Phase II Multicenter Study of Durvalumab and Olaparib in Platinum tReated Advanced Triple Negative Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Olaparib Oral Product
- Conditions
- Triple Negative Breast Cancer
- Sponsor
- Duke University
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- Efficacy of Olaparib Alone as Assessed by PFS (Progression-free Survival) Reported as Events Per Month
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a randomized, international, multicenter, Phase II study designed to explore the efficacy of olaparib or olaparib in combination with durvalumab in platinum-treated mTNBC. The primary objectives are to explore olaparib or olaparib in combination with durvalumab as maintenance therapy following clinical benefit with platinum-based therapy in subjects with mTNBC.
Detailed Description
Subjects suitable for enrollment into this trial are adult subjects with histologically documented triple negative adenocarcinoma of the breast that is inoperable, locally advanced, or metastatic, and is not amenable to resection with curative intent, and who have received at least 4 cycles of platinum-based chemotherapy in the 1st or 2nd line setting AND derived clinical benefit (CR / PR / SD) per RECIST 1.1 with platinum-based therapy as determined by the treating physician. Eligible subjects will be randomized to either olaparib or olaparib in combination with durvalumab. Study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Upon treatment discontinuation, subjects will be followed every 2 months for survival. Although randomization will be used to allocate subjects to either the olaparib or olaparib in combination with durvalumab arm, no comparisons between treatment regimens are planned. The purpose of randomization was to reduce bias due to subject selection into either treatment arm.
Investigators
Sarah Sammons, MD
Assistant Professor of Medicine
Duke University
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 21 years of age
- •ECOG performance status 0-2
- •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 negative status is defined as \< 1% tumor cells positive for ER by immunohistochemistry (IHC), irrespective of staining intensity
- •PR negative status is defined as \< 1% tumor cells positive for PR by IHC, irrespective of staining intensity
- •NOTE: Enrollment is permitted for ER/PR low-expression subjects (defined as ≤ 10%) who are expected to benefit from this trial at the investigator's discretion.
- •HER2 negative status is determined by:
- •IHC 1+, as defined by incomplete membrane staining that is faint/barely perceptible and within \> 10% of invasive tumor 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 tumor cells, or
- •FISH negative based on:
Exclusion Criteria
- •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 or device.
- •Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study.
- •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.
- •Is taking chronic systemic steroids in doses \> 10mg of prednisolone or equivalent within 7 days prior to the first dose of trial treatment.
- •Previous treatment with PARP inhibitors including olaparib.
- •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.
- •Known active central nervous system metastasis and / or carcinomatous meningitis. Subjects with previously treated brain metastases may participate, provided they have:
- •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\*\*,
- •No evidence of new or enlarging brain metastases; any neurologic symptoms should have returned to baseline,
- •Not used steroids for brain metastases in the 7 days prior to trial initiation. Taking chronic systemic steroids in doses ≤ 10mg of prednisolone is allowed.
Arms & Interventions
A - olaparib alone
Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Intervention: Olaparib Oral Product
B - olaparib plus durvalumab
Twice daily oral olaparib plus intravenous Durvalumab every 4 weeks as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Intervention: Olaparib Oral Product in combination with Durvalumab
Outcomes
Primary Outcomes
Efficacy of Olaparib Alone as Assessed by PFS (Progression-free Survival) Reported as Events Per Month
Time Frame: From date of randomization until the date of documented progression or date of death, whichever came first, approximately 1 year.
PFS, defined as the time from randomization to the first occurrence of disease progression or death from any cause on study for olaparib alone. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Death on study is defined as death from any cause within 30 days of the last dose of study treatment regimen. Reported as events (disease progression or death) per month.
Efficacy of Olaparib in Combination With Durvalumab as Assessed by PFS (Progression-free Survival)
Time Frame: From date of randomization until the date of documented progression or date of death, whichever came first, approximately 1 year.
PFS, as defined as the time from randomization to the first occurrence of disease progression (as determined using RECIST v1.1 criteria and assessed by the investigator) or death from any cause on study for olaparib in combination with durvalumab. Death on study is defined as death from any cause within 30 days of the last dose of study treatment regimen. Reported as (disease progression or death) events per month.
Secondary Outcomes
- Overall Survival (Olaparib in Combination With Durvalumab)(From date of randomization until death or last patient contact, approximately 2 years)
- Overall Survival (Olaparib Alone)(From date of randomization until death or last patient contact, approximately 2 years)
- Clinical Benefit Rate (CBR) as Measured by the Number of Participants Achieving Complete Response (CR), Partial Response (PR) or Stable Disease for ≥ 24 Weeks (SD) as Defined by RECIST 1.1. (Olaparib in Combination With Durvalumab)(Assessed every 8 weeks from date of randomization until documented disease progression or last patient contact, approximately 1 year)
- Overall Response Rate (ORR) as Measured by Number of Participants Achieving Complete Response (CR) or Partial Response (PR) as Defined by RECIST 1.1 (Olaparib Alone)(Assessed every 8 weeks from date of randomization until documented disease progression or last patient contact, approximately 1 year)
- Overall Response Rate (ORR) as Measured by Number of Participants Achieving Complete Response (CR) or Partial Response (PR) as Defined by RECIST 1.1 (Olaparib in Combination With Durvalumab)(Assessed every 8 weeks from date of randomization until documented disease progression or last patient contact, approximately 1 year)
- Clinical Benefit Rate (CBR) as Measured by the Number of Participants Achieving Complete Response (CR), Partial Response (PR) or Stable Disease for ≥ 24 Weeks (SD) as Defined by RECIST 1.1. (Olaparib Alone)(Assessed every 8 weeks from date of randomization until documented disease progression or last patient contact, approximately 1 year)