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

NCT05708235 | Recruiting Phase 2 DMC

• 2 other identifiers: MedOPP4852023-505661-89-00
• Study Type: interventional
• Target: 976
• Locations: 2 countries
• Sites: 41

Brief Summary

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.

Conditions

Breast Cancer

Keywords

ctDNA; Early breast cancer; HR-positive/HER2-negative; MRD; Minimal Residual Disease

Outcome Measures

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.

  Treatment phase (three months after treatment initiation)

Secondary Outcomes (8)

• Total ctDNA detection and breakdown by incidence at first ctDNA test versus incidence at subsequent ctDNA tests.

  Surveillance phase (up to two years after study start date)

• Proportion of patients with at least a 90% decrease in baseline ctDNA at six, nine, and 12 months after initiation of study treatment.

  Treatment phase (at six, nine, and 12 months after study treatment initiation)

• 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.

  Treatment phase (at six and 12 months after study treatment initiation)

• Proportion of patients with 50% and 70% decrease in baseline ctDNA at three, six, nine, and 12 months after initiation of study treatment.

  Treatment phase (at three, six, nine, and 12 months after study treatment initiation)

• Time to rising ctDNA defined as time to first ctDNA increase compared to baseline

  Treatment phase (up to five years after study treatment initiation)

Study Arms (4)

Arm A: Control Arm

NO INTERVENTION

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.

Arm B: Experimental Arm with giredestrant

EXPERIMENTAL

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).

Drug: Giredestrant

Arm C: Experimental Arm with giredestrant + abemaciclib

EXPERIMENTAL

* 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).

Drug: Giredestrant; Drug: Abemaciclib

Arm D: Experimental Arm with giredestrant + inavolisib

EXPERIMENTAL

* 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).

Drug: Giredestrant; Drug: Inavolisib

Interventions

Giredestrant DRUG

Giredestrant is a highly potent, non-steroidal, oral selective ER antagonist and degrader (SERD)

Also known as: GDC-9545

Arm B: Experimental Arm with giredestrant; Arm C: Experimental Arm with giredestrant + abemaciclib; Arm D: Experimental Arm with giredestrant + inavolisib

Abemaciclib DRUG

Abemaciclib is an orally administered CDK4/6 inhibitor

Also known as: LY2835219

Arm C: Experimental Arm with giredestrant + abemaciclib

Inavolisib DRUG

Inavolisib is a potent, selective inhibitor of the Class I phosphatidylinositol 3-kinase α (PI3K-alpha isoform (p110-alpha)

Also known as: GDC-0077

Arm D: Experimental Arm with giredestrant + inavolisib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients with high-risk early-stage BC according to at least one of the following criteria: a. If there is no previous neoadjuvant chemotherapy: i. pN2-N3 or ii. pN1 (including micrometastasis - pN1mi) if:
• \. pT3-T4, or 2. pT2 and high genomic risk and/or histological grade III and/or Ki 67≥30%. b. If patients have received previous neoadjuvant chemotherapy, they must have had residual invasive disease defined as at least one of the following: i. Residual invasive disease in lymph nodes (ypN+, including ypN1mi) ii. ypN0 with residual invasive disease in breast if:
• cT3-4, or
• \. On adjuvant treatment with ET for at least two years and no more than seven years at the time of Study enrolment with an additional three years of ET planned, and at least 6 months prior to enrolment on the same ET treatment with AI or tamoxifen (LHRH is mandatory for men and premenopausal women receiving AI, as well as for premenopausal women treated with tamoxifen, except in cases of bilateral oophorectomy.) Note: Pre-menopausal patients treated with tamoxifen alone are excluded.
• \. No prior treatment with SERDs will be allowed.
• \. Willingness and ability to provide tissue from one archival tumor tissue sample (either from diagnostic biopsy, primary surgery, or where available from a residual disease post-neoadjuvant therapy).
• Note: Patients with multifocal BC may be enrolled, if archival tissue samples from at least two tumors are available and after histopathological examination, all tumors meet pathologic criteria for HR-positive and HER2-negative BC.
• \. Patients must have had surgery for their primary BC with documented clear margins (as per local guidelines) and they must have received radiotherapy if indicated (as per local guidelines).
• \. Patients must be able and willing to adhere to Study procedures.

You may not qualify if:

• 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.
• 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.
• Active cardiac disease or history of cardiac dysfunction including any of the following:
• History (within two years from screening) or presence of idiopathic bradycardia or resting heart rate \<50 beats per minute at screening.
• History of angina pectoris or symptomatic coronary heart disease within 12 months prior to Study entry.
• QT interval corrected through use of Fridericia's formula (QTcF) \> 450 ms for women and \> 470 ms for men by at least three electrocardiograms (ECGs) \> 30 minutes apart.
• History or presence of an abnormal ECG that is clinically significant in the investigator's opinion,
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy cardiomyopathy, infiltrative cardiomyopathy, moderate-to-severe valve disease), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of long QT syndrome within 12 months.
• History of pneumonitis, interstitial lung disease (ILD), or pulmonary fibrosis.
• Known history of Human Immunodeficiency Virus (HIV) infection (testing not required as part of Study screening).
• Clinically significant liver disease consistent with Child-Pugh C, including active hepatitis (e.g., hepatitis B virus \[HBV\] or hepatitis C virus \[HCV\]), current alcohol abuse, cirrhosis, or positive test for viral hepatitis
• Active bleeding diathesis venous thrombo-embolism, previous history of bleeding diathesis, or chronic anti-coagulation treatment, or any indications or history of Disseminated Intravascular Coagulation (DIC) or Deep vein thrombosis (DVT). Low molecular weight heparin (LMWH), low dose aspirin or clopidogrel are permitted.
• Creatinine clearance \< 30mL/min.
• Participants with renal dysfunction who require dialysis.

Sponsors & Collaborators

• MedSIR: lead

Study Sites (41)

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, Spain

RECRUITING

Hospital General Universitario Dr. Balmis

Alicante, Spain

RECRUITING

Hospital Marina Salud de Denia

Alicante, Spain

RECRUITING

Hospital Virgen de los Lirios

Alicante, Spain

RECRUITING

Fundació Althaia

Barcelona, Spain

RECRUITING

Hospital Clínic i Provincial de Barcelona

Barcelona, Spain

RECRUITING

Hospital Universitari Dexeus

Barcelona, Spain

RECRUITING

Hospital Universitario de Basurto

Bilbao, Spain

RECRUITING

Hospital Provincial de Castellón

Castellon, Spain

RECRUITING

Hospital Universitario Reina Sofía

Córdoba, Spain

RECRUITING

Hospital del Vinalopó

Elche, Spain

RECRUITING

Institut Català d' Oncologia Girona (ICO)

Girona, Spain

RECRUITING

Hospital Universitario Clínico San Cecilio de Granada

Granada, Spain

RECRUITING

Complejo Hospitalario de Jaén

Jaén, Spain

RECRUITING

Hospital Universitario de León

León, Spain

RECRUITING

Hospital Universitario Arnau de Vilanova de Lleida

Lleida, Spain

RECRUITING

Clínica Universidad de Navarra

Madrid, Spain

RECRUITING

Hospital Beata María Ana

Madrid, Spain

RECRUITING

Hospital Universitario de Torrejón

Madrid, Spain

RECRUITING

Hospital Universitario Doce de Octubre

Madrid, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, Spain

RECRUITING

Hospital Universitario Sanchinarro-START-CIOCC

Madrid, Spain

RECRUITING

Hospital Regional Universitario de Málaga (Hospital Carlos Haya)

Málaga, Spain

RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, Spain

RECRUITING

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, Spain

RECRUITING

Hospitalario Universitario de Navarra

Pamplona, Spain

RECRUITING

Hospital de Sagunto

Sagunto, Spain

RECRUITING

Hospital Quirónsalud Sagrado Corazón

Seville, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, Spain

RECRUITING

Hospital Universitari Sant Joan de Reus

Tarragona, Spain

RECRUITING

Hospital Arnau de Vilanova de Valencia

Valencia, Spain

RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, Spain

RECRUITING

Hospital Universitari i Politècnic La Fe

Valencia, Spain

RECRUITING

Hospital Universitario La Ribera, Alzira

Valencia, Spain

RECRUITING

Complejo Hospitalario Universitario de Vigo

Vigo, Spain

RECRUITING

Hospital de Xativa

Xàtiva, Spain

RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, Spain

RECRUITING

University Hospital Coventry

Coventry, United Kingdom

RECRUITING

Royal Surrey County Hospital NHS Foundation Trust

Guildford, United Kingdom

RECRUITING

Barts Cancer Institute

London, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm, Residual

Interventions

giredestrant; abemaciclib; inavolisib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Antonio Llombart, MD

  Arnau de Vilanova Hospital, Valencia (Spain)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medsir

CONTACT

+34 932 214 135; contact.trials@medsir.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2023
• First Posted: February 1, 2023
• Study Start: April 1, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4); ES (37)