A PoC Study to Evaluate Treatments' Efficacy by Monitoring MRD Using ctDNA in HR-positive/HER2-negative EBC Population
ConditionBreast Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMedSIR
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Signed informed consent form (ICF) prior to participation in any Studyrelated activities.
Male or female patients aged 18 years or older.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Histologically proven primary HR-positive according to the updated American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2020 guidelines and HER2-negative BC as per ASCO/CAP 2018 criteria based on local testing on the most recent analyzed biopsy.
Disqualifiers
Patients with pathological complete response (pCR) after neoadjuvant treatment.
Any concurrent or planned treatment for the current diagnosis of BC other than adjuvant ET except for denosumab or zoledronic acid, which are allowed.
Diagnosis of an alternative cancer in the five years prior to primary BC diagnosis other than for non-melanoma carcinoma of the skin or cervical carcinoma in situ. Other stage I tumors will be discussed case by case prior to inclusion with the Medical Monitor of the Study.
Active or prior documented inflammatory bowel disease (i.e., Crohn's disease, ulcerative colitis, or a preexisting chronic condition resulting in baseline grade ≥1 diarrhea) that may significantly alter the absorption of oral drugs.
Trial design
Design model
Sequential
Treatments tested in this trial
Giredestrant
DrugGiredestrant is a highly potent, non-steroidal, oral selective ER antagonist and degrader (SERD)
Abemaciclib
DrugAbemaciclib is an orally administered CDK4/6 inhibitor
Inavolisib
DrugInavolisib is a potent, selective inhibitor of the Class I phosphatidylinositol 3-kinase α (PI3K-alpha isoform (p110-alpha)
Treatment groups
976 Participants
are divided into 4 treatment groupsGroup A: Arm A: Control ArmNo intervention 0 interventions
Group B: Arm B: Experimental Arm with giredestrantExperimental treatment 1 intervention
Group C: Arm C: Experimental Arm with giredestrant + abemaciclibExperimental treatment 2 interventions
Group D: Arm D: Experimental Arm with giredestrant + inavolisibExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Evaluation of decrease or clearance in baseline ctDNA at three months after initiation of study treatment
To evaluate the treatment efficacy -in terms of rate of patients with a 90% decrease or clearance in baseline ctDNA at three months- of the different arms.
Time frame
Treatment phase (three months after treatment initiation)Secondary outcomes
1
Total ctDNA detection and breakdown by incidence at first ctDNA test versus incidence at subsequent ctDNA tests.
To assess the incidence of ctDNA detection in patients with HR-positive/HER2-negative breast cancer.
Time frame
Surveillance phase (up to two years after study start date)2
Proportion of patients with at least a 90% decrease in baseline ctDNA at six, nine, and 12 months after initiation of study treatment.
To evaluate the treatment efficacy -in terms of a 90% decrease in baseline ctDNA at six, nine, and 12 months- of the different experimental arms.
Time frame
Treatment phase (at six, nine, and 12 months after study treatment initiation)3
Proportion of patients with at least a 90% decrease in baseline ctDNA at three months maintained at six months and 12 months after initiation of study treatment.
To evaluate the treatment efficacy -in terms of a 90% decrease in baseline ctDNA at three months and maintained at six months and 12 months- of the different treatment arms.
Time frame
Treatment phase (at six and 12 months after study treatment initiation)4
Proportion of patients with 50% and 70% decrease in baseline ctDNA at three, six, nine, and 12 months after initiation of study treatment.
To evaluate the treatment efficacy -in terms of a 50% and 70% decrease in baseline ctDNA at three, six, nine, and 12 months- of the treatment different arms.
Time frame
Treatment phase (at three, six, nine, and 12 months after study treatment initiation) Source ClinicalTrials.gov