Actively Recruiting
Study of Stereotactic Radiosurgery With Olaparib Followed by Durvalumab and Physician's Choice Systemic Therapy in Subjects With Breast Cancer Brain Metastases
Led by Colette Shen · Updated on 2025-12-23
41
Participants Needed
7
Research Sites
242 weeks
Total Duration
On this page
Sponsors
C
Colette Shen
Lead Sponsor
A
AstraZeneca
Collaborating Sponsor
AI-Summary
What this Trial Is About
This study is a Phase I/II study evaluating the safety and effectiveness of focused radiation therapy (radiosurgery) together with olaparib, followed by immunotherapy, for patients with brain metastases from triple negative or BRCA-mutated breast cancers. This study will have a Phase I portion in which subjects will be enrolled based on 3+3 dose escalation rules. Three dose levels of olaparib will be studied. Cycle 1 of study treatment will consist of Olaparib given twice daily concurrently with stereotactic radiosurgery (SRS). Olaparib will start one week prior to SRS and continue during and following SRS (1-5 fractions) for up to 28 days total. The number of doses of Olaparib will be dependent on how long it takes a subject to recover from SRS (ideally the subject will be off steroids, if they are required, at the start of Cycle 2, with exceptions outlined later in this section). Once the subject has recovered from SRS (based on investigator discretion) that will be considered the DLT period. Cycle 2 will be initiated with physician's choice systemic therapy and durvalumab. Cycle 2+ will equal 21 days. During Cycles 2 and 3, physician's choice systemic monotherapy will be given along with durvalumab per protocol. Each cycle will last 21 days. Imaging to evaluate intracranial and extracranial disease will be performed after Cycle 3, and subjects with response will continue with the systemic therapy and durvalumab until progression (intracranial or extracranial), unacceptable toxicity or death.
CONDITIONS
Official Title
Study of Stereotactic Radiosurgery With Olaparib Followed by Durvalumab and Physician's Choice Systemic Therapy in Subjects With Breast Cancer Brain Metastases
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Able and willing to provide written informed consent and HIPAA authorization
- Histologically confirmed breast cancer meeting criteria: triple negative or HER2-negative with BRCA mutation
- New brain metastasis by MRI planned for stereotactic radiosurgery (up to 15 untreated metastases, at least one >5mm)
- May have extracranial metastatic disease without signs of impending visceral crisis
- Prior systemic therapy allowed except prior combined PARP inhibitor and immune checkpoint inhibitor
- ECOG performance status 0-2 within 28 days before registration
- Body weight greater than 30 kg
- Life expectancy greater than 16 weeks
- Age 18 years or older at consent
- Completed prior systemic cancer treatment at least 7 days before study treatment and recovered from toxic effects
- Willing to provide blood and tissue samples for research
- Normal organ and bone marrow function within 28 days prior to treatment
- Female participants must be postmenopausal or have negative pregnancy test and use contraception if of childbearing potential
- Male participants must agree to use contraception or abstain from heterosexual activity during and 3 months post treatment
- Ability to understand and comply with study procedures
- Other inclusion criteria as specified by drug manufacturer and disease status
You will not qualify if you...
- Evidence of diffuse symptomatic leptomeningeal carcinomatosis
- Symptomatic brain metastases requiring immediate surgical resection within 1 week
- Intracranial hemorrhage or signs of impending herniation
- Prior whole brain radiation therapy
- Prior extracranial radiation therapy within 3 weeks unless palliative
- Signs of impending visceral crisis
- History of severe brain injury
- Last anticancer therapy dose within 7 days before study drug
- Myelodysplastic syndrome or acute myeloid leukemia
- Uncontrolled or serious cardiac conditions
- Grade 3 or 4 anemia, neutropenia or thrombocytopenia lasting more than 4 weeks related to recent chemotherapy
- History of interstitial lung disease
- Primary immunodeficiency
- Use of colony stimulating factors within 4 weeks prior to study therapy
- Immunocompromised or HIV positive without stable treatment
- Pregnant or breastfeeding
- Inability to undergo sequential MRI or CT evaluations
- Spinal cord compression without definitive treatment and stable disease
- Unable to swallow oral medication or gastrointestinal disorders affecting absorption
- Concurrent use of strong or moderate CYP3A inhibitors or inducers without required washout
- Previous allogenic bone marrow or double umbilical cord blood transplantation
- Participation in another clinical trial with investigational product in last 4 weeks
- Unresolved toxicity Grade 2 or higher from prior anticancer therapy except alopecia or vitiligo
- Radiotherapy involving over 30% bone marrow or wide field radiation within 4 weeks
- Major surgery within 28 days prior to first dose except brain metastasis resection for palliation
- Active or prior autoimmune or inflammatory disorders except specified exceptions
- Uncontrolled intercurrent illness or serious medical conditions limiting compliance
- History of other primary malignancy within 5 years except specified exceptions
- Recent or ongoing use of immunosuppressive medications except certain steroids
- Receipt of live attenuated vaccine within 30 days prior to first dose
- Known allergy or hypersensitivity to study drugs or excipients
- Prior treatment with durvalumab clinical study
- Prior severe immune-related adverse events from anti-PD-1, anti-PD-L1, or anti CTLA-4 therapy
- Clinically significant acute infection including tuberculosis, hepatitis B or C, or HIV without stable control
AI-Screening
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Trial Site Locations
Total: 7 locations
1
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
Actively Recruiting
2
Memorial Healthcare System
Hollywood, Florida, United States, 33028
Actively Recruiting
3
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, United States, 46202
Actively Recruiting
4
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
5
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27899
Actively Recruiting
6
Duke Cancer Institute
Durham, North Carolina, United States, 27710
Actively Recruiting
7
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Actively Recruiting
Research Team
C
Colette Shen, M.D., Ph.D.
CONTACT
A
Allison Lipps
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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