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Trial record 58 of 193 for:    Oral Cancer | ( Map: Mexico )

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)

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ClinicalTrials.gov Identifier: NCT01450696
Recruitment Status : Terminated (futility following planned interim analysis)
First Posted : October 12, 2011
Results First Posted : November 28, 2016
Last Update Posted : November 28, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Gastric Cancer
Interventions Drug: Capecitabine
Drug: Cisplatin
Drug: Herceptin
Enrollment 296
Recruitment Details  
Pre-assignment Details 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)
Hide 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
Reason Not Completed
Never Treated             1             1
Death             77             84
Lost to Follow-up             3             3
Non-Compliance             1             0
Withdrawal by Subject             13             2
Study Terminated by Sponsor             53             58
Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg) Total
Hide 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 Number of Baseline Participants 148 148 296
Hide Baseline Analysis Population Description
The Full Analysis Set (FAS) population included all participants who were randomized in this study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 148 participants 148 participants 296 participants
59.5  (10.6) 62.4  (10.7) 60.0  (10.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 148 participants 148 participants 296 participants
Female
32
  21.6%
37
  25.0%
69
  23.3%
Male
116
  78.4%
111
  75.0%
227
  76.7%
1.Primary Outcome
Title Percentage of Participants Who Died - FAS
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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).
Overall Number of Participants Analyzed 124 124
Measure Type: Number
Unit of Measure: percentage of participants
46.8 54.0
2.Primary Outcome
Title Overall Survival - FAS
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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).
Overall Number of Participants Analyzed 124 124
Median (95% Confidence Interval)
Unit of Measure: months
12.485
(10.086 to 13.864)
10.612
(9.363 to 12.419)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.2401
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.24
Confidence Interval (2-Sided) 95%
0.86 to 1.78
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.1285
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.32
Confidence Interval (2-Sided) 95%
0.92 to 1.88
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Who Died - Per Protocol Set (PPS)
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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).
Overall Number of Participants Analyzed 33 32
Measure Type: Number
Unit of Measure: percentage of participants
51.5 59.4
4.Secondary Outcome
Title Overall Survival - PPS
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
PPS population.
Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
Hide 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).
Overall Number of Participants Analyzed 33 32
Median (95% Confidence Interval)
Unit of Measure: months
10.809
(8.082 to 14.752)
9.363
(5.552 to 14.357)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.9931
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.49 to 2.04
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.9458
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.52 to 2.02
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Disease Progression or Death - PPS
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
PPS population.
Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
Hide 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).
Overall Number of Participants Analyzed 33 32
Measure Type: Number
Unit of Measure: percentage of participants
75.8 81.3
6.Secondary Outcome
Title Progression-Free Survival - PPS
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
PPS population.
Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
Hide 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).
Overall Number of Participants Analyzed 33 32
Median (95% Confidence Interval)
Unit of Measure: months
5.388
(2.793 to 7.721)
4.370
(2.727 to 6.834)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.6759
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.63 to 2.02
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.5764
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.67 to 2.05
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With Objective Response - PPS
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
PPS population.
Arm/Group Title Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
Hide 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).
Overall Number of Participants Analyzed 33 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
57.6
(40.12 to 73.16)
50.0
(31.89 to 68.11)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.5402
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value -7.58
Confidence Interval (2-Sided) 95%
-31.75 to 16.60
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Capecitabine + Cisplatin + Herceptin (6 mg/kg), Capecitabine + Cisplatin + Herceptin (10 mg/kg)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.28 to 1.96
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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).
Overall Number of Participants Analyzed 100 99
Mean (Standard Deviation)
Unit of Measure: μg/mL
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
Hide 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)
Hide Outcome Measure Data
Hide 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)
Hide 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).
Overall Number of Participants Analyzed 110 111
Mean (Standard Deviation)
Unit of Measure: μg/mL
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)
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)
Hide 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 (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
Affected / at Risk (%) Affected / at Risk (%)
Total   35/147 (23.81%)   38/147 (25.85%) 
Blood and lymphatic system disorders     
Anemia * 1  7/147 (4.76%)  6/147 (4.08%) 
Febrile neutropenia * 1  3/147 (2.04%)  3/147 (2.04%) 
Neutropenia * 1  1/147 (0.68%)  0/147 (0.00%) 
Pancytopenia * 1  0/147 (0.00%)  1/147 (0.68%) 
Thrombocytopenia * 1  0/147 (0.00%)  1/147 (0.68%) 
Cardiac disorders     
Bradycardia * 1  1/147 (0.68%)  1/147 (0.68%) 
Cardiac arrest * 1  1/147 (0.68%)  1/147 (0.68%) 
Cardiovascular insufficiency * 1  1/147 (0.68%)  0/147 (0.00%) 
Myocardial infarction * 1  0/147 (0.00%)  1/147 (0.68%) 
Palpitations * 1  0/147 (0.00%)  1/147 (0.68%) 
Tachyarrhythmia * 1  1/147 (0.68%)  0/147 (0.00%) 
Ventricular fibrillation * 1  0/147 (0.00%)  1/147 (0.68%) 
Gastrointestinal disorders     
Abdominal pain upper * 1  1/147 (0.68%)  0/147 (0.00%) 
Constipation * 1  1/147 (0.68%)  0/147 (0.00%) 
Diarrhoea * 1  0/147 (0.00%)  4/147 (2.72%) 
Gastric haemorrhage * 1  2/147 (1.36%)  0/147 (0.00%) 
Gastrointestinal haemorrhage * 1  1/147 (0.68%)  0/147 (0.00%) 
Intestinal obstruction * 1  1/147 (0.68%)  0/147 (0.00%) 
Nausea * 1  2/147 (1.36%)  0/147 (0.00%) 
Obstruction gastric * 1  2/147 (1.36%)  1/147 (0.68%) 
Odynophagia * 1  0/147 (0.00%)  1/147 (0.68%) 
Oesophageal haemorrhage * 1  0/147 (0.00%)  1/147 (0.68%) 
Upper gastrointestinal haemorrhage * 1  0/147 (0.00%)  1/147 (0.68%) 
Vomiting * 1  5/147 (3.40%)  3/147 (2.04%) 
General disorders     
Asthenia * 1  1/147 (0.68%)  0/147 (0.00%) 
Death * 1  1/147 (0.68%)  1/147 (0.68%) 
Pyrexia * 1  1/147 (0.68%)  0/147 (0.00%) 
Hepatobiliary disorders     
Drug-induced liver injury * 1  0/147 (0.00%)  1/147 (0.68%) 
Infections and infestations     
Appendicitis * 1  0/147 (0.00%)  1/147 (0.68%) 
Catheter site infection * 1  0/147 (0.00%)  1/147 (0.68%) 
Cellulitis * 1  0/147 (0.00%)  1/147 (0.68%) 
Infective spondylitis * 1  0/147 (0.00%)  1/147 (0.68%) 
Neutropenic sepsis * 1  0/147 (0.00%)  1/147 (0.68%) 
Pneumonia * 1  2/147 (1.36%)  2/147 (1.36%) 
Sepsis * 1  2/147 (1.36%)  1/147 (0.68%) 
Tinea pedis * 1  0/147 (0.00%)  1/147 (0.68%) 
Tooth infection * 1  1/147 (0.68%)  0/147 (0.00%) 
Urinary tract infection * 1  1/147 (0.68%)  0/147 (0.00%) 
Injury, poisoning and procedural complications     
Infusion related reaction * 1  0/147 (0.00%)  1/147 (0.68%) 
Lymphatic duct injury * 1  1/147 (0.68%)  0/147 (0.00%) 
Spinal compression fracture * 1  1/147 (0.68%)  0/147 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  2/147 (1.36%)  0/147 (0.00%) 
Diabetes mellitus * 1  1/147 (0.68%)  1/147 (0.68%) 
Electrolyte imbalance * 1  1/147 (0.68%)  0/147 (0.00%) 
Hypernatraemia * 1  1/147 (0.68%)  0/147 (0.00%) 
Hypoalbuminaemia * 1  0/147 (0.00%)  1/147 (0.68%) 
Hypocalcaemia * 1  0/147 (0.00%)  1/147 (0.68%) 
Hypoglycaemia * 1  0/147 (0.00%)  1/147 (0.68%) 
Hypokalaemia * 1  2/147 (1.36%)  1/147 (0.68%) 
Hyponatraemia * 1  0/147 (0.00%)  1/147 (0.68%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal chest pain * 1  0/147 (0.00%)  1/147 (0.68%) 
Nervous system disorders     
Cerebral ischaemia * 1  0/147 (0.00%)  1/147 (0.68%) 
Cerebrovascular accident * 1  1/147 (0.68%)  0/147 (0.00%) 
Dizziness * 1  0/147 (0.00%)  1/147 (0.68%) 
Haemorrhage intracranial * 1  1/147 (0.68%)  0/147 (0.00%) 
Renal and urinary disorders     
Acute kidney injury * 1  4/147 (2.72%)  2/147 (1.36%) 
Renal failure * 1  3/147 (2.04%)  0/147 (0.00%) 
Ureteric obstruction * 1  0/147 (0.00%)  1/147 (0.68%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease * 1  0/147 (0.00%)  1/147 (0.68%) 
Pneumonia aspiration * 1  0/147 (0.00%)  1/147 (0.68%) 
Pulmonary embolism * 1  1/147 (0.68%)  0/147 (0.00%) 
Vascular disorders     
Bleeding varicose vein * 1  0/147 (0.00%)  1/147 (0.68%) 
Deep vein thrombosis * 1  0/147 (0.00%)  1/147 (0.68%) 
Peripheral embolism * 1  0/147 (0.00%)  1/147 (0.68%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (18.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Capecitabine + Cisplatin + Herceptin (6 mg/kg) Capecitabine + Cisplatin + Herceptin (10 mg/kg)
Affected / at Risk (%) Affected / at Risk (%)
Total   123/147 (83.67%)   122/147 (82.99%) 
Blood and lymphatic system disorders     
Anaemia * 1  47/147 (31.97%)  40/147 (27.21%) 
Leukopenia * 1  26/147 (17.69%)  24/147 (16.33%) 
Neutropenia * 1  61/147 (41.50%)  69/147 (46.94%) 
Thrombocytopenia * 1  14/147 (9.52%)  14/147 (9.52%) 
Gastrointestinal disorders     
Abdominal pain * 1  8/147 (5.44%)  7/147 (4.76%) 
Abdominal pain upper * 1  12/147 (8.16%)  11/147 (7.48%) 
Constipation * 1  19/147 (12.93%)  25/147 (17.01%) 
Diarrhoea * 1  24/147 (16.33%)  30/147 (20.41%) 
Nausea * 1  55/147 (37.41%)  55/147 (37.41%) 
Vomiting * 1  36/147 (24.49%)  42/147 (28.57%) 
General disorders     
Asthenia * 1  16/147 (10.88%)  11/147 (7.48%) 
Fatigue * 1  25/147 (17.01%)  23/147 (15.65%) 
Oedema peripheral * 1  9/147 (6.12%)  6/147 (4.08%) 
Pyrexia * 1  15/147 (10.20%)  14/147 (9.52%) 
Investigations     
Weight decreased * 1  10/147 (6.80%)  17/147 (11.56%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  32/147 (21.77%)  27/147 (18.37%) 
Hypoalbuminaemia * 1  5/147 (3.40%)  10/147 (6.80%) 
Hypocalcaemia * 1  9/147 (6.12%)  9/147 (6.12%) 
Hypokalaemia * 1  6/147 (4.08%)  15/147 (10.20%) 
Hyponatraemia * 1  3/147 (2.04%)  8/147 (5.44%) 
Nervous system disorders     
Dizziness * 1  8/147 (5.44%)  2/147 (1.36%) 
Renal and urinary disorders     
Chronic kidney disease * 1  7/147 (4.76%)  13/147 (8.84%) 
Renal failure * 1  5/147 (3.40%)  8/147 (5.44%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  9/147 (6.12%)  3/147 (2.04%) 
Skin and subcutaneous tissue disorders     
Palmar-plantar erythrodysaesthesia syndrome * 1  14/147 (9.52%)  20/147 (13.61%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (18.0)
Trial was stopped for futility based on pre-planned interim analysis results.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01450696     History of Changes
Other Study ID Numbers: BO27798
2011-001526-19 ( EudraCT Number )
First Submitted: October 10, 2011
First Posted: October 12, 2011
Results First Submitted: October 5, 2016
Results First Posted: November 28, 2016
Last Update Posted: November 28, 2016