ELACESTRANT DIHYDROCHLORIDE for Breast cancer (hormone receptor-positive, HER2-negative) with gBRCA1/2 mutations (locally advanced or metastatic)

Stratification factors

• Pre-treatment chemotherapy in the metastatic setting (yes vs. no)

Inclusion criteria

• {"criterion_text":"- 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.\n- Life-expectancy > 6 months.\n- For female patients: patients of childbearing potential (defined as not post-menopausal and not permanently sterile [latter defined as having undergone hysterectomy, bilateral salpingectomy, or bilateral oophorectomy]) require a negative serum or urinary pregnancy test within 72 hours before starting treatment in this study (in this case, patients need to use highly effective non-hormonal contraceptive methods as specified in the protocol). For male patients: during the intervention period and for at least 120 days after the last dose of elacestrant, patients should refrain from heterosexual intercourse or use a condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak), and they should refrain from donating sperm.\n- Female or male patients.\n- Age at study entry of at least 18 years.\n- Centrally confirmed 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).\n- Patients with deleterious or suspected deleterious gBRCA1/2 detected upon local testing.\n- Willingness and ability to provide archived formalin fixed paraffin embedded tissue (FFPE) block or a partial block from archived tumor or metastasis.\n- Indication for standard-of-care PARP inhibitor therapy and planned treatment with olaparib.\n- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.\n- Resolution of all acute toxic effects of prior anti-cancer therapy including endocrine therapy or surgical procedures to NCI CTCAE version 5.0 grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator’s discretion)."}

Exclusion criteria

• {"criterion_text":"- Known hypersensitivity reaction to one of the compounds, excipients, or substances used in this protocol.\n- Active and current anticoagulation for treatment purposes of thrombotic events occurring < 6 months before enrolment is not allowed (prophylactic anticoagulation, however, is acceptable). Treatment with an anticoagulant for a thrombotic event occurring > 6 months before enrolment, or for an otherwise stable and allowed medical condition (e.g., well controlled atrial fibrillation) is acceptable, provided dose and coagulation parameters (as defined by local standard of care) are stable for at least 28 days prior to the first dose of study drug.\n- Known difficulty in tolerating oral medications or conditions which would impair absorption of oral medications such as: uncontrolled nausea or vomiting (i.e., CTCAE ≥ grade 3 despite antiemetic therapy), ongoing gastrointestinal obstruction/motility disorder, malabsorption syndrome, or prior gastric bypass.\n- History of endometrial intraepithelial neoplasia in patients who have not undergone a hysterectomy.\n- Malignant disease other than breast cancer, active or being disease-free for less than 5 years (except carcinoma in situ of the cervix, DCIS, and non-melanomatous skin cancer adequately treated).\n- Uncontrolled significant active infections including HBV, HCV, and/or HIV. Patients with a positive hepatitis B surface antigen result or a positive hepatitis C antibody test result at screening or within 3 months before first dose of study treatment are excluded, except for the following:  Participants with positive anti-HBs antibody titer and confirmatory negative hepatitis B DNA polymerase chain reaction.  Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if they have both completed curative therapy and have a hepatitis C viral load < quantifiable limit.\n- Any severe, acute, uncontrolled, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational or non-investigational products administration, or may interfere with the interpretation of study results, and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. Moreover, patients who, by virtue of an order issued by judicial or administrative authorities, are committed to an institution or those who cannot take part in clinical trials are excluded from this study.\n- History of significant neurological or psychiatric disorders including psychotic disorders, dementia, or seizures that would prohibit the understanding and giving of informed consent.\n- Unable or unwilling to avoid medications, supplements (e.g., St. John’s wort), or foods (e.g., grapefruit, pomegranate, pomelos, star fruit, Seville oranges and their juices) that are moderate/strong inhibitors or inducers of CYP3A4 activity. Participation will be allowed if the medication, supplements, or foods are discontinued for at least 14 days prior to study entry and for the duration of the study.\n- Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.\n- Receipt of live attenuated vaccination within 30 days prior to study entry. COVID-19 vaccines that do not contain live viruses are allowed (at least one week prior to study entry).\n- 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.\n- 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.\n- Inadequate organ function prior to enrolment including: o Hemoglobin < 9 g/dL (< 5.6 mmol/L) o Absolute neutrophil count (ANC) < 1500/mm³ (< 1.5 x 10^9/L) o Platelets < 100,000/mm³ (< 100 x 10^9/L) o Alanine aminotransferase (ALT/SGPT) and/or aspartate aminotransferase (AST/SGOT) > 3 x upper normal limits (ULN). If the patient has liver metastases, ALT and AST should not be ≥ 5 x ULN. o Alkaline phosphatase (ALP) > 2.5 x ULN o Total serum bilirubin > 1.5 x ULN (exception: patients with Gilbert’s syndrome permitted up to ≤ 3 x ULN) o Serum creatinine > 1.5 x ULN or estimated creatinine clearance < 50 mL/min as calculated using the standard method for the institution.\n- Existing contraindication against the use of the elacestrant or olaparib.\n- Prior treatment with PARP inhibitors.\n- Female patients: pregnancy or lactation at the time of randomization or intention to become pregnant during the study and for a predefined period after the end of treatment (as described in protocol). Male patients: intention to get a child during the study and for a predefined period after the end of treatment (as described in protocol). According to the treatment received during the study, required contraception timelines for female and male patient after the end of therapy differ (refer to the study protocol).\n- Any of the following within 6 months prior to enrolment: myocardial infarction, severe/unstable angina, ongoing grade ≥ 2 cardiac dysrhythmias, prolonged QT corrected by Fridericia’s formula (QTcF) grade ≥ 2, uncontrolled atrial fibrillation of any grade, coronary/peripheral artery bypass graft, heart failure of New York Heart Association (NYHA) Class II or greater, or cerebrovascular accident including transient ischemic attack.\n- Uncontrolled hypertension at the time of screening (systolic BP > 140 mmHg or diastolic BP > 90 mmHg that has not been adequately treated or controlled)."}

Primary endpoints

• {"endpoint_text":"- PFS is defined as the time from randomization to first progression as assessed by the investigator, or death, whichever occurs first. Patients lost to follow up or progression-free at the end of the study will be censored at the date of last contact.","definition_or_measurement_approach":"PFS defined as time from randomization to first progression per investigator assessment, or death; censoring at date of last contact for lost-to-follow-up or progression-free at study end."}

Secondary endpoints

• {"endpoint_text":"- TTF is defined as time from randomization to discontinuation of treatment due to disease progression, treatment toxicity, patient´s preference, or death. Patients lost to follow up or still under treatment at the end of the study will be censored at the date of last contact.","definition_or_measurement_approach":"TTF = time from randomization to treatment discontinuation for progression, toxicity, patient preference, or death; censor at date of last contact if lost/still on treatment."}
• {"endpoint_text":"- OS is defined as the time from randomization to death due to any reason. Patients lost to follow up or alive at the end of the study will be censored at the date of last contact.","definition_or_measurement_approach":"OS = time from randomization to death from any cause; censor at date of last contact if alive/lost."}
• {"endpoint_text":"- Patient reported BC-specific QoL as measured by FACT–ES.","definition_or_measurement_approach":"Patient-reported breast cancer-specific quality of life measured using the FACT–ES instrument."}
• {"endpoint_text":"- ORR is defined as the percentage of patients who have achieved either a confirmed complete response or partial response.","definition_or_measurement_approach":"ORR = proportion of patients with confirmed complete or partial response (per investigator assessment as specified in protocol)."}
• {"endpoint_text":"- CBR is defined as the percentage of patients who have achieved either a confirmed complete response or partial response, or stable disease for at least 24 weeks from randomization.","definition_or_measurement_approach":"CBR = proportion with confirmed CR or PR, or stable disease lasting ≥24 weeks from randomization."}
• {"endpoint_text":"- Frequency and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.","definition_or_measurement_approach":"Safety assessed by frequency and severity of adverse events graded per NCI-CTCAE v5.0."}
• {"endpoint_text":"- Dose reductions, dose delays, treatment interruptions, and treatment discontinuation rates.","definition_or_measurement_approach":"Descriptive reporting of dose modifications (reductions, delays), interruptions, and discontinuation rates."}

Germany

Earliest CTIS Part Ii Submission Date

28-02-2024

Latest Decision Or Authorization Date

17-07-2025

Processing Time Days

505

Number Of Sites

36

Number Of Participants

176

Primary sponsor

Full Name

GBG Forschungs GmbH

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Philipps-Universitaet Marburg","duties_or_roles":"central pathology testing","organisation_type":"Educational Institution"}
• {"country":"Germany","full_name":"Dr. Nibler & Partner mbB Aerzte","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Berlin-Chemie AG","duties_or_roles":"PK-analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"BioKryo GmbH","duties_or_roles":"storage of frozen blood samples","organisation_type":"Pharmaceutical company"}