Clinical trial NCT02536339: A Study of Pertuzumab With High-Dose Trastuzumab for the Treatment of 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2015-08-31
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: Percentage of Participants With Objective Response in the CNS, Assessed Using Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) Criteria
timeFrame: 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 3.5 years)
Secondary outcomes:
measure: Median Duration of Response in the CNS, Assessed Using RANO-BM Criteria
timeFrame: 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)
measure: Percentage of Participants With Clinical Benefit (Confirmed CR, PR, or Stable Disease [SD] ≥4 Months) in the CNS, Assessed Using RANO-BM Criteria
timeFrame: 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)
measure: Median Duration of Clinical Benefit (Confirmed CR, PR, or SD ≥4 Months) in the CNS, Assessed Using RANO-BM Criteria
timeFrame: 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)
measure: Percentage of Participants With Clinical Benefit (Confirmed CR, PR, or SD ≥6 Months) in the CNS, Assessed Using RANO-BM Criteria
timeFrame: 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)
measure: Median Duration of Clinical Benefit (Confirmed CR, PR, or SD ≥6 Months) in the CNS, Assessed Using RANO-BM Criteria
timeFrame: 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)
measure: Progression-Free Survival (CNS), Assessed Using RANO-BM Criteria
timeFrame: 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)
measure: Progression-Free Survival (Systemic), Assessed Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
timeFrame: From the date of first dose to systemic disease progression or death from any cause, whichever occurred first (up to approximately 5 years)
measure: Progression-Free Survival (CNS or Systemic), Assessed Using RANO-BM Criteria and RECIST v1.1
timeFrame: 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)
measure: Overall Survival
timeFrame: From the date of first dose until death due to any cause (up to approximately 5 years)
measure: Number of Deaths by Time (≤30 or >30 Days) From Last Study Drug Administration and by Primary Cause of Death
timeFrame: From date of first dose until death due to any cause (up to approximately 5 years)
measure: 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)
timeFrame: From the first dose until 30 days after the last dose of study treatment (up to approximately 5 years)
measure: Number of Participants With at Least One Treatment-Emergent Serious Adverse Event (SAE) by Highest Grade of Severity, According to NCI-CTCAE v4.0
timeFrame: From the first dose until 30 days after the last dose of study treatment (up to approximately 5 years)
measure: 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
timeFrame: From the first dose until 30 days after the last dose of study treatment (up to approximately 5 years)
measure: 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
timeFrame: From the first dose until 30 days after the last dose of study treatment (up to approximately 5 years)
measure: Number of Participants With at Least One TEAE Leading to Trastuzumab Dose Modification by Highest Grade of Severity According to NCI-CTCAE v4.0
timeFrame: From the first dose until 30 days after the last dose of study treatment (up to approximately 5 years)
measure: Percentage of Participants With at Least One TEAE of Special Interest by Highest Grade of Severity, According to NCI-CTCAE v4.0
timeFrame: From the first dose until 30 days after the last dose of study treatment (up to approximately 5 years)
measure: Median Left Ventricular Ejection Fraction (LVEF) Values Over Time
timeFrame: 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)
measure: Number of Participants by Investigator Interpretation of Left Ventricular Ejection Fraction (LVEF) Assessments Over Time
timeFrame: 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)
measure: Number of Participants With NCI-CTCAE v4.0 Grades 3 and 4 Clinical Laboratory Abnormalities in Hematology Tests Over Time
timeFrame: Baseline, Weeks 18, 36, and 60 (up to approximately 5 years)
measure: Number of Participants With NCI-CTCAE v4.0 Grades 3 and 4 Clinical Laboratory Abnormalities in Blood Chemistry Tests Over Time
timeFrame: Weeks 6, 12, and 18, and Unscheduled Visits (up to approximately 5 years)
measure: Observed Trough Serum Concentrations (Cmin) of Pertuzumab at Specified Timepoints
timeFrame: Pre-dose (0-4 hours) on Day 1 of Weeks 1, 4, 10, and 16
measure: Maximum Serum Concentrations (Cmax) of Pertuzumab at Specified Timepoints
timeFrame: Post-infusion (0-30 minutes, infused over 60 minutes) on Day 1 of Week 1 and 16
measure: Observed Trough Serum Concentrations (Cmin) of Trastuzumab at Specified Timepoints
timeFrame: Pre-dose (0-4 hours) on Day 1 of Weeks 1, 4, 10, and 16
measure: Maximum Serum Concentrations (Cmax) of Trastuzumab at Specified Timepoints
timeFrame: Post-infusion (0-30 minutes, infused over 60 minutes) on Day 1 of Week 1 and 16
measure: Symptom Severity Scale Score Over Time, Assessed by Participant Reporting on the M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT) Questionnaire
timeFrame: Baseline, Weeks 6, 12, 20, 28, 40, 52, and 64
measure: Symptom Interference Scale Score Over Time, Assessed by Participant Reporting on the MDASI-BT Questionnaire
timeFrame: Baseline, Weeks 6, 12, 20, 28, 40, 52, and 64
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: Miami
country: United States
facility: University of Miami Hospital & Clinics
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Inst.
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland Medical Center; Department of Neurology
state: Maryland
city: Bethesda
country: United States
facility: Associates in Oncology-Hematology, PC
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Inst.
state: Massachusetts
city: Saint Paul
country: United States
facility: Allina Health System
state: Minnesota
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Columbus
country: United States
facility: Mid Ohio Oncology Hematology;ZangMeister Center (West)
state: Ohio
city: Philadelphia
country: United States
facility: Temple Cancer Center; Oncology
state: Pennsylvania
city: Houston
country: United States
facility: Methodist Hospital Research Institute
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute; University of Utah
state: Utah
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Lin NU, Pegram M, Sahebjam S, Ibrahim N, Fung A, Cheng A, Nicholas A, Kirschbrown W, Kumthekar P. Pertuzumab Plus High-Dose Trastuzumab in Patients With Progressive Brain Metastases and HER2-Positive Metastatic Breast Cancer: Primary Analysis of a Phase II Study. J Clin Oncol. 2021 Aug 20;39(24):2667-2675. doi: 10.1200/JCO.20.02822. Epub 2021 May 4.