A Study of Samuraciclib and Elacestrant in Participants With Metastatic or Locally Advanced HR+/HER2-negative Breast Cancer

Breast Cancer Clinical Trial

— SUMIT-ELA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05963997
• Other study ID #: CT7001_003
• Secondary ID: 2023-503846-30-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 9, 2023
• Est. completion date: June 16, 2025

Study information

• Verified date: May 2024
• Source: Carrick Therapeutics Limited
• Contact: Clinical Operations
• Phone: +353 1 5996873
• Email: hello[@]carricktherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: June 16, 2025
• Est. primary completion date: December 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Locally Advanced Breast Cancer
• Metastatic Breast Cancer

Intervention

Drug:
• Samuraciclib
Samuraciclib capsules by mouth once a day
• Elacestrant Dihydrochloride
Elacestrant tablets by mouth once a day

Locations

Country	Name	City	State
France	Site 81 - Bergonie unicancer, Nouvelle-Aquitaine, L'Institut Bergonie	Bordeaux
France	Site 80 - Centre Jean Bernard, Clinique Victor Hugo	Le Mans
France	Site 84 - UNICANCER, Centre Leon-Berard (CLB)	Lyon
France	Site 83 - Institut Paoli Calmettes (IPC)	Marseille
France	Site 85 - Institut Curie	Paris
France	Site 82 - Institut de Cancerologie de Ouest (ICO)	Saint-Herblain
Spain	Site 65 - Complexo Hospitalario Universitario A Coruña	A Coruña
Spain	Site 64 - Hospital Clinic de Barcelona (Hospital Clinic i Provincial)	Barcelona
Spain	Site 68 -Hospital Universitario Vall d'Hebron	Barcelona
Spain	Site 61 - Institut Catala d'Oncologia (ICO), Hospital Duran i Reynals Location	L'Hospitalet De Llobregat
Spain	Site 62 - Universidad de Navarra, Clinica Universidad de Navarra (CUN)	Madrid
Spain	Site 63 - South Texas Accelerated Research Therapeutics, CIOCC, Hospital Madrid Norte-Sanchinarro	Madrid
Spain	Site 66 - Hospital Clinico San Carlos	Madrid
Spain	Site 69 - Universidad de Navarra - Clinica Universidad de Navarra (CUN)	Pamplona
Spain	Site 60 - NEXT Oncology EU Hospital Universitario Quiron Salud Madrid	Pozuelo de Alarcon
Spain	Site 67 - Universidad de Sevilla, Hospital Universitario Virgen Macarena	Sevilla
United Kingdom	Site 12 - Belfast City Hospital	Belfast
United Kingdom	Site 4 - The Christie NHS Foundation Trust	Manchester
United Kingdom	Site 13 - Nottingham City Hospital	Nottingham
United Kingdom	Site 2 - Oxford University Hospitals NHS Trust - Churchill Hospital	Oxford
United States	Site 40 - Massachusetts General Hospital	Boston	Massachusetts
United States	Site 42 - Dana-Farber Cancer Institute, EDDC	Boston	Massachusetts
United States	Site 38 - Northwestern University, Feinberg School of Medicine, Northwestern University	Chicago	Illinois
United States	Site 35 - Cleveland Clinic, Taussig Cancer Institute	Cleveland	Ohio
United States	Site 43 - Mid Florida Hematology and Oncology Center	Orange City	Florida
United States	Site 41 - The START Center for Cancer Care, South Texas Oncology and Hematology	San Antonio	Texas
United States	Site 32 - Swedish Medical Center, Swedish Cancer Institute (SCI),Cherry Hill Campus	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Carrick Therapeutics Limited	Berlin-Chemie AG Menarini Group

Countries where clinical trial is conducted

United States,  France,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b (Dose-finding)	Identification of Samuraciclib + Elacestrant combination, Phase 2, expansion dose level.; Incidence and severity of adverse events as graded by the National Cancer Institute Common Terminology Criteria for Adverse events (NCI-CTCAE) v5.0. Safety will be assessed by monitoring treatment - emerged severe and dose limiting adverse events and clinically relevant changes in vital signs and clinical laboratory results	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
Primary	Phase 2 (Expansion)	Progression Free Survival (PFS) is defined as the time from the date of first dose of IMP (Cycle 1 Day 1) to the date of the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurs first.	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	Treatment-Emergent Adverse Events and Laboratory Abnormalities (Safety and Tolerability)	Type, incidence, severity (as graded by CTCAE v5.0), seriousness and relationship to study medications of AEs and any laboratory abnormalities. Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.	From the date of first dose of any study intervention through 28 days after the last dose of any study intervention
Secondary	Clinical Benefit Response (CBR)	CBR is defined as the overall complete response (CR), partial response (PR), or stable disease (SD) = 24 weeks according to RECIST version 1.1 recorded from enrolment until disease progression, or death due to any cause.	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)
Secondary	Overall response rate (ORR)	ORR is defined as the proportion of participants with a reduction in tumor burden with CR or PR according to RECIST version 1.1.; ORR will be estimated for participants who received at least 1 dose of IMP, had measurable disease at baseline and had a postbaseline tumor assessment.	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)
Secondary	Duration of Response (DOR)	DOR is defined as the time from the date of first documentation of objective tumor response (CR or PR) to the earliest documented disease progression per RECIST version 1.1	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)
Secondary	Best percent change in tumor size.	Best percent change in tumor size is defined as the percentage change in the sum of the longest diameters of target lesions	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)
Secondary	Samuraciclib plasma exposure: Cmax	Plasma concentration for Samuraciclib	Day 1 of Cycles 1 and Cycle 2 (each cycle is 28 days)
Secondary	Elacestrant exposure: Cmax	Plasma concentrations for Elacestrant	Day 1 of Cycles 1 and Cycle 2 (each cycle is 28 days)
Secondary	Samuraciclib plasma exposure: Ctrough		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)]
Secondary	Elacestrant exposure: Ctrough		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)
Secondary	Genotyping for ESR1 and TP53 mutations	Genotyping for ESR1 and TP53 mutations to evaluate correlations between ESR1 and TP53 mutations and efficacy/safety findings	Screening