None listed
Conditions
Interventions
Drug : Twice daily oral Olaparib 300mg alone for Olaparib alone arm or Twice daily oral Olaparib plus intravenous Durvalumab every 4 weeks for Olaparib plus Durvalumab as maintenance therapy until dis
Sponsors
Asan Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Age= 21years of age 2.ECOG(Eastern Cooperative Oncology Group) performance status 0-2 3.Inoperable locally advanced or metastatic breast cancer not amenable to resection with curative intent and histologically confirmed to be estrogen receptor(ER) negative, progesterone receptor(PR) negative, and HER2 negative : - ER(estrogen receptor) negative status is defined as 10% of invasive tumour cells, or - IHC 0, as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within =10% of the invasive tumour cells, or - FISH(Fluorescent In Situ hybridization) negative based on: - single-probe average HER2 copy number 3 x 10^9/L. 8.Platelet count >100 x 10^9/L. 9.Total bilirubin 51 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance. 13.For subjects of childbearing potential, agreement (by both subject and partner) to use an effective form of contraception, including surgical sterilization, reliable barrier method, birth control pills, contraceptive hormone implants, or true abstinence and to continue its use for the duration of the study and for 6 months after last dose of study treatment. 14.Subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 15.Subjects willing and able to comply with the
Exclusion criteria
Exclusion criteria: 1.Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of first dose of treatment. Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks since last dose of the previous investigational agent of device. 2.Concurrent enrolment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study. 3.Active autoimmune disease that has required systemic treatment in 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, or similar treatment) is not considered a form of systemic treatment. 4.Current or prior use of immunosuppressive medication within 28 days before the first dose of investigational drug(s), with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid. 5.Previous treatment with PARP inhibitors including olaparib. 6.Patients that have required discontinuation of treatment due to treatment-related toxicities from prior therapy with PD-1, PDL-1 or CTLA-4 inhibitors or previous history of immune-related grade 3 or 4 adverse event. 7.Known active central nervous system metastasis and / or carcinomatous meningitis. Subjects with previously treated brain metastases may participate, provided they have: A.Stable brain metastases [without evidence of progression by imaging (confirmed by computerized tomography {CT} scan if CT used at prior imaging) for at least four weeks prior to the first dose of trial treatment**, B.No evidence of new or enlarging brain metastases; any neurologic symptoms should have returned to baseline, C.Not used steroids for brain metastases in the 28 days prior to trial initiation. **This exception does not include carcinomatous meningitis, as subjects with carcinomatous meningitis are excluded regardless of clinical stability. 8.History and/or confirmed pneumonitis, or extensive bilateral lung disease on high resolution/spiral CT scan. Patients with suspected or confirmed myelodysplastic syndrome/acute myeloid leukemia. 9.History of another primary malignancy except for: A.Malignancy treated with curative intent and with no known active disease =5 years before the first dose of study drug and of low potential risk for recurrence. B.Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. C.Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ. 10.Major surgery within 2 weeks of starting the study, and subjects must have recovered from any effects of any major surgery. 11.Receipt of radiation therapy within 4 weeks prior to starting study drug(s). Limited field of radiation for palliation within 2 weeks of the first dose of study treatment is allowed provided: A.The lung is not in the radiation field B.Irradiated lesion(s) cannot be used as target lesions 12.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, card
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the efficacy as assessed by PFS(progression free survival) of maintenance olaparib or olaparib in combination with durvalumab following clinical benefit (complete response [CR], partial response [PR] or stable disease [SD]) with platinum based chemotherapy in the 1st or 2nd line setting for treatment of metastatic triple negative breast cancer (mTNBC). | — |
Secondary
| Measure | Time frame |
|---|---|
| Determine safety and tolerability as determined by adverse events of maintenance olaparib plus durvalumab;To determine the efficacy of maintenance olaparib following platinum-based chemotherapy as assessed by overall response rate (ORR).;Determine safety and tolerability as determined by adverse events of maintenance olaparib alone;To determine the efficacy of maintenance olaparib in combination with durvalumab following platinum-based chemotherapy as assessed by overall response rate (ORR).;To determine the efficacy of maintenance olaparib following platinum based chemotherapy as assessed by overall survival (OS).;To determine the efficacy of maintenance olaparib in combination with durvalumab following platinum based chemotherapy as assessed by overall survival (OS). | — |
Countries
Korea, Republic of
Contacts
Public ContactDalnim Seo
Asan Medical Center
Outcome results
None listed