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

Primary Purpose

Metastatic Breast Cancer, Locally Advanced Breast Cancer, Breast Cancer

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Samuraciclib
Elacestrant Dihydrochloride
Sponsored by
Carrick Therapeutics Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring Metastatic Breast Cancer, Advanced Breast Cancer, Breast Cancer, HR Positive, HER2-Negative

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Site 43 - Mid Florida Hematology and Oncology CenterRecruiting
  • Site 38 - Northwestern University, Feinberg School of Medicine, Northwestern University
  • Site 40 - Massachusetts General Hospital
  • Site 42 - Dana-Farber Cancer Institute, EDDC
  • Site 35 - Cleveland Clinic, Taussig Cancer Institute
  • Site 34 -The University of Texas, MD Anderson Cancer Center, Nellie B. Connally Breast Center
  • Site 41 - The START Center for Cancer Care, South Texas Oncology and HematologyRecruiting
  • Site 32 - Swedish Medical Center, Swedish Cancer Institute (SCI),Cherry Hill Campus
  • Site 81 - Bergonie unicancer, Nouvelle-Aquitaine, L'Institut Bergonie
  • Site 80 - Centre Jean Bernard, Clinique Victor Hugo
  • Site 84 - UNICANCER, Centre Leon-Berard (CLB)
  • Site 83 - Institut Paoli Calmettes (IPC)
  • Site 85 - Institut Curie
  • Site 82 - Institut de Cancerologie de Ouest (ICO)
  • Site 65 - Complexo Hospitalario Universitario A CoruñaRecruiting
  • Site 64 - Hospital Clinic de Barcelona (Hospital Clinic i Provincial)Recruiting
  • Site 68 -Hospital Universitario Vall d'Hebron
  • Site 61 - Institut Catala d'Oncologia (ICO), Hospital Duran i Reynals Location
  • Site 62 - Universidad de Navarra, Clinica Universidad de Navarra (CUN)Recruiting
  • Site 63 - South Texas Accelerated Research Therapeutics, CIOCC, Hospital Madrid Norte-Sanchinarro
  • Site 66 - Hospital Clinico San Carlos
  • Site 69 - Universidad de Navarra - Clinica Universidad de Navarra (CUN)
  • Site 60 - NEXT Oncology EU Hospital Universitario Quiron Salud Madrid
  • Site 67 - Universidad de Sevilla, Hospital Universitario Virgen Macarena
  • Site 12 - Belfast City Hospital
  • Site 4 - The Christie NHS Foundation Trust
  • Site 13 - Nottingham City Hospital
  • Site 2 - Oxford University Hospitals NHS Trust - Churchill Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4 Expansion

Arm Description

Up to 6 evaluable participants will receive samuraciclib 240 mg in combination with elacestrant 300 mg in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onwards).

Up to 6 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 300 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).

Up to 6 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 400 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).

Up to 30 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 400 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

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.
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.
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.
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
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
Samuraciclib plasma exposure: Cmax
Plasma concentration for Samuraciclib
Elacestrant exposure: Cmax
Plasma concentrations for Elacestrant
Samuraciclib plasma exposure: Ctrough
Elacestrant exposure: Ctrough
Genotyping for ESR1 and TP53 mutations
Genotyping for ESR1 and TP53 mutations to evaluate correlations between ESR1 and TP53 mutations and efficacy/safety findings

Full Information

First Posted
June 30, 2023
Last Updated
October 20, 2023
Sponsor
Carrick Therapeutics Limited
Collaborators
Berlin-Chemie AG Menarini Group
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1. Study Identification

Unique Protocol Identification Number
NCT05963997
Brief Title
A Study of Samuraciclib and Elacestrant in Participants With Metastatic or Locally Advanced HR+/HER2-negative Breast Cancer
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 9, 2023 (Actual)
Primary Completion Date
December 23, 2024 (Anticipated)
Study Completion Date
June 16, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Carrick Therapeutics Limited
Collaborators
Berlin-Chemie AG Menarini Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer, Locally Advanced Breast Cancer, Breast Cancer
Keywords
Metastatic Breast Cancer, Advanced Breast Cancer, Breast Cancer, HR Positive, HER2-Negative

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Up to 6 evaluable participants will receive samuraciclib 240 mg in combination with elacestrant 300 mg in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onwards).
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Up to 6 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 300 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Up to 6 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 400 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).
Arm Title
Cohort 4 Expansion
Arm Type
Experimental
Arm Description
Up to 30 evaluable participants will receive samuraciclib in combination with elacestrant at the SRC recommended dose (anticipated 360mg samuraciclib, 400 mg elacestrant) in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onward).
Intervention Type
Drug
Intervention Name(s)
Samuraciclib
Intervention Description
Samuraciclib capsules by mouth once a day
Intervention Type
Drug
Intervention Name(s)
Elacestrant Dihydrochloride
Other Intervention Name(s)
ORSERDU
Intervention Description
Elacestrant tablets by mouth once a day
Primary Outcome Measure Information:
Title
Phase 1b (Dose-finding)
Description
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
Time Frame
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
Title
Phase 2 (Expansion)
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Treatment-Emergent Adverse Events and Laboratory Abnormalities (Safety and Tolerability)
Description
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.
Time Frame
From the date of first dose of any study intervention through 28 days after the last dose of any study intervention
Title
Clinical Benefit Response (CBR)
Description
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.
Time Frame
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)
Title
Overall response rate (ORR)
Description
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.
Time Frame
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)
Title
Duration of Response (DOR)
Description
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
Time Frame
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)
Title
Best percent change in tumor size.
Description
Best percent change in tumor size is defined as the percentage change in the sum of the longest diameters of target lesions
Time Frame
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)
Title
Samuraciclib plasma exposure: Cmax
Description
Plasma concentration for Samuraciclib
Time Frame
Day 1 of Cycles 1 and Cycle 2 (each cycle is 28 days)
Title
Elacestrant exposure: Cmax
Description
Plasma concentrations for Elacestrant
Time Frame
Day 1 of Cycles 1 and Cycle 2 (each cycle is 28 days)
Title
Samuraciclib plasma exposure: Ctrough
Time Frame
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)]
Title
Elacestrant exposure: Ctrough
Time Frame
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)
Title
Genotyping for ESR1 and TP53 mutations
Description
Genotyping for ESR1 and TP53 mutations to evaluate correlations between ESR1 and TP53 mutations and efficacy/safety findings
Time Frame
Screening

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Operations
Phone
+353 1 5996873
Email
hello@carricktherapeutics.com
Facility Information:
Facility Name
Site 43 - Mid Florida Hematology and Oncology Center
City
Orange City
State/Province
Florida
ZIP/Postal Code
32763
Country
United States
Individual Site Status
Recruiting
Facility Name
Site 38 - Northwestern University, Feinberg School of Medicine, Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Site 40 - Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114-2696
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Site 42 - Dana-Farber Cancer Institute, EDDC
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Site 35 - Cleveland Clinic, Taussig Cancer Institute
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Site 34 -The University of Texas, MD Anderson Cancer Center, Nellie B. Connally Breast Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Site 41 - The START Center for Cancer Care, South Texas Oncology and Hematology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Name
Site 32 - Swedish Medical Center, Swedish Cancer Institute (SCI),Cherry Hill Campus
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Site 81 - Bergonie unicancer, Nouvelle-Aquitaine, L'Institut Bergonie
City
Bordeaux
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Site 80 - Centre Jean Bernard, Clinique Victor Hugo
City
Le Mans
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Site 84 - UNICANCER, Centre Leon-Berard (CLB)
City
Lyon
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Site 83 - Institut Paoli Calmettes (IPC)
City
Marseille
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Site 85 - Institut Curie
City
Paris
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Site 82 - Institut de Cancerologie de Ouest (ICO)
City
Saint-Herblain
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Site 65 - Complexo Hospitalario Universitario A Coruña
City
A Coruña
Country
Spain
Individual Site Status
Recruiting
Facility Name
Site 64 - Hospital Clinic de Barcelona (Hospital Clinic i Provincial)
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Name
Site 68 -Hospital Universitario Vall d'Hebron
City
Barcelona
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Site 61 - Institut Catala d'Oncologia (ICO), Hospital Duran i Reynals Location
City
L'Hospitalet De Llobregat
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Site 62 - Universidad de Navarra, Clinica Universidad de Navarra (CUN)
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Name
Site 63 - South Texas Accelerated Research Therapeutics, CIOCC, Hospital Madrid Norte-Sanchinarro
City
Madrid
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Site 66 - Hospital Clinico San Carlos
City
Madrid
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Site 69 - Universidad de Navarra - Clinica Universidad de Navarra (CUN)
City
Pamplona
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Site 60 - NEXT Oncology EU Hospital Universitario Quiron Salud Madrid
City
Pozuelo de Alarcon
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Site 67 - Universidad de Sevilla, Hospital Universitario Virgen Macarena
City
Sevilla
Country
Spain
Individual Site Status
Not yet recruiting
Facility Name
Site 12 - Belfast City Hospital
City
Belfast
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Name
Site 4 - The Christie NHS Foundation Trust
City
Manchester
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Name
Site 13 - Nottingham City Hospital
City
Nottingham
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Name
Site 2 - Oxford University Hospitals NHS Trust - Churchill Hospital
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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