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)

简要总结

主要结局

次要结局

• Percentage of Participants With Clinical Benefit (Confirmed CR, PR, or Stable Disease [SD] ≥4 Months) in the CNS, Assessed Using RANO-BM Criteria(From Baseline until disease progression (assessed every 6 weeks for first 2 scans, followed by every 8 weeks for 2 scans, then every 12 weeks until disease progression; up to approximately 5 years))
• Median Duration of Response in the CNS, Assessed Using RANO-BM Criteria(From documentation of first complete response (CR) or partial response (PR) to the time of disease progression, relapse, or death from any cause, whichever occurred first (up to approximately 3.5 years))
• Overall Survival(From the date of first dose until death due to any cause (up to approximately 5 years))
• Median Duration of Clinical Benefit (Confirmed CR, PR, or SD ≥4 Months) in the CNS, Assessed Using RANO-BM Criteria(From documentation of first complete response (CR), partial response (PR), or stable disease (SD) ≥4 months to the date of disease progression, relapse, or death from any cause, whichever occurred first (up to approximately 5 years))
• Percentage of Participants With Clinical Benefit (Confirmed CR, PR, or SD ≥6 Months) in the CNS, Assessed Using RANO-BM Criteria(From Baseline until disease progression (assessed every 6 weeks for first 2 scans, followed by every 8 weeks for 2 scans, then every 12 weeks until disease progression; up to approximately 5 years))
• Median Duration of Clinical Benefit (Confirmed CR, PR, or SD ≥6 Months) in the CNS, Assessed Using RANO-BM Criteria(From documentation of first complete response (CR), partial response (PR), or stable disease (SD) ≥6 months to the date of disease progression, relapse, or death from any cause, whichever occurred first (up to approximately 5 years))
• Progression-Free Survival (CNS or Systemic), Assessed Using RANO-BM Criteria and RECIST v1.1(From the date of first dose to CNS or systemic disease progression or death from any cause, whichever occurred first (up to approximately 5 years))
• Number of Deaths by Time (≤30 or >30 Days) From Last Study Drug Administration and by Primary Cause of Death(From date of first dose until death due to any cause (up to approximately 5 years))
• Progression-Free Survival (CNS), Assessed Using RANO-BM Criteria(From the date of first dose to disease progression in the CNS or death from any cause, whichever occurred first (up to approximately 5 years))
• Number of Participants With at Least One TEAE Leading to Pertuzumab Infusion Delay, Slow Down, or Interruption, by Highest Grade of Severity According to NCI-CTCAE v4.0(From the first dose until 30 days after the last dose of study treatment (up to approximately 5 years))
• Number of Participants With at Least One TEAE Leading to Trastuzumab Dose Modification by Highest Grade of Severity According to NCI-CTCAE v4.0(From the first dose until 30 days after the last dose of study treatment (up to approximately 5 years))
• Percentage of Participants With at Least One TEAE of Special Interest by Highest Grade of Severity, According to NCI-CTCAE v4.0(From the first dose until 30 days after the last dose of study treatment (up to approximately 5 years))
• Number of Participants With NCI-CTCAE v4.0 Grades 3 and 4 Clinical Laboratory Abnormalities in Hematology Tests Over Time(Baseline, Weeks 18, 36, and 60 (up to approximately 5 years))
• Progression-Free Survival (Systemic), Assessed Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)(From the date of first dose to systemic disease progression or death from any cause, whichever occurred first (up to approximately 5 years))
• Number of Participants With at Least One Treatment-Emergent Serious Adverse Event (SAE) by Highest Grade of Severity, According to NCI-CTCAE v4.0(From the first dose until 30 days after the last dose of study treatment (up to approximately 5 years))
• Number of Participants With at Least One TEAE Leading to Withdrawal of Any Study Drug, Pertuzumab Only, or Both Pertuzumab and Trastuzumab, by Highest Grade of Severity According to NCI-CTCAE v4.0(From the first dose until 30 days after the last dose of study treatment (up to approximately 5 years))
• Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) by Highest Grade of Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0)(From the first dose until 30 days after the last dose of study treatment (up to approximately 5 years))
• Median Left Ventricular Ejection Fraction (LVEF) Values Over Time(Baseline, Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132 (Treatment Period); and every 3 months during Survival Follow-Up (up to approximately 5 years))
• Number of Participants With NCI-CTCAE v4.0 Grades 3 and 4 Clinical Laboratory Abnormalities in Blood Chemistry Tests Over Time(Weeks 6, 12, and 18, and Unscheduled Visits (up to approximately 5 years))
• Number of Participants by Investigator Interpretation of Left Ventricular Ejection Fraction (LVEF) Assessments Over Time(Baseline, Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132 (Treatment Period); and every 3 months during Survival Follow-Up (up to approximately 5 years))
• Observed Trough Serum Concentrations (Cmin) of Pertuzumab at Specified Timepoints(Pre-dose (0-4 hours) on Day 1 of Weeks 1, 4, 10, and 16)
• Maximum Serum Concentrations (Cmax) of Pertuzumab at Specified Timepoints(Post-infusion (0-30 minutes, infused over 60 minutes) on Day 1 of Week 1 and 16)
• Observed Trough Serum Concentrations (Cmin) of Trastuzumab at Specified Timepoints(Pre-dose (0-4 hours) on Day 1 of Weeks 1, 4, 10, and 16)
• Symptom Severity Scale Score Over Time, Assessed by Participant Reporting on the M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT) Questionnaire(Baseline, Weeks 6, 12, 20, 28, 40, 52, and 64)
• Maximum Serum Concentrations (Cmax) of Trastuzumab at Specified Timepoints(Post-infusion (0-30 minutes, infused over 60 minutes) on Day 1 of Week 1 and 16)
• Symptom Interference Scale Score Over Time, Assessed by Participant Reporting on the MDASI-BT Questionnaire(Baseline, Weeks 6, 12, 20, 28, 40, 52, and 64)