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
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)
1 other identifier
interventional
40
1 country
16
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Dec 2015
Longer than P75 for phase_2
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 10, 2015
CompletedFirst Posted
Study publicly available on registry
August 31, 2015
CompletedStudy Start
First participant enrolled
December 16, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2019
CompletedResults Posted
Study results publicly available
March 27, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
December 29, 2020
CompletedDecember 7, 2021
December 1, 2021
3.4 years
August 10, 2015
February 13, 2020
December 3, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Objective Response in the CNS, Assessed Using Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) Criteria
Responses were assessed by the investigator, based on magnetic resonance imaging (MRI) of the brain, physical examinations, routine neurological examinations, and corticosteroid dosing. An objective response in the central nervous system (CNS) was a complete response (CR) or partial response (PR) confirmed by repeat assessment, according to RANO-BM criteria. A CR was defined as the disappearance of all CNS target lesions sustained for at least 4 weeks; no new lesions; no corticosteroids; and stable or improved clinically; for non-target lesions, a CR was the disappearance of all enhancing CNS non-target lesions and no new CNS lesions. A PR was defined as at least a 30% decrease in the sum longest diameter (LD) of CNS target lesions, taking as reference the baseline sum LD sustained for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; and stable or improved clinically. The 95% Clopper-Pearson exact confidence intervals were calculated for responses.
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 (26)
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)
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 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)
- +21 more secondary outcomes
Study Arms (1)
Pertuzumab + Trastuzumab
EXPERIMENTALParticipants 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.
Interventions
Participants will receive 840 milligrams (mg) loading dose of pertuzumab, followed every 3 weeks thereafter by a dose of 420 mg via intravenous (IV) infusion until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
Participants will receive trastuzumab at a dose of 6 milligrams per kilogram (mg/kg) of body weight once weekly via IV infusion until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genentech, Inc.lead
Study Sites (16)
Arizona Cancer Center
Tucson, Arizona, 85719, United States
City of Hope National Medical Center
Duarte, California, 91010, United States
Stanford Cancer Institute
Stanford, California, 94305, United States
University of Miami Hospital & Clinics
Miami, Florida, 33136, United States
H. Lee Moffitt Cancer Center and Research Inst.
Tampa, Florida, 33612, United States
Northwestern University
Chicago, Illinois, 60611-2987, United States
University of Maryland Medical Center; Department of Neurology
Baltimore, Maryland, 21201, United States
Associates in Oncology-Hematology, PC
Bethesda, Maryland, 20817, United States
Dana Farber Cancer Inst.
Boston, Massachusetts, 02115, United States
Allina Health System
Saint Paul, Minnesota, 55102, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
Mid Ohio Oncology Hematology;ZangMeister Center (West)
Columbus, Ohio, 43213, United States
Temple Cancer Center; Oncology
Philadelphia, Pennsylvania, 19140, United States
Methodist Hospital Research Institute
Houston, Texas, 77030, United States
Huntsman Cancer Institute; University of Utah
Salt Lake City, Utah, 84112, United States
Northwest Medical Specialties, PLLC
Tacoma, Washington, 98405, United States
Related Publications (1)
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.
PMID: 33945296DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Genentech, Inc.
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 10, 2015
First Posted
August 31, 2015
Study Start
December 16, 2015
Primary Completion
May 1, 2019
Study Completion
December 29, 2020
Last Updated
December 7, 2021
Results First Posted
March 27, 2020
Record last verified: 2021-12