Description:
This study will examine the safety and efficacy of pertuzumab in combination with high-dose
trastuzumab in adult participants with HER2-positive MBC with CNS metastases and disease
progression in the brain following radiotherapy.
Title
- Brief Title: Pertuzumab With High-Dose Trastuzumab in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (MBC) With Central Nervous System (CNS) Progression Post-Radiotherapy
- Official Title: An Open-Label, Single-Arm, Phase II Study of Pertuzumab With High-Dose Trastuzumab for the Treatment of Central Nervous System Progression Post-Radiotherapy in Patients With HER2-Positive Metastatic Breast Cancer (PATRICIA)
Clinical Trial IDs
- ORG STUDY ID:
ML29366
- NCT ID:
NCT02536339
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Pertuzumab | Perjeta | Pertuzumab + Trastuzumab |
| Trastuzumab | Herceptin | Pertuzumab + Trastuzumab |
Purpose
This study will examine the safety and efficacy of pertuzumab in combination with high-dose
trastuzumab in adult participants with HER2-positive MBC with CNS metastases and disease
progression in the brain following radiotherapy.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Pertuzumab + Trastuzumab | Experimental | Participants with CNS metastases secondary to HER2-positive MBC will receive pertuzumab in combination with high-dose trastuzumab until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. | |
Eligibility Criteria
Inclusion Criteria:
- Pathologically confirmed HER2-positive MBC
- Progression of or new brain metastases after completion of whole-brain radiotherapy or
stereotactic radiosurgery
- Completion of whole-brain radiotherapy or stereotactic radiosurgery more than 60 days
prior to enrollment
- Stable systemic disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- LVEF at least 50%
- Adequate hematologic, renal, and hepatic function
- Life expectancy more than 12 weeks
Exclusion Criteria:
- Progression of systemic disease at Screening
- Leptomeningeal disease
- History of intolerance or hypersensitivity to study drug
- Use of certain investigational therapies within 21 days prior to enrollment
- Current anthracycline use
- Unwillingness to discontinue ado-trastuzumab emtansine or lapatinib use
- Active infection
- Pregnant or lactating women
- Significant history or risk of cardiac disease
- Symptomatic intrinsic lung disease or lung involvement
- History of other malignancy within the last 5 years
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Percentage of Participants With Objective Response (OR) in the CNS Assessed per Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) Criteria |
| Time Frame: | Baseline up to approximately 3 years (assessed every 6 week for first 2 scans, then every 8 weeks for subsequent 2 scans, followed by every 12 weeks until disease progression, at the treatment discontinuation visit) |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Percentage of Participants With Drop in Left Ventricular Ejection Fraction (LVEF) of at Least 10 Points From Baseline and to Below 50 Percent (%) |
| Time Frame: | Baseline until death due to any cause (assessed at Week 6 and 12, followed by every 3 months during treatment period, then every 6 months up to approximately 3 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Response (DOR) in the CNS |
| Time Frame: | Baseline up to approximately 3 years (assessed every 6 week for first 2 scans, then every 8 weeks for subsequent 2 scans, followed by every 12 weeks until disease progression, at the treatment discontinuation visit) |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants With Clinical Benefit in the CNS as Assessed Using RANO-BM Criteria |
| Time Frame: | Baseline up to approximately 3 years (assessed every 6 week for first 2 scans, then every 8 weeks for subsequent 2 scans, followed by every 12 weeks until disease progression, at the treatment discontinuation visit) |
| Safety Issue: | |
| Description: | |
| Measure: | Progression Free Survival - in the CNS as Assessed Using RANO-BM Criteria |
| Time Frame: | Baseline up to approximately 3 years (assessed every 6 week for first 2 scans, then every 8 weeks for subsequent 2 scans, followed by every 12 weeks until disease progression, at the treatment discontinuation visit) |
| Safety Issue: | |
| Description: | |
| Measure: | Progression Free Survival Systemically as Assessed Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) |
| Time Frame: | Baseline up to approximately 3 years (assessed every 8 weeks for the first 16 weeks, then every 12 weeks until disease progression) |
| Safety Issue: | |
| Description: | |
| Measure: | Overall Survival |
| Time Frame: | Baseline until death due to any cause (up to approximately 3 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants With Adverse Events and Serious Adverse Events |
| Time Frame: | Baseline up to approximately 3 years |
| Safety Issue: | |
| Description: | |
| Measure: | Serum Pertuzumab Concentrations |
| Time Frame: | pre-dose (0 − 4 hours) and post-infusion (0 - 30 minutes, infused over 60 minutes) on Day 1 of Week 1 and 16, pre-dose (0 − 4 hours) on Day 1 of Week 4 and Week 10 |
| Safety Issue: | |
| Description: | |
| Measure: | Serum Trastuzumab Concentrations |
| Time Frame: | pre-dose (0 − 4 hours) and post-infusion (0 - 30 minutes, infused over 30 - 90 minutes) on Day 1 of Week 1 and 16, pre-dose (0 − 4 hours) on Day 1 of Week 4 and Week 10 |
| Safety Issue: | |
| Description: | |
| Measure: | M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT) Assessment Score |
| Time Frame: | Baseline, every 6 weeks, followed by every 8 weeks, then every 12 weeks until progression (up to approximately 3 years) |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Genentech, Inc. |
Last Updated
January 11, 2018
