Brief Title
Niraparib in Combination With Pembrolizumab in Patients With Triple-negative Breast Cancer or Ovarian Cancer
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
Brief Summary
This Phase 1/2 study will evaluate the safety and efficacy of combination treatment with
niraparib and pembrolizumab (MK-3475) in patients with advanced or metastatic triple-negative
breast cancer or recurrent ovarian cancer. (KEYNOTE-162)
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Phase 1: Number of Subjects Reporting Dose-Limiting Toxicities (DLTs)
Secondary Outcome
To Evaluate the Safety and Tolerability of Combination Treatment With Niraparib and Pembrolizumab Using Common Terminology Criteria for Adverse Events (CTCAE, v4.03)
Condition
Triple Negative Breast Cancer
Intervention
niraparib
Study Arms / Comparison Groups
niraparib plus pembrolizumab
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
122
Start Date
March 2016
Completion Date
March 2020
Primary Completion Date
May 2018
Eligibility Criteria
Main Inclusion Criteria:
- Patient has histologically proven advanced (unresectable) or metastatic cancer as
outlined below according to study phase and disease type:
1. Phase 1 patients (breast or ovarian cancer)
- Patients with advanced or metastatic breast cancer must have disease that is
HER2-negative, estrogen receptor-negative, and progesterone
receptor-negative (ie, TNBC). Patients with advanced or metastatic disease
may have up to 4 lines of cytotoxic therapy. Neoadjuvant and adjuvant
therapies are not counted towards lines of therapy.
- Patients must have any epithelial (ie, serous, endometroid, mucinous, clear
cell) ovarian, fallopian tube, or primary peritoneal cancer. Patients must
have experienced a response lasting at least 6 months to first-line
platinum-based therapy but currently considered to have platinum-resistant
disease per investigator's assessment (e.g, patient is not eligible for
further platinum containing treatment). Patients may have received up to 5
lines of cytotoxic therapy for advanced or metastatic cancer. Neoadjuvant
and adjuvant therapies are not counted towards lines of therapy.
2. Phase 2 patients (breast or ovarian cancer)
- Patients with advanced or metastatic breast cancer must have TNBC. Patients
with advanced or metastatic disease may have received up to 2 lines of
cytotoxic therapy. Adjuvant and/or neoadjuvant therapies are not counted in
the number of lines of therapy. TNBC patients who have previously received
platinum chemotherapy in the metastatic setting are allowed to enroll in the
study as long as they did not progress while on or within 8 weeks from the
day of the last platinum administration.
- Patients must have with high-grade serous or endometroid ovarian, fallopian
tube, or primary peritoneal cancer. Patients must have experienced a
response lasting at least 6 months to first-line platinum-based therapy but
currently considered to have platinum-resistant disease per investigator's
assessment (e.g, patient is not eligible for further platinum containing
treatment). Patients may have had up to 4 lines of cytotoxic therapy for
advanced or metastatic cancer. Neoadjuvant, adjuvant, and the combination of
both will be considered as one line of therapy.
- Archival tumor tissue available or a fresh biopsy must be obtained prior to study
treatment initiation
- Measurable lesions by RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) 0 or 1
- Adequate organ function
- Able to take oral medications
- Female patient, if of childbearing potential, has a negative serum pregnancy test
within 72 hours of taking study medication and agrees to abstain from activities that
could result in pregnancy from enrollment through 120 days after the last dose of
study treatment
- Male patient agrees to use an adequate method of contraception
Main Exclusion Criteria:
- Patients with primary platinum refractory ovarian cancer (ie, progressive disease on
or within 6 months of first-line platinum therapy)
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Note: Patients previously treated for brain metastases may be able to participate
provided they are stable
- Patient has a known additional malignancy that progressed or required active treatment
within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous
cell carcinoma of the skin that has undergone potentially curative therapy, or in situ
cervical cancer
- Poor medical risk
- Condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or
laboratory abnormality that might confound the study results, or interfere with the
patient's participation for the full duration of the study treatment.
- Pregnant or breastfeeding, or expecting to conceive children within the projected
duration of the study
- Immunodeficiency or is receiving systemic steroid therapy or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study treatment
- Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Known active hepatitis B or hepatitis C
- Active autoimmune disease that has required systemic treatment in the past 2 years
(ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive
drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment
- Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Prior treatment with a known poly(ADP-ribose) polymerase (PARP) inhibitor
- Heart-rate corrected QT interval (QTc) prolongation > 470 msec at screening
- Known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid
leukemia (AML)
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Bruce Dezube, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02657889
Organization ID
3000-PN162-01-001
Responsible Party
Sponsor
Study Sponsor
Tesaro, Inc.
Collaborators
Merck Sharp & Dohme Corp.
Study Sponsor
Bruce Dezube, MD, Study Director, Tesaro, Inc.
Verification Date
February 2020