Trial Title:
Evaluating the Addition of Elacestrant (oral SERD) to Olaparib (PARP-inhibitor) in Patients with Advanced/metastatic HR+/HER2- Breast Cancer
NCT ID:
NCT06201234
Condition:
Hormone Receptor Positive HER-2 Negative Breast Cancer
Advanced or Metastatic Breast Cancer
BRCA1 Mutation
BRCA2 Mutation
Conditions: Official terms:
Breast Neoplasms
Olaparib
Conditions: Keywords:
Elacestrant
Olaparib
Breast cancer
Metastases
Palliative therapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Olaparib + Elacestrant
Description:
Olaparib 600 mg orally daily and elacestrant 400 mg orally daily
Arm group label:
Arm A: Olaparib + elacestrant*
Intervention type:
Drug
Intervention name:
Olaparib
Description:
Olaparib 600 mg orally daily
Arm group label:
Arm B: Olaparib
Summary:
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.
Detailed description:
Patients with HR-positive, HER2-negative advanced or metastatic breast cancer and
gBRCA1/2 mutations have a low progression-free survival (PFS) and represent a patient
population with a high unmet need, hence further treatment options should be explored to
improve patient outcomes.
Elacestrant is a novel, nonsteroidal, orally bioavailable estrogen receptor antagonist
(SERD) that has shown efficacy in heavily pretreated patients with HR-positive,
HER2-negative breast cancer, and in those with ESR1 mutations known to confer endocrine
resistance, and has thus gained approval in 2023 by the Food and Drug Administration
(FDA) and the European Medicines Agency (EMA) for postmenopausal women or adult men with
ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with
disease progression following at least one line of ET.
Olaparib is approved by the EMA for deleterious or suspected deleterious gBRCA-mutated,
HER2-negative metastatic BC, based on positive outcomes in the phase III OlympiAD trial
which showed improved median PFS, response rates, and less toxicity with olaparib
compared to SOC.
The purpose of the proposed study is to investigate if the addition of elacestrant to
standard olaparib therapy could potentially lead to an improvement in PFS compared to
olaparib alone in patients with HR-positive, HER2-negative locally advanced or metastatic
breast cancer with gBRCA1/2 mutations.
ELEMENT is a 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Patients will be eligible for study participation only if they comply with the following
criteria:
1. 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.
2. Female or male patients.
3. Age at study entry of at least 18 years.
4. 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).
5. Patients with deleterious or suspected deleterious gBRCA1/2 detected upon local
testing.
6. Willingness and ability to provide archived formalin fixed paraffin embedded tissue
(FFPE) block or a partial block from archived tumor or metastasis.
7. Indication for standard-of-care PARP inhibitor therapy and planned treatment with
olaparib.
8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
9. 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).
10. Life-expectancy > 6 months.
11. 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.
Exclusion Criteria:
Patients will be ineligible for study participation if they fulfill any of the following
criteria:
1. Known hypersensitivity reaction to one of the compounds, excipients, or substances
used in this protocol.
2. 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.
3. 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.
4. Inadequate organ function prior to enrolment including:
- Hemoglobin < 9 g/dL (< 5.6 mmol/L)
- Absolute neutrophil count (ANC) < 1500/mm³ (< 1.5 x 109/L)
- Platelets < 100,000/mm³ (< 100 x 109/L)
- 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.
- Alkaline phosphatase (ALP) > 2.5 x ULN
- Total serum bilirubin > 1.5 x ULN (exception: patients with Gilbert's syndrome
permitted up to ≤ 3 x ULN)
- Serum creatinine > 1.5 x ULN or estimated creatinine clearance < 50 mL/min as
calculated using the standard method for the institution.
5. Existing contraindication against the use of the elacestrant or olaparib.
6. Prior treatment with PARP inhibitors.
7. 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).
8. 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.
9. Uncontrolled hypertension at the time of screening (systolic BP > 140 mmHg or
diastolic BP > 90 mmHg that has not been adequately treated or controlled).
10. 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.
11. 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.
12. History of endometrial intraepithelial neoplasia in patients who have not undergone
a hysterectomy.
13. 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).
14. 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.
15. 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.
16. History of significant neurological or psychiatric disorders including psychotic
disorders, dementia, or seizures that would prohibit the understanding and giving of
informed consent.
17. 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.
18. Concurrent treatment with other experimental drugs. Participation in another
clinical trial with any investigational not marketed drug within 30 days prior to
study entry.
19. 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).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
DIAKOVERE Henriettenstift Gynäkologie
Address:
City:
Hannover
Zip:
30559
Country:
Germany
Status:
Recruiting
Start date:
November 2024
Completion date:
December 31, 2028
Lead sponsor:
Agency:
German Breast Group
Agency class:
Other
Collaborator:
Agency:
Stemline Therapeutics, Inc.
Agency class:
Other
Source:
German Breast Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06201234
http://gbg.de
