Breast Cancer
Conditions
Brief summary
This study will assess the efficacy and safety of intravenous (IV) trastuzumab (Herceptin) and IV docetaxel (Taxotere), with or without oral capecitabine (Xeloda), in women with previously untreated HER2-positive advanced and/or metastatic breast cancer.
Interventions
DRUGXeloda
Participants will receive oral Xeloda, 950 mg/m\^2 twice a day on Days 1 to 14 of each 21-day cycle.
DRUGTaxotere
Participants will receive Taxotere, 75 milligrams per meter-squared (mg/m\^2) in the Herceptin + Taxotere + Xeloda arm or 100 mg/m\^2 in the Herceptin + Taxotere arm, via IV infusion on Day 1 of each 21-day cycle. The lower starting dose will be used in the triple-therapy arm.
DRUGHerceptin
Participants will receive Herceptin, 6 milligrams per kilogram (mg/kg) via IV infusion, on Day 1 of each 21-day cycle. The first dose will be a loading dose of 8 mg/kg in Cycle 1; the dose of 6 mg/kg will be given from Cycle 2 onward.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed, HER2-positive advanced and/or metastatic breast cancer not amenable to curative therapy * At least one measurable lesion according to RECIST * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Baseline left ventricular ejection fraction (LVEF) at least 50%
Exclusion criteria
* Pregnant, lactating, or women of childbearing potential who are not surgically sterile or not willing to use adequate contraceptive methods * Previous treatment with Herceptin or other anti-HER therapies, or any previous chemotherapy for advanced or metastatic disease * Past medical history significant for any cardiac or central nervous system (CNS) disorders * Poor hematologic, renal, or hepatic function * Chronic corticosteroid therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) | Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall) | Tumor response was assessed by RECIST during the study. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a best overall response for CR or PR was reported. The exact 95% confidence interval (CI) for one-sample binomial was determined using the Pearson-Clopper method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Death or Disease Progression According to RECIST | Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall) | Tumor response was assessed by RECIST during the study. Disease progression or progressive disease (PD) was defined as ≥20% increase in sum LD in reference to the smallest on-treatment sum LD, or the appearance of new lesions. The percentage of participants who died or experienced PD was reported. |
| Progression-Free Survival (PFS) According to RECIST | Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall) | Tumor response was assessed by RECIST during the study. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-treatment sum LD, or the appearance of new lesions. PFS was defined as the time from start of treatment to the first event of death or PD. Participants without event at the time of analysis were censored at the latest date of last tumor assessment or last date in drug log. The median duration of PFS and corresponding 95% CI were estimated by Kaplan-Meier analysis and expressed in months. |
| Percentage of Participants Who Died | Continuously during treatment (up to 66 months) and at any time after treatment discontinuation until 18 months after last participant enrolled (up to 66 months overall) | The percentage of participants who died from any cause was reported. |
| Overall Survival (OS) | Continuously during treatment (up to 66 months) and at any time after treatment discontinuation until 18 months after last participant enrolled (up to 66 months overall) | OS was defined as the time from start of treatment to date of death for any reason. Participants who were alive at the time of analysis were censored at the latest date of last tumor assessment, last drug intake, or last follow-up information. The median duration of OS and corresponding 95% CI were estimated by Kaplan-Meier analysis and expressed in months. |
| Duration of Response (DOR) According to RECIST | Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall) | Tumor response was assessed by RECIST during the study. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. PR was defined as ≥30% decrease in sum LD of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. DOR was defined as the time from first assessment of CR or PR until the first occurrence of documented PD, death, or withdrawal. The median DOR was reported and expressed in months. |
Countries
Australia, Brazil, Canada, Costa Rica, Finland, France, Greece, Guatemala, Italy, Mexico, Panama, Poland, Spain, Sweden, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Herceptin + Taxotere + Xeloda Participants received triple therapy with Herceptin, Taxotere, and Xeloda until disease progression, unmanageable toxicity, or withdrawal. Herceptin and Taxotere were given via IV infusion on Day 1 of each 21-day cycle. The first dose of Herceptin was a loading dose of 8 mg/kg in Cycle 1, and a maintenance dose of 6 mg/kg was given from Cycle 2 through the end of treatment. The dose of Taxotere was 75 mg/m\^2, with adjustments allowed only for toxicity. Xeloda was given orally as 950 mg/m\^2 twice a day on Days 1 to 14 of each 21-day cycle, with adjustments allowed only for toxicity. | 112 |
| Herceptin + Taxotere Participants received dual therapy with Herceptin and Taxotere until disease progression, unmanageable toxicity, or withdrawal. Treatments were given via IV infusion on Day 1 of each 21-day cycle. The first dose of Herceptin was a loading dose of 8 mg/kg in Cycle 1, and a maintenance dose of 6 mg/kg was given from Cycle 2 through the end of treatment. The dose of Taxotere was 100 mg/m\^2, with adjustments allowed only for toxicity. | 110 |
| Total | 222 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal Laboratory Test | 1 | 0 |
| Overall Study | Adverse Event or Intercurrent Illness | 5 | 11 |
| Overall Study | Death | 5 | 3 |
| Overall Study | Failure to Return | 1 | 0 |
| Overall Study | Insufficient Therapeutic Response | 56 | 57 |
| Overall Study | Other | 30 | 29 |
| Overall Study | Protocol Violation | 6 | 4 |
| Overall Study | Refused Treatment* | 6 | 6 |
| Overall Study | Violation of Selection Criteria | 2 | 0 |
| Overall Study | Withdrawal Prior to Treatment | 1 | 2 |
Baseline characteristics
| Characteristic | Herceptin + Taxotere + Xeloda | Herceptin + Taxotere | Total |
|---|---|---|---|
| Age, Continuous | 52.7 years STANDARD_DEVIATION 11.18 | 51.6 years STANDARD_DEVIATION 10.74 | 52.1 years STANDARD_DEVIATION 10.95 |
| Sex: Female, Male Female | 112 Participants | 110 Participants | 222 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 112 / 112 | 107 / 110 |
| serious Total, serious adverse events | 52 / 112 | 51 / 110 |
Outcome results
Primary
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Tumor response was assessed by RECIST during the study. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a best overall response for CR or PR was reported. The exact 95% confidence interval (CI) for one-sample binomial was determined using the Pearson-Clopper method.
Time frame: Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall)
Population: Full Analysis Set (FAS) Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Herceptin + Taxotere + Xeloda | Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) | 70.5 percentage of participants |
| Herceptin + Taxotere | Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) | 72.7 percentage of participants |
p-value: 0.71795% CI: [-10.17, 14.56]Chi-squared
Secondary
Duration of Response (DOR) According to RECIST
Tumor response was assessed by RECIST during the study. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. PR was defined as ≥30% decrease in sum LD of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. DOR was defined as the time from first assessment of CR or PR until the first occurrence of documented PD, death, or withdrawal. The median DOR was reported and expressed in months.
Time frame: Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall)
Population: FAS Population. The Number of Participants Analyzed reflects the number of participants with a best overall response of CR or PR who provided evaluable data for the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Herceptin + Taxotere + Xeloda | Duration of Response (DOR) According to RECIST | 15.9 months |
| Herceptin + Taxotere | Duration of Response (DOR) According to RECIST | 13.4 months |
Secondary
Overall Survival (OS)
OS was defined as the time from start of treatment to date of death for any reason. Participants who were alive at the time of analysis were censored at the latest date of last tumor assessment, last drug intake, or last follow-up information. The median duration of OS and corresponding 95% CI were estimated by Kaplan-Meier analysis and expressed in months.
Time frame: Continuously during treatment (up to 66 months) and at any time after treatment discontinuation until 18 months after last participant enrolled (up to 66 months overall)
Population: FAS Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Herceptin + Taxotere + Xeloda | Overall Survival (OS) | 43.5 months |
| Herceptin + Taxotere | Overall Survival (OS) | 47.3 months |
p-value: 0.475895% CI: [0.56, 1.32]Log Rank
Secondary
Percentage of Participants Who Died
The percentage of participants who died from any cause was reported.
Time frame: Continuously during treatment (up to 66 months) and at any time after treatment discontinuation until 18 months after last participant enrolled (up to 66 months overall)
Population: FAS Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Herceptin + Taxotere + Xeloda | Percentage of Participants Who Died | 35.7 percentage of participants |
| Herceptin + Taxotere | Percentage of Participants Who Died | 41.8 percentage of participants |
Secondary
Percentage of Participants With Death or Disease Progression According to RECIST
Tumor response was assessed by RECIST during the study. Disease progression or progressive disease (PD) was defined as ≥20% increase in sum LD in reference to the smallest on-treatment sum LD, or the appearance of new lesions. The percentage of participants who died or experienced PD was reported.
Time frame: Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall)
Population: FAS Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Herceptin + Taxotere + Xeloda | Percentage of Participants With Death or Disease Progression According to RECIST | 67.9 percentage of participants |
| Herceptin + Taxotere | Percentage of Participants With Death or Disease Progression According to RECIST | 77.3 percentage of participants |
Secondary
Progression-Free Survival (PFS) According to RECIST
Tumor response was assessed by RECIST during the study. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-treatment sum LD, or the appearance of new lesions. PFS was defined as the time from start of treatment to the first event of death or PD. Participants without event at the time of analysis were censored at the latest date of last tumor assessment or last date in drug log. The median duration of PFS and corresponding 95% CI were estimated by Kaplan-Meier analysis and expressed in months.
Time frame: Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall)
Population: FAS Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Herceptin + Taxotere + Xeloda | Progression-Free Survival (PFS) According to RECIST | 17.9 months |
| Herceptin + Taxotere | Progression-Free Survival (PFS) According to RECIST | 12.8 months |
p-value: 0.044995% CI: [0.53, 0.99]Log Rank