A PoC Study to Evaluate Treatments' Efficacy by Monitoring MRD Using ctDNA in HR-positive/HER2-negative EBC Population

Sponsor
MedSIR
Study ID
NCT05708235
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Giredestrant — DRUG
    Giredestrant is a highly potent, non-steroidal, oral selective ER antagonist and degrader (SERD)
  • Abemaciclib — DRUG
    Abemaciclib is an orally administered CDK4/6 inhibitor
  • Inavolisib — DRUG
    Inavolisib is a potent, selective inhibitor of the Class I phosphatidylinositol 3-kinase α (PI3K-alpha isoform (p110-alpha)

Study Details

This trial is a multicenter, open-label, non-comparative, phase II, biomarker-driven adjuvant treatment study involving the periodic collection and analysis of blood samples from patients with HR-positive/HER2-negative early-stage BC at higher risk of relapse, who have undergone surgery within the previous five years, with no evidence of locoregional, contralateral, or distant disease. The study design is composed by an initial pre-screening phase, a molecular follow-up phase (ctDNA surveillance phase), and an interventional therapeutic phase (treatment phase). After informed consent is obtained, a total of 976 eligible patients will enter a ctDNA surveillance in which primary tumor tissue and matched normal blood will be collected from each patient to obtain a patient-specific somatic mutations panel (tumor signature). At the event of ctDNA positivity, patients will be screened to enter the treatment phase of the study. Upon confirmed eligibility, a total of 40 patients will be allocated in one of the following trial's arms adopting a sequential recruitment strategy: Arm A: Control Arm (N=10) Arm B: Experimental Arm with giredestrant (N=10) Arm C: Experimental Arm with giredestrant + abemaciclib (N=10) Arm D: Experimental Arm with giredestrant + inavolisib (N=10) If the strategy of ctDNA monitoring enables physicians to identify patients at high risk of relapse and assess whether treatment at molecular relapse can improve outcome, new cohorts may be added to the study.

Key Dates

Start date
Apr 1, 2024
Status verified
Mar 2026
Primary completion
Jun 30, 2028
Completion
Jun 30, 2028

Study Design

Enrollment
976 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • No Intervention: Arm A: Control Arm
    Patients will continue receiving the same standard ET that was prescribed during the surveillance phase for a period of 90 days. This will be done in accordance with standard clinical practice and until the analysis of the primary endpoint.No changes to the prescribed ET are permitted during the 90-day period.
  • Experimental: Arm B: Experimental Arm with giredestrant
    Giredestrant: 30 mg will be taken orally (PO) once a day (QD) on Days 1 to 28 of each 28-day cycle up to five years or until disease recurrence, unacceptable toxicity, or treatment/study discontinuation (whichever occurs first).
  • Experimental: Arm C: Experimental Arm with giredestrant + abemaciclib
    * Giredestrant: 30 mg will be taken PO QD on Days 1to 28 of each 28-day cycle up to five years or until disease recurrence, unacceptable toxicity, or treatment/study discontinuation (whichever occurs first). * Abemaciclib 150mg will be taken PO twice daily (BID) (two intakes for a total daily dose of 300 mg) during each 28-day cycle up to two years or until disease recurrence, unacceptable toxicity, or treatment/study discontinuation (whichever occurs first).
  • Experimental: Arm D: Experimental Arm with giredestrant + inavolisib
    * Giredestrant: 30 mg will be administered PO QD on Days 1-28 of each 28-day cycle up to five years or until disease recurrence, unacceptable toxicity, or treatment/study discontinuation (whichever occurs first). * Inavolisib: 9 mg will be administered PO QD on Days 1-28 of each 28-day cycle up to two years or until disease recurrence, unacceptable toxicity, or treatment/study discontinuation (whichever occurs first).

Primary Outcome Measure

Evaluation of decrease or clearance in baseline ctDNA at three months after initiation of study treatment [ Time Frame: Treatment phase (three months after treatment initiation) ]

Central Contacts

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