 2/147 (1.4%) 0/147 (0%)
    Diabetes mellitus 1/147 (0.7%) 1/147 (0.7%)
    Electrolyte imbalance 1/147 (0.7%) 0/147 (0%)
    Hypernatraemia 1/147 (0.7%) 0/147 (0%)
    Hypoalbuminaemia 0/147 (0%) 1/147 (0.7%)
    Hypocalcaemia 0/147 (0%) 1/147 (0.7%)
    Hypoglycaemia 0/147 (0%) 1/147 (0.7%)
    Hypokalaemia 2/147 (1.4%) 1/147 (0.7%)
    Hyponatraemia 0/147 (0%) 1/147 (0.7%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain 0/147 (0%) 1/147 (0.7%)
    Nervous system disorders
    Cerebral ischaemia 0/147 (0%) 1/147 (0.7%)
    Cerebrovascular accident 1/147 (0.7%) 0/147 (0%)
    Dizziness 0/147 (0%) 1/147 (0.7%)
    Haemorrhage intracranial 1/147 (0.7%) 0/147 (0%)
    Renal and urinary disorders
    Acute kidney injury 4/147 (2.7%) 2/147 (1.4%)
    Renal failure 3/147 (2%) 0/147 (0%)
    Ureteric obstruction 0/147 (0%) 1/147 (0.7%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/147 (0%) 1/147 (0.7%)
    Pneumonia aspiration 0/147 (0%) 1/147 (0.7%)
    Pulmonary embolism 1/147 (0.7%) 0/147 (0%)
    Vascular disorders
    Bleeding varicose vein 0/147 (0%) 1/147 (0.7%)
    Deep vein thrombosis 0/147 (0%) 1/147 (0.7%)
    Peripheral embolism 0/147 (0%) 1/147 (0.7%)
    Other (Not Including Serious) Adverse Events
    Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 123/147 (83.7%) 122/147 (83%)
    Blood and lymphatic system disorders
    Anaemia 47/147 (32%) 40/147 (27.2%)
    Leukopenia 26/147 (17.7%) 24/147 (16.3%)
    Neutropenia 61/147 (41.5%) 69/147 (46.9%)
    Thrombocytopenia 14/147 (9.5%) 14/147 (9.5%)
    Gastrointestinal disorders
    Abdominal pain 8/147 (5.4%) 7/147 (4.8%)
    Abdominal pain upper 12/147 (8.2%) 11/147 (7.5%)
    Constipation 19/147 (12.9%) 25/147 (17%)
    Diarrhoea 24/147 (16.3%) 30/147 (20.4%)
    Nausea 55/147 (37.4%) 55/147 (37.4%)
    Vomiting 36/147 (24.5%) 42/147 (28.6%)
    General disorders
    Asthenia 16/147 (10.9%) 11/147 (7.5%)
    Fatigue 25/147 (17%) 23/147 (15.6%)
    Oedema peripheral 9/147 (6.1%) 6/147 (4.1%)
    Pyrexia 15/147 (10.2%) 14/147 (9.5%)
    Investigations
    Weight decreased 10/147 (6.8%) 17/147 (11.6%)
    Metabolism and nutrition disorders
    Decreased appetite 32/147 (21.8%) 27/147 (18.4%)
    Hypoalbuminaemia 5/147 (3.4%) 10/147 (6.8%)
    Hypocalcaemia 9/147 (6.1%) 9/147 (6.1%)
    Hypokalaemia 6/147 (4.1%) 15/147 (10.2%)
    Hyponatraemia 3/147 (2%) 8/147 (5.4%)
    Nervous system disorders
    Dizziness 8/147 (5.4%) 2/147 (1.4%)
    Renal and urinary disorders
    Chronic kidney disease 7/147 (4.8%) 13/147 (8.8%)
    Renal failure 5/147 (3.4%) 8/147 (5.4%)
    Respiratory, thoracic and mediastinal disorders
    Cough 9/147 (6.1%) 3/147 (2%)
    Skin and subcutaneous tissue disorders
    Palmar-plantar erythrodysaesthesia syndrome 14/147 (9.5%) 20/147 (13.6%)

    Limitations/Caveats

    Trial was stopped for futility based on pre-planned interim analysis results.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

    Results Point of Contact

    Name/Title Medical Communications
    Organization Hoffmann-La Roche
    Phone 800-821-8590
    Email genentech@druginfo.com
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT01450696
    Other Study ID Numbers:
    • BO27798
    • 2011-001526-19
    First Posted:
    Oct 12, 2011
    Last Update Posted:
    Nov 28, 2016
    Last Verified:
    Oct 1, 2016