Clinical trial NCT05963997: A Study of Samuraciclib and Elacestrant in Participants With Metastatic or Locally Advanced HR+/HER2-negative Breast Cancer
Official title: A Phase 1b/2 Open-label Study of Samuraciclib in Combination With Elacestrant in Participants With Metastatic or Locally Advanced Hormone Receptor-positive and Human Epidermal Growth Factor Receptor 2-negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Breast Cancer
Locally Advanced Breast Cancer
Breast Cancer
Keywords: Metastatic Breast Cancer
Advanced Breast Cancer
Breast Cancer
HR Positive
HER2-Negative
Lead sponsor: Carrick Therapeutics Limited
Sponsor class: INDUSTRY
Collaborators: name: Berlin-Chemie AG Menarini Group
First posted: 2023-07-27
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an international, multisite, open-label, Phase 1b/2 study, to confirm safety and efficacy of samuraciclib in combination with elacestrant in adult participants with metastatic or locally advanced Hormone Receptor (HR) positive and Human Epidermal Growth Factor Receptor (HER)2-negative breast cancer.

Detailed description: This is a multiple cohort study, an initial dose escalation phase is designed to confirm the safe dose of samuraciclib in combination with elacestrant. A Safety Review Committee (SRC) will monitor the safety, tolerability, and PK data during this phase. Once ascertained, an expansion cohort will be opened to explore the efficacy of samuraciclib in combination with elacestrant.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed diagnosis of ER-positive, HER2-negative locally advanced or metastatic breast cancer.
* Documented objective disease progression while on or within 6 months after the end of the most recent therapy.
* Received prior AI in combination with a CDK4/6i as the last therapy
* Known TP53 and ESR1 mutation status.
* Participants must have measurable disease or bone only disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
* Pre/peri-menopausal participants must have commenced treatment with a luteinizing hormone-releasing hormone (LHRH) agonist at least 4 weeks prior to first dose of study intervention.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1 with no deterioration over the past 2 weeks.
* Expected life expectancy of \>12 weeks in the judgement of the treating investigator.

Exclusion Criteria:

* Inflammatory breast cancer.
* Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
* More than 1 line of endocrine treatment for locally advanced or metastatic disease treatment.
* Inadequate hepatic, renal, and bone marrow function.
* Clinically significant cardiovascular disease.
* Any current or prior central nervous system metastases, carcinomatous meningitis, or leptomeningeal disease.
* Pregnant or breastfeeding women.

Primary outcomes:
measure: Phase 1b (Dose-finding)
timeFrame: From the date of first dose of any study intervention (Day 1 Cycle 1) and through 28 days after the last dose of any study intervention
measure: Phase 2 (Expansion)
timeFrame: From the date of first dose of any study intervention (Cycle 1 Day 1) until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48)
Secondary outcomes:
measure: Treatment-Emergent Adverse Events and Laboratory Abnormalities (Safety and Tolerability)
timeFrame: From the date of first dose of any study intervention through 28 days after the last dose of any study intervention
measure: Clinical Benefit Response (CBR)
timeFrame: From the date of first dose of any study intervention (Cycle 1 Day 1) to ≥ 24 weeks or until disease progression or death to any cause (assessed up to week 24)
measure: Overall response rate (ORR)
timeFrame: the date of first dose of study intervention (Cycle 1 Day 1) until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48)
measure: Duration of Response (DOR)
timeFrame: From the date of first dose of study intervention (Cycle 1 Day 1) until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48)
measure: Best percent change in tumor size.
timeFrame: From the date of first dose of study intervention (Cycle 1 Day 1) until the first documentation of disease progression, death, withdrawal of consent, or start of new anticancer therapy (assessed up to week 48)
measure: Samuraciclib plasma exposure: Cmax
timeFrame: Day 1 of Cycles 1 and Cycle 2 (each cycle is 28 days)
measure: Elacestrant exposure: Cmax
timeFrame: Day 1 of Cycles 1 and Cycle 2 (each cycle is 28 days)
measure: Samuraciclib plasma exposure: Ctrough
timeFrame: Cycle 1 Day 2 and 15; Day 2 of Cycle 2; Day 1 of Cycles 3-6 and end of treatment within 28 days of last dose of IMP and prior to the initiation of a new anticancer therapy (each cycle is 28 days)]
measure: Elacestrant exposure: Ctrough
timeFrame: Cycle 1 Day 2 and Day 15; Cycle 2 Day 2 of Cycle 2 and Day 1 of Cycles 3-6 and at end of treatment within 28 days of the last dose of IMP and prior to the initiation of a new anticancer therapy (each cycle is 28 days)
measure: Genotyping for ESR1 and TP53 mutations
timeFrame: Screening
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Site 38 - Northwestern University, Feinberg School of Medicine, Northwestern University
state: Illinois
city: Boston
country: United States
facility: Site 42 - Dana-Farber Cancer Institute, EDDC
state: Massachusetts
city: Cleveland
country: United States
facility: Site 35 - Cleveland Clinic, Taussig Cancer Institute
state: Ohio
city: San Antonio
country: United States
facility: Site 41 - The START Center for Cancer Care, South Texas Oncology and Hematology
state: Texas
city: Seattle
country: United States
facility: Site 32 - Swedish Medical Center, Swedish Cancer Institute (SCI),Cherry Hill Campus
state: Washington
city: Bordeaux
country: France
facility: Site 81 - Bergonie unicancer, Nouvelle-Aquitaine, L'Institut Bergonie
city: Le Mans
country: France
facility: Site 80 - Centre Jean Bernard, Clinique Victor Hugo
city: Marseille
country: France
facility: Site 83 - Institut Paoli Calmettes (IPC)
city: Paris
country: France
facility: Site 85 - Institut Curie
city: Saint-Herblain
country: France
facility: Site 82 - Institut de Cancerologie de Ouest (ICO)
city: A Coruña
country: Spain
facility: Site 65 - Complexo Hospitalario Universitario A Coruña
city: Barcelona
country: Spain
facility: Site 64 - Hospital Clinic de Barcelona (Hospital Clinic i Provincial)
city: Barcelona
country: Spain
facility: Site 68 -Hospital Universitario Vall d'Hebron
city: L'Hospitalet De Llobregat
country: Spain
facility: Site 61 - Institut Catala d'Oncologia (ICO), Hospital Duran i Reynals Location
city: Madrid
country: Spain
facility: Site 62 - Universidad de Navarra, Clinica Universidad de Navarra (CUN)
city: Madrid
country: Spain
facility: Site 63 - South Texas Accelerated Research Therapeutics, CIOCC, Hospital Madrid Norte-Sanchinarro
city: Madrid
country: Spain
facility: Site 66 - Hospital Clinico San Carlos
city: Pamplona
country: Spain
facility: Site 69 - Universidad de Navarra - Clinica Universidad de Navarra (CUN)
city: Pozuelo de Alarcon
country: Spain
facility: Site 60 - NEXT Oncology EU Hospital Universitario Quiron Salud Madrid
city: Sevilla
country: Spain
facility: Site 67 - Universidad de Sevilla, Hospital Universitario Virgen Macarena
city: Belfast
country: United Kingdom
facility: Site 12 - Belfast City Hospital
city: Manchester
country: United Kingdom
facility: Site 4 - The Christie NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Site 2 - Oxford University Hospitals NHS Trust - Churchill Hospital
Study officials:
References: