Trial Title:
Novel Neoadjuvant and Adjuvant Strategy for Germline BRCA 1/2 Mutated Triple Negative Breast Cancer
NCT ID:
NCT05485766
Condition:
Triple Negative Breast Neoplasms
Triple Negative Breast Cancer
Breast Neoplasms
Breast Cancer
BRCA1 Mutation
BRCA2 Mutation
BRCA Mutation
BRCA-Associated Breast Carcinoma
Conditions: Official terms:
Breast Neoplasms
Neoplasms
Triple Negative Breast Neoplasms
Paclitaxel
Carboplatin
Pembrolizumab
Olaparib
Conditions: Keywords:
BRCA1 protein
BRCA2 protein
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
200 mg fixed dose, IV, every 3 weeks (Q3W), on Days 1 of Cycles 1-4
Arm group label:
Pembrolizumab+ Paclitaxel + Carboplatin Followed by Pembrolizumab + Olaparib
Other name:
Keytruda
Other name:
MK-3475
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
80 mg/m2, IV, weekly, on Days 1, 8, 15 of Cycles 1-4
Arm group label:
Pembrolizumab+ Paclitaxel + Carboplatin Followed by Pembrolizumab + Olaparib
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Area under the curve (AUC 1.5), intravenously (IV), weekly, on Days 1, 8, 15 of Cycles
1-4
Arm group label:
Pembrolizumab+ Paclitaxel + Carboplatin Followed by Pembrolizumab + Olaparib
Intervention type:
Drug
Intervention name:
Olaparib
Description:
300 mg BID (twice daily) orally
Arm group label:
Pembrolizumab+ Paclitaxel + Carboplatin Followed by Pembrolizumab + Olaparib
Other name:
Lynparza
Intervention type:
Procedure
Intervention name:
Definitive Surgery
Description:
Each subject will undergo definitive surgery 3-6 weeks after conclusion of the last cycle
of the neoadjuvant treatment.
Arm group label:
Pembrolizumab+ Paclitaxel + Carboplatin Followed by Pembrolizumab + Olaparib
Summary:
This is a Phase II, single-arm, open label study to evaluate Olaparib plus Pembrolizumab
following platinum-based chemotherapy plus Pembrolizumab as neoadjuvant therapy for
germline BRCA (gBRCA) 1/2 mutated triple negative breast cancer (TNBC).
Pembrolizumab in combination with weekly paclitaxel and carboplatin (treatment 1) is
followed by Pembrolizumab in combination with Olaparib (treatment 2) in neoadjuvant
setting and Pembrolizumab in combination with Olaparib in adjuvant setting will be
studied
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Male/female subjects who are at least 18 years of age on the day of signing informed
consent with histologically confirmed diagnosis of invasive breast cancer
- Have histologically confirmed TNBC, as defined by the most recent ASCO/CAP
guidelines.
- Confirmed germline BRCA 1/2 mutated.
- Have previously untreated locally advanced non-metastatic (M0) TNBC defined as the
following combined primary tumor (T) and regional lymph node (N) staging per AJCC
for breast cancer staging criteria version 7 as assessed by the investigator based
on radiological and/or clinical assessment:
1. T1c, N1-N2
2. T2, N0-N2
3. T3, N0-N2
4. T4a-d, N0-N2
- It has been confirmed that there is no distant metastasis to each organ by the
following tests. Chest: Contrast CT or FDG-PET/CT Abdominal: Contract CT* or
FDG-PET/CT Bone: Bone scintigraphy or FDG-PET/CT Brain: In the case of no central
nervous system symptoms, examination for brain metastasis is not required.
- The subject (or legally acceptable representative if applicable) provides written
informed consent for the trial.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Have adequate organ function as defined in the protocol. Specimens must be collected
within 10 days prior to the start of study treatment.
Exclusion Criteria:
- Subjects who has a positive urine pregnancy test within 72 hours prior to
registration
- Has diagnosed as inflammatory breast cancer.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor .
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the
first dose of study drug.
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose
of study intervention.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
or any other form of immunosuppressive therapy within 7 days prior to the first dose
of study drug.
- Has a history of a second malignancy, unless potentially curative treatment has been
completed with no evidence of malignancy for 2 years.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and investigational drugs
used in this study and/or any of their excipients.
- Has active autoimmune disease that has required systemic treatment in the past 2
years
- Has a history of (non-infectious) pneumonitis/interstitial lung disease .
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV) infection.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HbsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has a history or current evidence of any condition, therapy, or laboratory
abnormality.
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children.
- Has had an allogenic tissue/solid organ transplant.
- Has received pre-treatment with Olaparib or other PARP inhibitors.
- Has significant cardiovascular disease
- Has a resting electrocardiogram (ECG) indicating uncontrolled, potentially
reversible cardiac conditions.
- Subject has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with
features suggestive of MDS/AML.
- Subject received colony-stimulating factors within 28 days prior to the first dose
of study intervention.
- Subject is considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection.
- Is either unable to swallow orally administered medication or has a gastrointestinal
disorder affecting absorption.
- Is, in the judgement of the investigator, unlikely to comply with the study
procedures, restrictions, and requirements of the study.
- Is currently receiving either strong or moderate inhibitors of cytochrome P450
(CYP)3A4 that cannot be discontinued for the duration of the study.
- Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be
discontinued for the duration of the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Aichi Cancer Center
Address:
City:
Nagoya
Country:
Japan
Status:
Not yet recruiting
Contact:
Last name:
Masaya Hattori, MD., PhD.
Facility:
Name:
Okayama University Hospital
Address:
City:
Okayama
Country:
Japan
Status:
Recruiting
Contact:
Last name:
Yuko Takahashi, MD., PhD.
Facility:
Name:
St. Luke's International Hospital
Address:
City:
Tokyo
Country:
Japan
Status:
Recruiting
Contact:
Last name:
Kumiko Kida, MD., PhD.
Start date:
February 29, 2024
Completion date:
September 30, 2027
Lead sponsor:
Agency:
Okayama University
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Okayama University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05485766
