A Study of Herceptin (Trastuzumab) in Combination With Whole Brain Radiotherapy in Patients With HER-2 Positive Breast Cancer

Study Overview
=================
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.

Official Title
-----------------
A Multicenter, Open Label Study to Assess the Effect of Trastuzumab + Whole Brain Radiotherapy (WBRT) on Brain Metastases From HER-2 Positive Breast Cancer. (bHERt-2)

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: trastuzumab [Herceptin]


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trastuzumab Monotherapy<br>Participants received an initial loading dose of 4 milligrams per kilogram (mg/kg) trastuzumab intravenous (i.v.), followed by weekly doses of 2 mg/kg i.v. for up to 18 weeks. | Drug: trastuzumab [Herceptin]<br>* Initial loading dose of 4 mg/kg i.v. infusion, followed by weekly doses of 2 mg/kg for up to 18 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Cycle 7 (Week 7, approximately 5 weeks after completion of whole brain radiotherapy [WBRT]) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Cycle 15 (Week 15, approximately 13 weeks after completion of WBRT) | 
| 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. | BL and 4 weeks after Cycle 15 (Week 15, approximately 13 weeks after completion of WBRT) or the last dose of study treatment | 
| Overall Survival | The number of participants surviving at the final visit. | 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 | 
| 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. | 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 |