NCT04711824
Study of Stereotactic Radiosurgery With Olaparib Followed by Durvalumab and Physician's Choice Systemic Therapy in Subjects With Breast Cancer Brain Metastases
Active, Not Recruiting
PHASE1Ages 18+InterventionalTreatmentColette ShenInvestigator-initiated
~41 participants
Updated 2026-07-10 on ClinicalTrials.gov
What's tested:OlaparibStereotactic RadiosurgeryDurvalumabPhysicians Choice systemic chemotherapy
At a glance
Recruiting sites
0 of 7 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Frequency and severity of adverse events
Measured over 4 weeks
+1 more outcome measured
Conditions
Where it's being run
7 sites across 6 statesNorth Carolina2
Alabama1
Florida1
Indiana1
New York1
Ohio1
Study leadership
- Colette Shen, M.D., Ph.D · PRINCIPAL_INVESTIGATOR · University of North Carolina, Chapel Hill
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Platelets ≥100 x 109/L
Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
Hemoglobin (Hgb) ≥ 10 g/dL with no blood transfusion in the past 28 days
Calculated creatinine clearance ≥ 51 mL/min
Bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) ≤ 2.5 × ULN unless liver metastases are present in which case they must be ≤ 5x ULN
Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) Alanine aminotransferase (ALT) ≤ 2.5 × ULN unless liver metastases are present in which case, they must be ≤ 5x ULN
International Normalized Ratio (INR) or Prothrombin Time (PT)
Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN; Patients taking warfarin may participate in this study; however, it is recommended that INR be monitored carefully at least once per week for the first month, then monthly if the INR is stable. 13. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on Day 1. Postmenopausal is defined as:
Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50
Radiation-induced oophorectomy with last menses \> 1 year ago
Chemotherapy-induced menopause with \> 1-year interval since last menses
Surgical sterilisation (bilateral oophorectomy or hysterectomy) 14. Female patients of childbearing potential must be willing to abstain from heterosexual activity or to use 2 highly effective methods of contraception as described in the protocol from the time of informed consent until 3 months after treatment discontinuation. 15. Male patients must be willing to abstain from heterosexual activity or use a condom during treatment and for 3 months after treatment discontinuation. See the protocol for additional information. 16. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the sponsor-investigator.
Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the sponsor-investigator. 26. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. 27. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product (IP). NOTE: Resection of brain metastasis and local surgery of isolated lesions for palliative intent is acceptable. 28. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
Patients with vitiligo or alopecia
Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
Any chronic skin condition that does not require systemic therapy
Patients without active disease in the last 5 years may be included but only after consultation with the sponsor-investigator
Patients with celiac disease controlled by diet alone 29. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. 30. History of another primary malignancy except for:
Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence.
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
Adequately treated carcinoma in situ without evidence of disease. 31. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection).
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
Steroids used to treat edema from SRS as per protocol. 32. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP. 33. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 34. Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment. 35. Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4:
Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
Must not have experienced a ≥ Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤ Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day. 36. Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy including:
tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and TB testing in line with local practice),
hepatitis B (known positive HBV surface antigen (HBsAg) result),
hepatitis C, or
human immunodeficiency virus (positive HIV 1/2 antibodies).
What this trial measures
- Frequency and severity of adverse events4 weeks
Phase I: frequency and severity of adverse events will be measured using common toxicity criteria for adverse events version 5.
- Intracranial Disease control rate6 months
Phase II: Intracranial disease control rate will be defined as the percentage of subjects with \[complete response (CR) + partial response (PR) + stable disease\] per RANO-BM criteria at 6 months after study treatment initiation.