Niraparib in Combination With Pembrolizumab in Patients With Triple-negative Breast Cancer or Ovarian Cancer (TOPACIO)
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|ClinicalTrials.gov Identifier: NCT02657889|
Recruitment Status : Active, not recruiting
First Posted : January 18, 2016
Results First Posted : February 11, 2020
Last Update Posted : February 11, 2020
|Condition or disease||Intervention/treatment||Phase|
|Triple Negative Breast Cancer Ovarian Cancer Breast Cancer Metastatic Breast Cancer Advanced Breast Cancer Stage IV Breast Cancer Fallopian Tube Cancer Peritoneal Cancer||Drug: niraparib Biological: pembrolizumab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||122 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1/2 Clinical Study of Niraparib in Combination With Pembrolizumab (MK-3475) in Patients With Advanced or Metastatic Triple-Negative Breast Cancer and in Patients With Recurrent Ovarian Cancer|
|Study Start Date :||March 2016|
|Actual Primary Completion Date :||May 2018|
|Estimated Study Completion Date :||March 2020|
Experimental: niraparib plus pembrolizumab
Phase 1: Dose-escalation: ascending doses of niraparib up to 300mg/day orally (PO) on Days 1-21 and pembrolizumab 200mg intravenously (IV) on Day 1 of each 21-day cycle
Phase 2: niraparib (recommended Phase 2 dose) in combination with pembrolizumab 200mg IV on Day 1 of each 21-day cycle
- Phase 1: Number of Subjects Reporting Dose-Limiting Toxicities (DLTs) [ Time Frame: During Cycle 1, ie, during the first 21 days of treatment ]
DLTs are defined as:
Any treatment-related Grade ≥ 3 non-hematologic clinical (non-laboratory) AE
Any treatment-related Grade 3 or Grade 4 non-hematologic lab abnormality if:
- Medical intervention is required to treat the patient, or
- The abnormality leads to hospitalization, or
- The abnormality persists for ≥ 7 days.
Any treatment-related hematologic toxicity specifically defined as:
- Thrombocytopenia Grade 4 for ≥ 7 days, or Grade 3 or 4 associated with bleeding or requiring platelet transfusion;
- Neutropenia Grade 4 for ≥ 7 days, or Grade 3 or 4 associated with infection or febrile neutropenia;
- Anemia Grade 4, or Grade 3 or 4 requiring blood transfusion.
Any treatment-related AE leading to niraparib dose interruption per the following criteria:
- A dose interruption for a non-DLT lab abnormality lasting ≥ 14 days.
- A dose in interruption per dose modification rules for nonhematologic AE leading to < 80% of an intended dose being administered.
- Phase 2: Objective Response Rate (ORR) [ Time Frame: Up to 40 weeks ]ORR is defined as the percentage of patients who achieved a best overall response of Complete Response (CR) or Partial Response (PR), per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions as assessed by the Investigator: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
- To Evaluate the Safety and Tolerability of Combination Treatment With Niraparib and Pembrolizumab Using Common Terminology Criteria for Adverse Events (CTCAE, v4.03) [ Time Frame: AEs were collected up to 90 days following the last dose of study treatment, where the median duration of treatment was 3 months. ]Percentage of patients with at least 1 Treatment-Emergent Adverse Event. Refer to the adverse event tables for specific details.
- Phase 2: Overall Response Rate (ORR) as Measured by Immune-related RECIST (irRECIST) [ Time Frame: Radiographic evaluations were conducted every 9 weeks while on study treatment (every 12 weeks after 1 year of scans) independent of cycle delays and/or dose interruptions, and/or at any time when progression of disease is suspected. ]ORR by irRECIST is defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR) using immune-related RECIST criteria.
- Phase 2: Duration of Response (DOR) [ Time Frame: From first documentation of response (CR or PR) using RECIST (v1.1) as assessed by the Investigator until time of first documented progression. ]From first documentation of response (CR or PR) using RECIST (v1.1) as assessed by the investigator until time of first documented progression or death by any cause. No maximum timeframe was specified in the protocol.
- Phase 2: Disease Control Rate (DCR) [ Time Frame: Up to 40 weeks ]DCR is defined as the percentage of patients who achieved a CR or PR or stable disease (SD) using RECIST (v1.1) as assessed by the Investigator.
- Phase 2: Progression Free Survival (PFS) [ Time Frame: From date of first dose to the earlier date of assessment of progression of death by any cause in the absence of progression. ]From date of first dose to the earlier date of assessment of progression or death by any cause in the absence of progression. No maximum timeframe was specified in the protocol.
- Phase 2: Overall Survival (OS) [ Time Frame: From date of first dose to the date of death by any cause. ]Patients were followed off treatment every 90 days for survival status. Overall survival is defined as the time from first dose to the date of death by any cause. No maximum timeframe was specified in the protocol.
- Phase 1 and Phase 2: To Evaluate the Pharmacokinetics (PK) of Niraparib and Associated Major Metabolite M1 During Combination Treatment. [ Time Frame: Approximately 9 months ]Area Under the Curve (AUC), Minimum Concentration (Cmin), Maximum Concentration (Cmax), Clearance After Oral Administration (CL/F), Volume of Distribution After Oral Administration (Vz/F), AUC at Steady State (AUCss), Cmin at Steady State (Cmin,ss), Cmax at Steady State (Cmax,ss).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02657889
|United States, Alabama|
|Birmingham, Alabama, United States, 35294|
|United States, Arizona|
|Scottsdale, Arizona, United States, 85258|
|Scottsdale, Arizona, United States, 85259|
|United States, California|
|Los Angeles, California, United States, 90048|
|San Francisco, California, United States, 94115|
|Stanford, California, United States, 94305|
|United States, District of Columbia|
|Washington, District of Columbia, United States, 20007|
|United States, Florida|
|Jacksonville, Florida, United States, 32224|
|Miami, Florida, United States, 33136|
|Orlando, Florida, United States, 32804|
|United States, Georgia|
|Atlanta, Georgia, United States, 30342|
|United States, Illinois|
|Chicago, Illinois, United States, 60637|
|United States, Louisiana|
|Covington, Louisiana, United States, 70433|
|United States, Massachusetts|
|Boston, Massachusetts, United States, 02111|
|Boston, Massachusetts, United States, 02215|
|Burlington, Massachusetts, United States, 01805|
|United States, Michigan|
|Detroit, Michigan, United States, 48201|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, New Jersey|
|Morristown, New Jersey, United States, 07960|
|United States, New York|
|Lake Success, New York, United States, 11042|
|New York, New York, United States, 10065|
|United States, North Carolina|
|Chapel Hill, North Carolina, United States, 27599|
|Charlotte, North Carolina, United States, 28204|
|United States, Ohio|
|Cleveland, Ohio, United States, 44106|
|United States, Oklahoma|
|Oklahoma City, Oklahoma, United States, 73104|
|United States, Tennessee|
|Memphis, Tennessee, United States, 38104|
|Nashville, Tennessee, United States, 37203|
|United States, Texas|
|San Antonio, Texas, United States, 78229|
|United States, Virginia|
|Charlottesville, Virginia, United States, 22908|
|United States, Washington|
|Seattle, Washington, United States, 98109|
|Study Director:||Bruce Dezube, MD||Tesaro, Inc.|