PIK3CA/PTEN-altered Advanced Breast Cancer Treated With MEN1611 Monotherapy or in Combination With Eribulin
- Conditions
- Advanced Breast CancerBreast CancerMetastatic Breast Cancer
- Interventions
- Registration Number
- NCT05810870
- Lead Sponsor
- MedSIR
- Brief Summary
The multicenter, two-cohort, non-comparative, open-label, phase II clinical trial SABINA aims to analyze the safety and efficacy of MEN1611 in monotherapy and in combination with eribulin, a non-taxane chemotherapy agent, in Hormone Receptor (HR)-known/Human Epidermial Growth Factor Receptor 2 (HER2)-negative, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)/ Phosphatase and Tensin Homolog (PTEN)-altered, unresectable locally advanced or metastatic metaplastic breast carcinoma (MpBC) patients.
A run-in phase for safety and tolerability of MEN1611 in combination with standard doses of eribulin will be conducted as an initial step of the cohort A. This first step aims at evaluating the dosing schedule of MEN1611, by analyzing the toxicity profile of the combined regimen.
With the background of the first-in-human study (PA-001EU), the safe dose of MEN1611 has been established as 48 mg orally BID (two intakes of 3 capsules of 16 mg each, for a total daily dose of 96 mg MEN1611 free-base).
- Detailed Description
This is a multicenter, two-cohort, non-comparative, open-label, phase II clinical trial to assess:
* the efficacy of MEN1611 in combination with eribulin as determined by the clinical benefit rate (CBR) in unresectable locally advanced or metastatic HR-known/HER2-negative, PIK3CA/ PTEN-altered MpBC patients (Cohort A), and
* the efficacy of MEN1611 as monotherapy as determined by the objective response rate (ORR) at 6 weeks in unresectable locally advanced or metastatic HR-known/HER2-negative, PIK3CA/ PTEN-altered MpBC patients (Cohort B).
Upon meeting all selection criteria, 28 patients will be enrolled as follows:
- Cohort A: A run-in phase for safety and tolerability of MEN1611 in combination with eribulin will be conducted in this patient population (N=3). A Steering Committee decision/agreement is needed, after reviewing all toxicities, to expand this cohort with 11 additional patients (up to N=14).
Cohort B will be run only if positive finding in Cohort A, defined as ≥ 6 patients (42.9%) with achieved clinical benefit (CB) among 14 first recruited patients.
- Cohort B: Simon's two-stage minimax design. Stage I (N=7) will be initiated with MEN1611 monotherapy. This cohort will be stopped for futility if no responders (no complete response \[CR\] or partial response \[PR\]) are observed after 2 cycles among the first 7 patients included. Otherwise, Cohort B will be expanded with 7 additional patients for Stage II (up to N=14).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 14
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort A MEN1611 MEN1611 orally (PO) 48 mg twice daily (BID) (2 intakes of 3x16 mg capsules, for a total daily dose of 96 mg MEN1611 free-base) during each 21-day cycle combined with eribulin mesylate 1.4 mg/m2 (equivalent to eribulin 1.23 mg/m2 when expressed as a free base) administered intravenously (IV) over 2 to 5 minutes on days 1 and 8 of every 21-day cycle (CXD1 and CXD8). A run-in phase for safety and tolerability of MEN1611 in combination with eribulin will be conducted after the first 2 cycles on the first 3 patients. Upon Steering Committee agreement the cohort A will be expanded up to N=14 (11 additional patients). Patients will receive treatment until disease progression, unacceptable toxicity, death, discontinuation from the study treatment for any other reason, withdrawal of consent, or study termination. Cohort A Eribulin MEN1611 orally (PO) 48 mg twice daily (BID) (2 intakes of 3x16 mg capsules, for a total daily dose of 96 mg MEN1611 free-base) during each 21-day cycle combined with eribulin mesylate 1.4 mg/m2 (equivalent to eribulin 1.23 mg/m2 when expressed as a free base) administered intravenously (IV) over 2 to 5 minutes on days 1 and 8 of every 21-day cycle (CXD1 and CXD8). A run-in phase for safety and tolerability of MEN1611 in combination with eribulin will be conducted after the first 2 cycles on the first 3 patients. Upon Steering Committee agreement the cohort A will be expanded up to N=14 (11 additional patients). Patients will receive treatment until disease progression, unacceptable toxicity, death, discontinuation from the study treatment for any other reason, withdrawal of consent, or study termination.
- Primary Outcome Measures
Name Time Method To assess the efficacy of MEN1611 in combination with eribulin as determined by the clinical benefit rate (CBR). Baseline up to at least 12 weeks CBR, defined as the percentage of patients who experience a complete response (CR), partial response (PR) or stable disease (SD) for at least 12 weeks after the start of MEN1611 in combination with eribulin treatment, as determined locally by the investigator per RECIST v1.1 criteria.
- Secondary Outcome Measures
Name Time Method To determine the efficacy of MEN1611 in combination with eribulin defined as ORR of patients. Baseline up to 24 months ORR, defined as the proportion of patients with confirmed CR or PR who received MEN1611 in combination with eribulin treatment as determined locally by the Investigator as per RECIST v1.1 criteria.
To determine the efficacy of MEN1611 in combination with eribulin defined as Time To Response (TTR). Baseline up to 24 months TTR, defined as the time from the start of MEN1611 in combination with eribulin treatment to the first objective tumor response (tumor shrinkage of ≥ 30%).
To determine the efficacy of MEN1611 in combination with eribulin defined as Duration of Response (DoR) of patients. Baseline up to 24 months DoR defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first.
To determine the efficacy of MEN1611 in combination with eribulin defined as Progression-Free Survival (PFS). Baseline up to 24 months PFS defined as the time from the first dose of Study drugs until objective tumor progression or death, whichever occurs first.
To determine the efficacy of MEN1611 in combination with eribulin defined as Overall Survival (OS). Baseline up to 24 months OS defined as the time from the first dose of Study drugs until death from any cause.
To assess the safety and tolerability of MEN1611 in combination with eribulin defined as incidence and severity of adverse events. Baseline up to 24 months To evaluate the incidence of AEs of MEN1611 in combination with eribulin as assessed by the Investigator, with severity determined by NCI-CTCAE v.5.0.
Trial Locations
- Locations (13)
Hospital Universitario Clínico San Cecilio de Granada
🇪🇸Granada, Andalucia, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Andalucia, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Cantabria, Spain
Centro Oncológico de Galicia
🇪🇸A Coruña, Galicia, Spain
Hospital Universitario de Torrejón
🇪🇸Torrejón De Ardoz, Madrid, Spain
Onkologikoa
🇪🇸San Sebastián, Pais Vasco, Spain
CHUVI - Complejo Hospitalario Universitario de Vigo
🇪🇸Vigo, Pontevedra, Spain
Hospital Clínic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Institut Català d' Oncologia L'Hospitalet (ICO)
🇪🇸Barcelona, Spain
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Beata María Ana
🇪🇸Madrid, Spain
Instituto Valenciano de Oncología (IVO)
🇪🇸Valencia, Spain