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Study of Abemaciclib and Elacestrant in Patients With Brain Metastasis Due to HR+/Her2- Breast Cancer (ELECTRA)

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ClinicalTrials.gov Identifier: NCT05386108
Recruitment Status : Recruiting
First Posted : May 23, 2022
Last Update Posted : September 9, 2022
Sponsor:
Information provided by (Responsible Party):
Stemline Therapeutics, Inc.

Brief Summary:
This is a multi-site, global, open label study which 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 randomized Phase 2 evaluation of elacestrant alone or in combination with abemaciclib in women and men with brain metastases from ER positive, HER-2 negative breast cancer.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Brain Neoplasms Neoplasms by Site Neoplasms Breast Diseases Central Nervous System Neoplasms Brain Diseases Central Nervous System Diseases Drug: Abemaciclib Drug: Elacestrant Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 106 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Multicenter Phase 1b-2 Study of Elacestrant as Monotherapy and in Combination With Abemaciclib in Women and Men With Brain Metastasis From Estrogen Receptor Positive, HER-2 Negative Breast Cancer
Actual Study Start Date : August 31, 2022
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Abemaciclib

Arm Intervention/treatment
Experimental: Phase 1b Cohort 1
Elacestrant 300 mg QD + abemaciclib 100 mg BID.
Drug: Abemaciclib
400 mg
Other Name: Verzenio

Drug: Elacestrant
100 mg, 150 mg

Experimental: Phase 1b Cohort 2
400 mg QD + abemaciclib 100 mg BID.
Drug: Abemaciclib
400 mg
Other Name: Verzenio

Drug: Elacestrant
100 mg, 150 mg

Experimental: Phase 1b Cohort 3
Elacestrant 400 mg QD + abemaciclib 150 mg BID
Drug: Abemaciclib
400 mg
Other Name: Verzenio

Drug: Elacestrant
100 mg, 150 mg

Active Comparator: Phase 2 Arm A
Elacestrant monotherapy at 400 mg QD.
Drug: Elacestrant
100 mg, 150 mg

Active Comparator: Phase 2 Arm B
Elacestrant in combination with abemaciclib at the RP2D determined in Phase 1b.
Drug: Abemaciclib
400 mg
Other Name: Verzenio

Drug: Elacestrant
100 mg, 150 mg




Primary Outcome Measures :
  1. The number of patients in the Phase 1b part of the study with any adverse events (AE). [ Time Frame: 1 year ]
    To determine the safety and tolerability of the abemaciclib and elacestrant combination the number of patients with adverse events (AE) that occur on or after C1D1 of therapy, AE severities will be classified using the CTCAE v5.0.

  2. Assess the efficacy of the drug combination of abemaciclib and elacestrant in the Phase 2 part of the study [ Time Frame: 3 years ]
    Determine the objective response rate (ORR; the proportion of patients with a best overall response of either a complete response or partial response) per blinded independent central review


Secondary Outcome Measures :
  1. Intracranial Response Rate per blinded independent central review (RECIST 1.1) [ 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).

  2. Intracranial Response Rate per blinded independent central review (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).

  3. Duration of Tumor Response [ Time Frame: 3 years ]
    Measured as the time from the date of enrollment until the first date of documented disease progression or death due to any cause, whichever occurs first.

  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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 surgical sterilization (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, at least 1 month before first dose of trial therapy).
  • Premenopausal or perimenopausal women must be concurrently given a luteinizing hormone-releasing hormone (LHRH) agonist starting at least 4 weeks before the start of trial therapy and is planning to continue LHRH during the study.
  • For perimenopausal women to be considered of non-childbearing potential, FSH levels must be >40 mIU/ml.

    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. For Phase 1b, the presence of brain metastases is allowed but not required for eligibility, in this case, at least 1 measurable lesion outside the brain is required.

  • 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. 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).

    5. Patients must be off corticosteroids or receiving a stable or decreasing corticosteroid dose at the time of starting trial therapy. The dose must be ≤2.0 mg/day of dexamethasone or equivalent.

    6. Any neurological symptoms of brain metastases must be stable for at least 4 weeks before starting trial therapy.

    7. 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).

    8. Patient has documented intra- and/or extra-cranial radiological progression or recurrence while on or after the most recent therapy.

    9. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 10. Patient has adequate bone marrow and organ function, as defined by the following laboratory values (in the absence of transfusion of red blood cells or platelets or the use of growth factors within the preceding 4 weeks):

    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 11. The patient is able and willing to adhere to the study visit schedule and other protocol requirements.

      Exclusion Criteria:

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

      2. Patient has leptomeningeal metastases, defined as having positive CSF cytology or unequivocal radiologic or clinical evidence of leptomeningeal involvement.

      3. 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.

      4. Prior therapy with elacestrant or 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.

      5. 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).

      6. 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.

      7. 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 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 <3 months prior to first dose of study drug.

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

      9. 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.

        10. Major surgery within 4 weeks of starting trial therapy. 11. Inability to take oral medication, or presence of malabsorption syndrome or any other uncontrolled gastrointestinal condition.

        12. Females of childbearing potential who:

      • Within 28 days of study entry, did not use a highly effective method of contraception, which includes any of the following:
    1. Intrauterine device
    2. Double-barrier contraception
    3. Total abstinence
    4. Have a vasectomized partner with confirmed azoospermia. • Do not agree to use a highly effective method of contraception, as described above, throughout the entire study period and for 28 days after trial therapy discontinuation.

      13. Men who do not agree abstain from donating sperm or to use a highly effective method of contraception during the treatment period and for 120 days thereafter. Highly effective methods include any of the following:

    a. Double-barrier contraception b. Total abstinence c. Vasectomized with confirmed azoospermia. d. Female partner with intrauterine device. 14. Females who are breastfeeding or pregnant. 15. Known intolerance to either study drug or any of the excipients. 16. Patients currently receiving or received any of the following medications prior to first dose of trial therapy:

    a. Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within 21 days prior to initiating trial therapy b. 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 c. Vaccination, including but not limited to vaccination against COVID-19, during the 7 days prior to randomization.

    17. Any medical or other condition that in the opinion of the investigator(s) would preclude the patient's participation in a clinical study.

    18. Evidence of ongoing alcohol or drug abuse


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05386108


Contacts
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Contact: Stemline Trials 718-509-3742 trials@stemline.com
Contact: Mary Ann Samparani 646-731-2146 msamparani@stemline.com

Locations
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United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States, 44718
Contact: Nashat Gabrail    330-492-3345      
Sponsors and Collaborators
Stemline Therapeutics, Inc.
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Responsible Party: Stemline Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05386108    
Other Study ID Numbers: ELA-0121
First Posted: May 23, 2022    Key Record Dates
Last Update Posted: September 9, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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
Skin Diseases