Breast Cancer
Conditions
Brief summary
This single-arm, multicenter, open-label study will evaluate the efficacy and safety of Herceptin (trastuzumab) in combination with whole brain radiotherapy on brain metastases in patients with HER-2 positive breast cancer. The patients will receive Herceptin 4 mg/kg (loading dose) followed by 2 mg/kg for a maximum of 18 weekly cycles. The anticipated time on study treatment is 18 weeks.
Interventions
Initial loading dose of 4 mg/kg i.v. infusion, followed by weekly doses of 2 mg/kg for up to 18 weeks.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/=18 years of age * Diagnosis of breast carcinoma with HER-2 overexpression * At least one measurable brain metastasis * Patients for whom, according to investigator assessment, whole brain radiotherapy is the best therapeutic option * Performance status (WHO) \</=2 * Life expectancy \>/=3 months
Exclusion criteria
* Presence of neoplastic meningitis * Any prior radiotherapy to the brain * Patients for whom, according to investigator assessment, stereotactic radiotherapy is the best therapeutic option * Previous neoplasms, other than breast carcinoma, within 5 years since enrolment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Brain Objective Response According to Response Evaluation Criteria In Solid Tumors (RECIST) Criteria at Cycle 7 | Baseline and Cycle 7 (Week 7, approximately 5 weeks after completion of whole brain radiotherapy [WBRT]) | Brain objective response was defined as either a complete response (CR) or partial response (PR), provided that there was no increase in steroid requirements or worsening of neurological signs and symptoms. CR was defined as the disappearance of all central nervous system (CNS) lesions. PR was defined as a greater than or equal to (≥) 30 percent (%) reduction in the volumetric sum of all measurable CNS lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Brain Objective Response According to RECIST Criteria at Cycle 15 | Baseline and Cycle 15 (Week 15, approximately 13 weeks after completion of WBRT) | Brain objective response was defined as either a CR or PR, provided that there was no increase in steroid requirements or worsening of neurological signs and symptoms. CR was defined as the disappearance of all CNS lesions. PR was defined as ≥30% reduction in the volumetric sum of all measurable CNS lesions. |
| Number of Participants With Brain Objective Response Defined According to RECIST Criteria at the Final Visit | BL and 4 weeks after Cycle 15 (Week 15, approximately 13 weeks after completion of WBRT) or the last dose of study treatment | Brain objective response was defined as either a CR or PR), provided that there was no increase in steroid requirements, or worsening of neurological signs and symptoms. CR was defined as the disappearance of all CNS lesions. PR was defined as ≥30% reduction in the volumetric sum of all measurable CNS lesions. |
| Overall Survival | Baseline, weekly for 3 weeks (pre-WBRT phase), Cycles 1 through 15 (treatment phase Weeks 1 through 15), and 4 weeks after Cycle 15 (Week 15) or the last dose of study treatment | The number of participants surviving at the final visit. |
| Brain Progression-Free Survival (B-PFS) | Baseline, weekly for 3 weeks (pre-WBRT phase), Cycles 1 through 15 (treatment phase Weeks 1 through 15), and 4 weeks after Cycle 15 (Week 15) or the last dose of study treatment | B-PFS was defined as the time from the date of first study drug assumption and the date of documented evidence of brain progression (defined as appearance of new brain metastases or progression of pre-existing lesions) or death for brain progression, whichever came first. Progression in other metastatic sites, deaths not due to brain-progression and withdrawals due to adverse events were to be considered as competing risk. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab Monotherapy Participants received an initial loading dose of 4 mg/kg trastuzumab i.v. on Day 1, followed by doses of 2 mg/kg trastuzumab i.v. once weekly for up to 18 weeks. | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease progression | 1 |
Baseline characteristics
| Characteristic | Trastuzumab Monotherapy |
|---|---|
| Age, Continuous | 60 years |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Number of Participants With Brain Objective Response According to Response Evaluation Criteria In Solid Tumors (RECIST) Criteria at Cycle 7
Brain objective response was defined as either a complete response (CR) or partial response (PR), provided that there was no increase in steroid requirements or worsening of neurological signs and symptoms. CR was defined as the disappearance of all central nervous system (CNS) lesions. PR was defined as a greater than or equal to (≥) 30 percent (%) reduction in the volumetric sum of all measurable CNS lesions.
Time frame: Baseline and Cycle 7 (Week 7, approximately 5 weeks after completion of whole brain radiotherapy [WBRT])
Population: ITT population; 1 participant was not assessed at Cycle 7.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Monotherapy | Number of Participants With Brain Objective Response According to Response Evaluation Criteria In Solid Tumors (RECIST) Criteria at Cycle 7 | 2 participants |
Secondary
Brain Progression-Free Survival (B-PFS)
B-PFS was defined as the time from the date of first study drug assumption and the date of documented evidence of brain progression (defined as appearance of new brain metastases or progression of pre-existing lesions) or death for brain progression, whichever came first. Progression in other metastatic sites, deaths not due to brain-progression and withdrawals due to adverse events were to be considered as competing risk.
Time frame: Baseline, weekly for 3 weeks (pre-WBRT phase), Cycles 1 through 15 (treatment phase Weeks 1 through 15), and 4 weeks after Cycle 15 (Week 15) or the last dose of study treatment
Population: Due to the premature interruption of the study and the small number of enrolled participants (3 nerolled), all participant data were listed only, without any descriptive statistics or data analysis. The endpoint of B-PFS was thus not analyzed.
Secondary
Number of Participants With Brain Objective Response According to RECIST Criteria at Cycle 15
Brain objective response was defined as either a CR or PR, provided that there was no increase in steroid requirements or worsening of neurological signs and symptoms. CR was defined as the disappearance of all CNS lesions. PR was defined as ≥30% reduction in the volumetric sum of all measurable CNS lesions.
Time frame: Baseline and Cycle 15 (Week 15, approximately 13 weeks after completion of WBRT)
Population: ITT population; 2 participants were not assessed at Cycle 15.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Monotherapy | Number of Participants With Brain Objective Response According to RECIST Criteria at Cycle 15 | 0 participants |
Secondary
Number of Participants With Brain Objective Response Defined According to RECIST Criteria at the Final Visit
Brain objective response was defined as either a CR or PR), provided that there was no increase in steroid requirements, or worsening of neurological signs and symptoms. CR was defined as the disappearance of all CNS lesions. PR was defined as ≥30% reduction in the volumetric sum of all measurable CNS lesions.
Time frame: BL and 4 weeks after Cycle 15 (Week 15, approximately 13 weeks after completion of WBRT) or the last dose of study treatment
Population: ITT population; 1 participant was not assessed at the final visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Monotherapy | Number of Participants With Brain Objective Response Defined According to RECIST Criteria at the Final Visit | 1 participant |
Secondary
Overall Survival
The number of participants surviving at the final visit.
Time frame: Baseline, weekly for 3 weeks (pre-WBRT phase), Cycles 1 through 15 (treatment phase Weeks 1 through 15), and 4 weeks after Cycle 15 (Week 15) or the last dose of study treatment
Population: ITT population; survival status of 1 participant was unknown at the final visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Monotherapy | Overall Survival | 1 participant |