Trial design:
Phase II, prospective, multi-center, randomized, open label, parallel group study in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1/2 mutation, with 2:1 randomization into Arm A (olaparib + elacestrant) or arm B (olaparib). Treatment in either arm will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study.
Trial population:
Patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1/2 mutation, with an indication for standard-of-care PARP inhibitor therapy and planned treatment with olaparib, an ECOG performance status of 0-2 and life expectancy of \> 6 months, with normal bone marrow and kidney functions and no active or newly diagnosed central nervous system (CNS) metastases or symptomatic metastatic visceral disease at risk of life-threatening complications.
Interventions:
Patients randomized to Arm A will receive 600 mg olaparib daily and 400 mg elacestrant daily, while patients randomized to Arm B will receive 600 mg olaparib daily. Blood tests (hematology, biochemistry) will be performed at the beginning of every cycle, and imaging for tumor assessment (chest and abdominopelvic imaging) as well as QoL assessments will be performed every three months and in case of suspicion of progression/end of study.
Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for scheduled visit, the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
Female or male patients.
Age at study entry of at least 18 years.
Locally advanced or metastatic breast cancer that is HR-positive (ER and/or PgR ≥ 10% of stained cells at IHC) and HER2-negative (IHC 0 or 1+, or 2+ and ISH negative according to ASCO/CAP guidelines).
Known hypersensitivity reaction to one of the compounds, excipients, or substances used in this protocol.
Active or newly diagnosed CNS metastases, including leptomeningeal carcinomatosis, carcinomatous meningitis, or radiographic signs of CNS hemorrhage. Note: Patients with stable brain metastases are allowed. Radiotherapeutic treatment must be completed 1 week before planned day 1 of study therapy.
Presence of symptomatic metastatic visceral disease that are at risk of life-threatening complications in the short term, including but not confined to massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or fulminant liver involvement.
Hemoglobin < 9 g/dL (< 5.6 mmol/L)
Parallel
Olaparib + Elacestrant
DrugOlaparib 600 mg orally daily and elacestrant 400 mg orally daily
Olaparib
DrugOlaparib 600 mg orally daily
Progression free survival (PFS)
PFS, investigator-assessed. To evaluate the impact on PFS of elacestrant with olaparib compared to olaparib alone in patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1/2 mutations.
Time-to-treatment failure (TTF)
To compare TTF between treatment arms (i.e., elacestrant + olaparib vs. olaparib).
Overall survival (OS)
To compare OS between treatment arms.
Patient reported outcome (PRO) in the form of quality of life (QoL) assessment
To assess and compare patient reported breast cancer-specific QoL as measured by FACT-ES questionnaire.
PFS in stratified and exploratory subgroups
To compare PFS in the stratified subgroups: pre-treatment chemotherapy in the metastatic setting yes vs. no. To compare PFS in the exploratory subgroups specified in the protocol.
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GBG Forschungs GmbH
Lead sponsor
Stemline Therapeutics, Inc.
Collaborator
