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JOURNAL ONKOLOGIE – STUDIE
ELECTRA

Study of Abemaciclib and Elacestrant in Patients With Brain Metastasis Due to HR+/HER2- Breast Cancer

Rekrutierend

NCT-Nummer:
NCT05386108

Studienbeginn:
August 2022

Letztes Update:
22.04.2024

Wirkstoff:
Elacestrant, Abemaciclib

Indikation (Clinical Trials):
Neoplasms, Brain Neoplasms, Breast Neoplasms, Neoplasms by Site, Nervous System Neoplasms, Central Nervous System Neoplasms, Nervous System Diseases, Brain Diseases, Central Nervous System Diseases, Breast Diseases

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Stemline Therapeutics, Inc.

Collaborator:
-

Kontakt

Studienlocations
(3 von 41)

The Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool
United KingdomRekrutierend» Google-Maps
University College London Hospitals NHS Foundation Trust - University College Hospital (UCH) - Macmillan Cancer Centre
London
United KingdomRekrutierend» Google-Maps
Ansprechpartner:
Elisavet Papadimitraki» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Brief Summary:

This is a multi-site, global, open-label study that includes a phase 1b evaluation of

elacestrant in combination with abemaciclib in women and men with with or without brain

metastases from ER-positive, HER-2 negative breast cancer. Phase 1b is designed to select the

recommended phase 2 dose and will be followed by a phase 2 evaluation of elacestrant in

combination with abemaciclib in patients with active brain metastases from ER-positive, HER-2

negative breast cancer.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Patient has the signed informed consent form before any study-related activities

according to local guidelines.

2. Women or men aged ≥18 years, at the time of informed consent signature.

- Female patients may be either postmenopausal or premenopausal or perimenopausal.

Postmenopausal status is defined by:

1. Age ≥60 years

2. Age <60 years and amenorrhea for 12 or more months (in the absence of

chemotherapy, tamoxifen, toremifene, or ovarian suppression) or a follicle

stimulating hormone (FSH) value >40 mIU/mL and an estradiol value <40 pg/mL (140

pmol/L) or in postmenopausal ranges per local reference ranges

3. Documentation of prior bilateral oophorectomy, at least 1 month before first dose

of trial therapy).

3. Patient must have ER-positive, HER-2 negative tumor status as confirmed by local

laboratory testing either from a fresh biopsy or from an archival tissue obtained no

more than 2 years prior to signing of the informed consent form.

- ER and HER-2 testing must be performed in the following manner:

- Documentation of ER positive tumor with ≥ 1% staining by immunohistochemistry

(IHC) as defined in the 2010 or 2020 American Society for Clinical Oncology

(ASCO) recommendations for ER testing, with or without progesterone receptor

(PGR) positivity

- HER-2 negative tumor with an IHC result of 0 or 1+ for cellular membrane protein

expression or an in situ hybridization negative result as defined in the 2013 or

2018 ASCO recommendations for HER-2 testing

4. Patients receiving concomitant corticosteroids must be on a stable or decreasing dose

for at least 7 days prior to baseline and not receiving doses higher than 4 mg of

dexamethasone per day or equivalent.

5. Any neurological symptoms of brain metastases must be stable for at least 2 weeks

before starting trial therapy.

6. Patient has received prior therapy in the metastatic setting including:

- At least one endocrine therapy

- Up to two chemotherapy regimens

- Up to two prior CDK 4/6 inhibitors, not including abemaciclib

- If recurrence was observed while on adjuvant therapy or within 12 months of end

of adjuvant therapy, this therapy will be counted as part of required prior

therapy for eligibility.

- Toxicity from prior therapy must be resolved to National Cancer Institute (NCI)

CTCAE version 5.0 Grade ≤1, with the exception of alopecia and peripheral sensory

neuropathy (Grade ≤2).

7. Patient has documented intra- and/or extra-cranial radiological progression or

recurrence while on or after the most recent therapy.

8. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

9. Patient has adequate bone marrow and organ function, as defined by the following

laboratory values:

1. Absolute neutrophil count (ANC) ≥1.5 × 109/L

2. Platelets ≥100 × 109/L

3. Hemoglobin ≥9.0 g/dL

4. Potassium, sodium, calcium (corrected for serum albumin) and magnesium CTCAE

Grade ≤1 (if screening assessments are abnormal, these assessments may be

repeated up to 2 times; subjects may receive appropriate supplementation or

treatment prior to reassessment)

5. Creatinine clearance (per Cockcroft-Gault formula) ≥50 mL/min

6. Serum albumin ≥3.0 g/dL (≥30 g/L)

7. In absence of liver metastases, alanine aminotransferase (ALT) and aspartate

aminotransferase (AST) ≤3.0 × ULN. If the patient has liver metastases, ALT and

AST ≤5 × ULN

8. Total serum bilirubin <1.5 × ULN except for patients with Gilbert's syndrome who

may be included if the total serum bilirubin is ≤3.0 × ULN or direct bilirubin ≤

1.5 × ULN

10. The patient is able and willing to adhere to the study visit schedule and other

protocol requirements.

11. For Phase 1b, the presence of brain metastases is allowed but not required for

eligibility. In Phase 2, patients must have at least one active and measurable brain

metastasis per RECIST version 1.1

- Any of the following qualifies brain metastases as active:

1. Newly diagnosed brain metastasis in patients who never received prior

CNS-directed therapy.

2. Newly diagnosed brain metastasis outside any area that was previously

subjected to CNS-directed therapy

3. Brain metastases that are progressing in an area that has previously been

subjected to CNS-directed therapy

- For lesions, including brain metastases, to qualify as measurable, and possibly

be selected as target lesions, per RECIST version 1.1 (Appendix C), the longest

diameter must be ≥10 mm by CT or magnetic resonance imaging (MRI).

Exclusion Criteria:

1. Immediate CNS-specific treatment is likely to be required, per the treating

physician's assessment.

2. Patient has imminent organ failure and/or visceral crisis.

3. Patient has leptomeningeal metastases, defined as having positive CSF cytology or

unequivocal radiologic or clinical evidence of leptomeningeal involvement.

4. Breast cancer treatment-naïve patients in the metastatic setting. Patients who

experience a recurrence while on adjuvant therapy or within 12 months of end of

adjuvant therapy are allowed.

5. Prior therapy with abemaciclib in the metastatic setting. Note: Use of abemaciclib in

the adjuvant setting is allowed if the last treatment administration was more than 12

months prior to first recurrence.

6. Prior therapy with elacestrant or other investigational SERDs, or alike agents such as

SERMs, SERCANs, CERANs, and PROTACs in the metastatic setting.

7. Patient has a concurrent malignancy or malignancy within 3 years of enrollment, with

the exception of adequately treated basal or squamous cell skin cancer, superficial

bladder cancer, carcinoma in situ of the cervix, or second primary breast cancer.

8. Currently participating in another breast cancer intervention clinical study. Patients

who are being followed for overall survival for another clinical trial with no therapy

and study intervention are allowed after the washout period for any prior therapy.

9. Prior anti-cancer or investigational drug treatment within the following windows:

- Fulvestrant treatment (last injection) <42 days before first dose of study drug

- Any other endocrine therapy <14 days or <5 half-lives, whichever is shorter,

before first dose of study drug

- Chemotherapy or other anti-cancer therapy <21 days before first dose of study

drug

- Any investigational anti-cancer drug therapy within <28 days or <5 half lives,

whichever is shorter

- Bisphosphonates or RANKL inhibitors initiated, or dose changed <1 month prior to

first dose of study drug.

10. Radiation therapy (other than CNS directed) within 14 days before the first dose of

study drug.

11. Uncontrolled significant active infections

- Patients with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection

must have undetectable viral load during screening

- Patients known to be HIV+ are allowed as long as they have undetectable viral

load at baseline.

12. Major surgery within 4 weeks of starting trial therapy.

13. Inability to take oral medication, or history of malabsorption syndrome or any other

uncontrolled gastrointestinal condition.

14. Females of childbearing potential who do not agree to use a highly effective

non-hormonal method of contraception throughout within 28 days of the first dose of

study treatment until 28 days of the last dose of study treatment. Highly effective

non-hormonal method of contraception includes any of the following:

1. Intrauterine device (non-hormonal)

2. Total abstinence

3. Bilateral tubal occlusion/ligation

4. Have a vasectomized partner with confirmed azoospermia.

15. Men who do not agree abstain from donating sperm or to use a highly effective barrier

contraception (use condoms) during the treatment period and for 120 days thereafter.

For subjects (who have not undergone vasectomy) with female partners of childbearing

potential, the subject and his partner must, in addition to condoms, use highly

effective methods of contraception.

16. Females who are breastfeeding or pregnant.

17. Known intolerance to either study drug or any of the excipients.

18. Patients currently receiving or received any of the following medications prior to

first dose of trial therapy:

1. Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4

within 21 days prior to initiating trial therapy

2. Herbal preparations/medications These include, but are not limited to, St. John's

wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA),

yohimbe, saw palmetto, and ginseng within 21 days prior to initiating trial

therapy

3. Vaccination, including but not limited to vaccination against COVID-19, during

the 7 days prior to randomization.

19. Any severe medical or psychiatric condition that in the opinion of the investigator(s)

would preclude the patient's participation in a clinical study.

Studien-Rationale

Primary outcome:

1. RP2D (Time Frame - 1 year):
Based on the observed number of dose-limiting toxicities (DLTs) during the first cycle. Dose-limiting toxicity is based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Dose-limiting toxicities will be evaluated during the first cycle (28 days) of treatment in up to 3 cohorts during Phase 1b. A DLT will be defined as any of the toxicities listed in the protocol that are not clearly due to breast cancer or extraneous causes.

2. Objective Response Rate (Time Frame - 3 years):
Defined as the proportion of patients with a best overall response of either a complete response or partial response per blinded independent central review, per RECIST version 1.1.

Secondary outcome:

1. Intracranial Response Rate per Response Evaluation Criteria in Solid Tumors (RECIST) (Time Frame - 3 years):
Defined as the proportion of patients achieving a best overall response of confirmed partial response + complete response, based on intracranial lesions per RECIST version 1.1 and blinded independent central review.

2. Intracranial Response Rate per Response Assessment in Neuro-Oncology (RANO) (Time Frame - 3 years):
Defined as the proportion of patients achieving a best overall response of confirmed partial response plus complete response, based on intracranial lesions (per RANO criteria) and per blinded independent central review.

3. Duration of Tumor Response (Time Frame - 3 years):
Defined as the duration of time from the date when criteria are met for either a complete response or partial response, per RECIST v1.1, until the first date that progressive disease is objectively documented, per blinded independent central review.

4. Clinical Benefit Rate (Time Frame - 3 years):
Defined as the proportion of patients who have the best overall response a complete response, a partial response, or stable disease.

5. Duration of Progression-Free Survival (Time Frame - 3 years):
Defined as the time elapsing between the start of treatment and the date of the earliest evidence of objective disease progression or death of any cause before documented disease-progression assessed through study completion.

Studien-Arme

  • Experimental: Phase 1b Cohort 1
    Elacestrant 300 mg once daily (QD) + abemaciclib 100 mg twice daily (BID)
  • Experimental: Phase 1b Cohort 2
    Elacestrant 400 mg QD + abemaciclib 100 mg BID
  • Experimental: Phase 1b Cohort 3
    Elacestrant 400 mg QD + abemaciclib 150 mg BID
  • Experimental: Phase 2
    Elacestrant in combination with abemaciclib at the recommended phase 2 dose (RP2D) determined in phase 1b

Geprüfte Regime

  • Elacestrant (ELA-0121):
    300 mg, 400 mg
  • Abemaciclib (Verzenio):
    100 mg, 150 mg

Quelle: ClinicalTrials.gov


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