Breast Cancer
Conditions
Brief summary
This 2 arm study will assess the efficacy and safety of intravenous Herceptin with or without a taxane for the first line treatment of metastatic breast cancer in women who have relapsed at least 12 months after a minimum of 10 months of (neo)adjuvant treatment with Herceptin for HER2-positive early breast cancer.Patients will receive either Herceptin monotherapy (loading dose of 4mg/kg iv, followed by weekly doses of 2mg/kg iv, or 8mg/kg loading dose followed by 3-weekly doses of 6mg/kg)or Herceptin + a taxane (docetaxel 100mg/m2 iv every 3 weeks, or paclitaxel 175mg/m2 iv every 3 weeks or 75mg/m2 every week). The anticipated time on study treatment is until disease progression, and the target sample size is \<100 individuals.
Interventions
DRUGTrastuzumab
4 mg/kg i.v. loading dose on Day 1, followed by 2 mg/kg i.v. weekly; or 8 mg/kg i.v. loading dose, followed by 6 mg/kg i.v. every 3 weeks until disease progression, unacceptable toxicity, withdrawal or death.
DRUGTaxane (docetaxel or paclitaxel)
Docetaxel 100 mg/m2 i.v. every 3 weeks, or paclitaxel administered in a dose of 75 mg/m2 i.v. weekly or 175 mg/m2 i.v. every 3 weeks for at least 18 weeks, or more at the discretion of the investigator. Choice of taxane at the discretion of the investigator. Taxane may be administered at the same time, or 24 hours after, administration of trastuzumab.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* at least 10 months of Herceptin treatment for HER2-positive early breast cancer; * metastatic breast cancer \>=12 months after discontinuation of Herceptin; * measurable disease.
Exclusion criteria
* previous chemotherapy for metastatic breast cancer; * brain metastases; * invasive malignancy other than metastatic breast cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 Guidelines | Baseline (BL); Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited | CR was defined for target lesions (TLs) as the disappearance of all lesions, and for nontarget lesions (NTLs) as the disappearance of all nontarget nonmeasurable lesions. PR was defined for TLs as at least a 30 percent (%) decrease from baseline (BL) in the sum of longest diameter (SLD) of TLs. 95% confidence interval for one-sample binomial using Pearson-Clopper method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited | The time, in months, from when the response (CR or PR) was first noted until the date of documented PD, death, or withdrawal, whichever occurred first. Participants were censored at the date of the last tumor assessment. |
| Progression-free Survival (PFS) - Percentage of Participants With Progressive Disease | BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited | PFS was defined as the time from day of first study drug infusion until death or PD. Participants were censored at the date of the last tumor assessment. |
| Progression-Free Survival | BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited | The time, in months, from BL to PFS event. |
| Percentage of Participants With Treatment Failure | BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited | Treatment failure was defined as the time from first study drug infusion to failure. Failure was defined as any of the following: PD, death, withdrawal due to adverse event (AE) or lab abnormality, or refusal of treatment. Participants were censored at the last date recorded in the case report form (CRF) or the date of withdrawal. |
| Duration of Response - Percentage of Participants With Progressive Disease or Death | BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited | Duration of response was defined as the time from first confirmed CR or PR until death or progressive disease (PD). For TLs, PD was defined as at least a 20% increase in the SLD of the TL, taking as reference the smallest SLD recorded since the beginning of treatment or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of one or more new lesions or unequivocal progression of existing non target non-measurable lesions. Participants were censored at the date of the last tumor assessment. |
| Percentage of Participants With Clinical Benefit According to RECIST Guidelines | BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited | Clinical benefit was defined as stable disease (SD) for 6 months or longer, or a confirmed overall response of CR or PR. For TLs, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD since the beginning of treatment. For NTLs, SD was synonymous with incomplete response and defined as the persistence of one or more NTLs and/or maintenance of tumor marker level above the normal limits. |
| Overall Survival - Percentage of Participants Who Died | BL, Day 1 of Weeks 1, 4, 7, 10, 13, 16, 19, 25, 37, and 5 at the last administration of study treatment, every 24 weeks thereafter until disease progression or death, yearly thereafter up to 2 years after cessation of recruitment | OS was defined as the time from the date of enrollment to the date of death due to any cause. Participants were censored at the last date recorded in the CRF. |
| Overall Survival | BL, Day 1 of Weeks 1, 4, 7, 10, 13, 16, 19, 25, 37, and 52 at the last administration of study treatment, every 24 weeks thereafter until disease progression or death, yearly thereafter up to 2 years after cessation of recruitment | The time, in months, from BL to death due to any cause. |
| Time to Treatment Failure | BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited | The time, in months, from BL to treatment failure. |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Germany, Hungary, Italy, Mexico, Panama, Poland, Russia, Spain, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab Monotherapy Participants received either an initial loading dose of trastuzumab 4 mg/kg, IV, on Day 1, followed by 2 mg/kg, IV, once per week, or an initial loading dose of 8 mg/kg IV on Day 1, followed by 6 mg/kg IV once every 3 weeks, until disease progression, unacceptable toxicity, withdrawal or death. | 3 |
| Trastuzumab, Taxane Participants received either an initial loading dose of trastuzumab 4 mg/kg IV on Day 1, followed by 2 mg/kg IV once per week, or an initial loading dose of 8 mg/kg IV on Day 1, followed by 6 mg/kg IV every 3 weeks, until disease progression, unacceptable toxicity, withdrawal or death. Participants also received one of the following taxanes (at the investigator's discretion) for at least 18 weeks: docetaxel 100 mg/m\^2, IV, once every 3 weeks, OR, paclitaxel 75 mg/m\^2, IV, once per week, OR, paclitaxel 175 mg/m\^2, IV, once every 3 weeks. | 41 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Failure to Return | 0 | 1 |
| Overall Study | Lack of Efficacy | 3 | 34 |
| Overall Study | Other | 0 | 3 |
| Overall Study | Refused treatment | 0 | 2 |
Baseline characteristics
| Characteristic | Trastuzumab Monotherapy | Trastuzumab, Taxane | Total |
|---|---|---|---|
| Age, Continuous | 40 years | 54 years | 54 years |
| Sex: Female, Male Female | 3 Participants | 41 Participants | 44 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 | 3 / 3 | 36 / 41 |
| serious Total, serious adverse events | 0 / 3 | 6 / 41 |
Outcome results
Primary
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 Guidelines
CR was defined for target lesions (TLs) as the disappearance of all lesions, and for nontarget lesions (NTLs) as the disappearance of all nontarget nonmeasurable lesions. PR was defined for TLs as at least a 30 percent (%) decrease from baseline (BL) in the sum of longest diameter (SLD) of TLs. 95% confidence interval for one-sample binomial using Pearson-Clopper method.
Time frame: Baseline (BL); Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
Population: FAS; Cohort A (trastuzumab monotherapy) was closed prematurely due to enrollment difficulties. Therefore, Cohort A included only 3 participants and none of the data from these 3 participants were analyzed for any of the specified endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab, Taxane | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 Guidelines | 61.0 percentage of participants |
Secondary
Duration of Response
The time, in months, from when the response (CR or PR) was first noted until the date of documented PD, death, or withdrawal, whichever occurred first. Participants were censored at the date of the last tumor assessment.
Time frame: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
Population: FAS. Duration of response was assessed in participants with a best overall response of CR or PR. Cohort A (trastuzumab monotherapy) was closed prematurely due to enrollment difficulties. Therefore, Cohort A included only 3 participants and none of the data from these 3 participants were analyzed for any of the specified endpoints.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab, Taxane | Duration of Response | 8.0 months |
Secondary
Duration of Response - Percentage of Participants With Progressive Disease or Death
Duration of response was defined as the time from first confirmed CR or PR until death or progressive disease (PD). For TLs, PD was defined as at least a 20% increase in the SLD of the TL, taking as reference the smallest SLD recorded since the beginning of treatment or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of one or more new lesions or unequivocal progression of existing non target non-measurable lesions. Participants were censored at the date of the last tumor assessment.
Time frame: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
Population: FAS. Duration of response was assessed in participants with a best overall response of CR or PR. Cohort A (trastuzumab monotherapy) was closed prematurely due to enrollment difficulties. Therefore, Cohort A included only 3 participants and none of the data from these 3 participants were analyzed for any of the specified endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab, Taxane | Duration of Response - Percentage of Participants With Progressive Disease or Death | 88.0 percentage of participants |
Secondary
Overall Survival
The time, in months, from BL to death due to any cause.
Time frame: BL, Day 1 of Weeks 1, 4, 7, 10, 13, 16, 19, 25, 37, and 52 at the last administration of study treatment, every 24 weeks thereafter until disease progression or death, yearly thereafter up to 2 years after cessation of recruitment
Population: FAS; Cohort A (trastuzumab monotherapy) was closed prematurely due to enrollment difficulties. Therefore, Cohort A included only 3 participants and none of the data from these 3 participants were analyzed for any of the specified endpoints.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab, Taxane | Overall Survival | 25.0 months |
Secondary
Overall Survival - Percentage of Participants Who Died
OS was defined as the time from the date of enrollment to the date of death due to any cause. Participants were censored at the last date recorded in the CRF.
Time frame: BL, Day 1 of Weeks 1, 4, 7, 10, 13, 16, 19, 25, 37, and 5 at the last administration of study treatment, every 24 weeks thereafter until disease progression or death, yearly thereafter up to 2 years after cessation of recruitment
Population: FAS; Cohort A (trastuzumab monotherapy) was closed prematurely due to enrollment difficulties. Therefore, Cohort A included only 3 participants and none of the data from these 3 participants were analyzed for any of the specified endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab, Taxane | Overall Survival - Percentage of Participants Who Died | 63.4 percentage of participants |
Secondary
Percentage of Participants With Clinical Benefit According to RECIST Guidelines
Clinical benefit was defined as stable disease (SD) for 6 months or longer, or a confirmed overall response of CR or PR. For TLs, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD since the beginning of treatment. For NTLs, SD was synonymous with incomplete response and defined as the persistence of one or more NTLs and/or maintenance of tumor marker level above the normal limits.
Time frame: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
Population: FAS; Cohort A (trastuzumab monotherapy) was closed prematurely due to enrollment difficulties. Therefore, Cohort A included only 3 participants and none of the data from these 3 participants were analyzed for any of the specified endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab, Taxane | Percentage of Participants With Clinical Benefit According to RECIST Guidelines | 70.7 percentage of participants |
Secondary
Percentage of Participants With Treatment Failure
Treatment failure was defined as the time from first study drug infusion to failure. Failure was defined as any of the following: PD, death, withdrawal due to adverse event (AE) or lab abnormality, or refusal of treatment. Participants were censored at the last date recorded in the case report form (CRF) or the date of withdrawal.
Time frame: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
Population: FAS; Cohort A (trastuzumab monotherapy) was closed prematurely due to enrollment difficulties. Therefore, Cohort A included only 3 participants and none of the data from these 3 participants were analyzed for any of the specified endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab, Taxane | Percentage of Participants With Treatment Failure | 95.1 percentage of participants |
Secondary
Progression-Free Survival
The time, in months, from BL to PFS event.
Time frame: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
Population: FAS; Cohort A (trastuzumab monotherapy) was closed prematurely due to enrollment difficulties. Therefore, Cohort A included only 3 participants and none of the data from these 3 participants were analyzed for any of the specified endpoints.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab, Taxane | Progression-Free Survival | 8.0 months |
Secondary
Progression-free Survival (PFS) - Percentage of Participants With Progressive Disease
PFS was defined as the time from day of first study drug infusion until death or PD. Participants were censored at the date of the last tumor assessment.
Time frame: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
Population: FAS; Cohort A (trastuzumab monotherapy) was closed prematurely due to enrollment difficulties. Therefore, Cohort A included only 3 participants and none of the data from these 3 participants were analyzed for any of the specified endpoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab, Taxane | Progression-free Survival (PFS) - Percentage of Participants With Progressive Disease | 87.8 percentage of participants |
Secondary
Time to Treatment Failure
The time, in months, from BL to treatment failure.
Time frame: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
Population: FAS; Cohort A (trastuzumab monotherapy) was closed prematurely due to enrollment difficulties. Therefore, Cohort A included only 3 participants and none of the data from these 3 participants were analyzed for any of the specified endpoints.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab, Taxane | Time to Treatment Failure | 8.0 months |