Study of Stereotactic Radiosurgery With Olaparib Followed by Durvalumab and Physician's Choice Sy… (NCT04711824) | Clinical Trial Compass
Active — Not RecruitingPhase 1/2
Study of Stereotactic Radiosurgery With Olaparib Followed by Durvalumab and Physician's Choice Systemic Therapy in Subjects With Breast Cancer Brain Metastases
United States41 participantsStarted 2022-03-09
Plain-language summary
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.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Able and willing to provide written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
. Subject has histologically confirmed diagnosis of breast cancer per AJCC 8th edition meeting any of the following criteria: 1) triple negative, defined as ER/PR expression \<10% and HER2-negative, with any BRCA status; or 2) HER2-negative (with ER/PR expression \>=10% with germline or somatic BRCA mutation.
. Subject has diagnosis of new brain metastasis by MRI, with a plan to undergo stereotactic radiosurgery (SRS) (up to 15 untreated metastases and at least 1 metastasis with maximum dimension \> 5mm). Patients are permitted to have undergone recent craniotomy and resection of metastasis/metastases if at least 1 other intact metastasis or gross residual tumor planned for definitive SRS is present. Patients may have had prior SRS as long as the previously treated brain metastases are stable and not planned for additional therapy. Re-irradiation of a lesion previously treated with SRS is not allowed. Discrete dural lesions are allowed.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
. Subject may have other sites of extracranial metastatic disease (does not need to be stable, as long as no signs of impending visceral crisis).
. Subjects may have had prior systemic therapy other than combination DDR inhibitor (PARP inhibitor) and immune checkpoint inhibitor (i.e., prior PARP inhibitor without concurrent immune checkpoint inhibitor, or prior immune checkpoint inhibitor without concurrent PARP inhibitor, are allowed).
. Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0-2 within 28 days prior to registration.
. Body weight \>30 kg (for durvalumab monotherapy or durvalumab combination).
. Subject has life expectancy \> 16 weeks.
Exclusion criteria
. Subject has evidence of diffuse symptomatic leptomeningeal carcinomatosis.
. Subject has symptomatic brain metastases requiring immediate surgical resection within 1 week.
. Subject has evidence of intracranial hemorrhage or signs of impending herniation.
. Subject has had prior whole brain radiation therapy. Prior SRS to brain metastases is allowed as long as previously treated lesions are stable and not planned for further therapy.
. Subject has had prior extracranial radiation therapy within 3 weeks of study initiation unless palliative.
. Subject has signs of impending visceral crisis.
. Subject has a history of severe brain injury.
. Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤ 7 days prior to the first dose of study drug. If sufficient wash-out time has not occurred (defined as 5 half-lives for the prior anti-cancer therapy), a longer wash-out period will be required, as agreed by sponsor-investigator and the site investigator. Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable.