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AzTrials

Breast CancerPhase 2MiRaDoRNCT05708235

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

A Phase 2 study testing Giredestrant, Abemaciclib and Inavolisib in people with Breast Cancer, run by MedSIR at 41 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Giredestrant, Abemaciclib and Inavolisib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
976 participants
Where
41 sitesin 2 countries
Study dates
1 Apr 2024to 30 Jun 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed surveillance phase ICF prior to participation in any Study-related activities.
  • Male or female participants 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/College of American Pathologists (ASCO/CAP) 2020 guidelines and HER2-negative BC as per ASCO/CAP 2018 criteria based on local testing on the most recent analyzed biopsy.
  • Participants with high-risk early-stage BC according to at least one of the following criteria:
  • If no previous neoadjuvant chemotherapy:
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  • pN2-N3, or ii. pN1 (including micrometastasis - pN1mi) if:
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  • pT3/T4, or
  • pT2 and high genomic risk, and/or histological grade III, and/or Ki 67 ≥ 30%. b. If participants 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/T4, or
  • cT2 and high genomic risk, and/or histological grade III, and/or Ki67 ≥ 30%. Note: Genomic risk using platforms such as Oncotype Dx, Prosigna or Mammaprint won't be assessed for the screening to participate in the Study. However, participants with the detailed scores assessed prior to Study inclusion, may be eligible.
  • 6. 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 six months prior to enrolment on the same ET treatment with AI or tamoxifen (LHRH agonist is mandatory for male and premenopausal participants receiving AI or tamoxifen, except in cases of bilateral oophorectomy).
  • Note: Premenopausal and male participants treated with tamoxifen alone are excluded.
  • 7. Prior treatment with cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) in the adjuvant setting will be allowed in the case of an interval of at least 12 months between the last dose and inclusion in the trial.
  • 8. No prior treatment with selective estrogen receptor degraders (SERDs) will be allowed.
  • 9. Availability and willingness to provide the most recently available (archival formalin-fixed paraffin-embedded [FFPE]) tumor tissue sample (either from diagnostic biopsy, primary surgery, or where available from a residual disease post-neoadjuvant therapy) at the time of Study inclusion.
  • Note I: Participants 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.
  • Note II: Participants with bilateral carcinoma of the breast may be included as long as at least one of the tumors meets the criteria established by the protocol and both are HR-positive and HER2-negative tumors.
  • 10. Successful ctDNA assay designability, defined as the ability to generate a personalized, tumor-informed ctDNA assay based on sequencing of tumor tissue and matched germline DNA, enabling longitudinal ctDNA assessment.
  • 11. Absence of metastatic disease by routine clinical assessment (computed tomography [CT] scan of the thorax and abdomen, and bone scan or positron emission tomography [PET] scan) confirmed no longer than three months prior to Study inclusion.
  • 12. Participants 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).
  • 13. Participants must be able and willing to adhere to Study procedures.
  • Inclusion criteria for direct-to-treatment-phase entry:
  • Participants who have not participated in the molecular surveillance phase but have a positive ctDNA test (conducted under other circumstances) will be considered eligible to enter to the treatment phase directly if they fulfill all the inclusion criteria listed below:
  • Signed treatment phase ICF prior to participation in any Study-related activities.
  • Male or female participants aged 18 years or older.
  • Histologically proven primary HR-positive according to the updated ASCO/CAP 2020 guidelines and HER2-negative BC as per ASCO/CAP 2018 criteria based on local testing on the most recent analyzed biopsy.
  • Availability and willingness to provide the most recently available (archival FFPE) tumor tissue sample (either from diagnostic biopsy, primary surgery, or where available from a residual disease post-neoadjuvant therapy) at the time of Study inclusion.
  • Note I: Participants 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.
  • Note II: Participants with bilateral carcinoma of the breast may be included as long as at least one of the tumors meets the criteria established by the protocol and both are HR-positive and HER2-negative tumors.
  • 5. Successful ctDNA assay designability, defined as the ability to generate a personalized, tumor-informed ctDNA assay based on sequencing of tumor tissue and matched germline DNA, enabling longitudinal ctDNA assessment.
  • 6. Confirmation of ctDNA positivity by the Study test. Note: Only participants who are confirmed as ctDNA-positive by the SignateraTM Genome test will be eligible to enter the treatment phase. External ctDNA results may be used to identify potential candidates, but eligibility will be based solely on the ctDNA status determined by the SignateraTM Genome test.
  • 7. Participants 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).
  • 8. Fulfillment of all general treatment phase eligibility criteria listed below.
  • 9. No participation in another interventional clinical trial within 28 days prior to screening or concurrent participation in another interventional clinical trial.
  • Inclusion criteria for all participants to treatment phase entry:
  • Participants will be considered eligible to enter to the treatment phase if they fulfill all the eligibility criteria listed below:
  • General inclusion criteria for all Study arms:
  • 1. Signed treatment phase ICF prior to participation in any Study treatment phase-related activities.
  • 2. ctDNA positivity with no evidence of locoregional or contralateral clinical or radiologic recurrence by standard assessments (breast staging scans, e.g.: mammogram, breast ultrasound, breast magnetic resonance imaging [MRI]).
  • 3. ECOG performance status 0 or 1. 4. 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. Participants must have received the same ET treatment with AI or tamoxifen during at least the last six months. A temporary discontinuation of < 90 days during the surveillance phase is allowed.
  • 5. Receiving LHRH agonist therapy alongside the same ET treatment for at least 90 days prior to initiation of one of the available Study treatments if male or premenopausal female participant.
  • 6. Prior treatment with CDK4/6i in the adjuvant setting will be allowed in the case of an interval of at least 12 months between the last CDK4/6i dose and Study inclusion in the trial.
  • 7. No prior treatment with SERDs will be allowed. 8. Female of reproductive potential and male participants with female partners of childbearing potential, must remain abstinent and truly abstain from sexual activity (refrains from heterosexual intercourse) or use locally recognized adequate methods of contraception (described as that with a failure rate < 1%) for the duration of trial treatment. In addition, participants must follow these guidelines for a certain period of time after the last dose of trial treatment, specified in the protocol depending on which treatment arm the participant is allocated in.
  • During this period of time, female and male participants must as well refrain from donating eggs or sperm.
  • Note: Female participants will be deemed not of childbearing potential if they are postmenopausal or have had irreversible sterilization. Well-defined premenopausal status refers to women who have not reached the postmenopausal state because they are not permanently infertile due to prior bilateral oophorectomy, age ≥ 60 years or age < 60 years with amenorrhea for ≥ 12 months and estradiol and follicle-stimulating hormone (FSH) levels in the postmenopausal range.
  • 9. Resolution of all acute toxic effects of prior anti-cancer therapy to Grade ≤ 1 as determined by the National Cancer Institute - Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v.5.0) (except for alopecia, or other toxicities not considered a safety risk for the participant at investigator's discretion). Adverse events (AEs) of current ET treatment are not included.
  • 10. Adequate hematologic and organ function within 14 days before the first Study treatment on Day 1 of Cycle 1, defined by the following:
  • Hematological (without platelet, red blood cell (RBC) transfusion, and/or granulocyte colony-stimulating factor support within seven days before first Study treatment dose): White blood cell (WBC) count > 3.0 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100.0 x109/L, and hemoglobin ≥ 9.0 g/dL (≥ 5.6 mmol/L).
  • Hepatic: Serum albumin ≥ 3 g/dL; Bilirubin ≤ 1.5x the upper limit of normal (ULN) (≤ 3x ULN in the case of Gilbert's disease); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5x ULN; alkaline phosphatase (ALP) ≤ 2 × ULN.
  • Renal: serum creatinine level ≤ 1.5x the ULN or an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m², as calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation (National Kidney Foundation [NKF], 2021).
  • Note: eGFR should be determined using the recommended standardized 2021 CKD-EPI Creatine Equation (without race adjustment):
  • eGFR (mL/min/1.73 m²) = 142 × min (Scr/κ, 1) ^α × max (Scr/κ, 1) ^-1.200 × 0.9938^Age × 1.012 [if female].
  • Scr = serum creatinine in mg/dL, κ = 0.7 for females; 0.9 for male; α = -0.241 for females; -0.302 for males; min (Scr/κ, 1) = the lesser of Scr/κ or 1; max (Scr/κ, 1) = the greater of Scr/κ or 1; Age = age in years; The multiplication factor 1.012 is applied only for females.
  • 11. Participants who are able and willing to swallow, retain, and absorb oral medication.
  • 12. Participants must be able and willing to adhere to Study procedures.
  • Additional inclusion criteria for Arm C (giredestrant + abemaciclib arm):
  • Participants with prior diagnosis of thrombosis might be included as long as they are under stable anti-coagulation regimen therapy 28 days prior to starting treatment with abemaciclib.
  • Additional inclusion criteria for Arm D (giredestrant + inavolisib arm):
  • 1. Central confirmation of biomarker eligibility (detection of specified PIK3CA mutation(s) via Qiagen therascreen® PIK3CA RGQ PCR kit [CE-IVD]) in tumor tissue sample.
  • 2. No prior treatment with any phosphatidylinositol 3-kinase (PI3K), Akt, or mammalian target of rapamycin (mTOR) inhibitors, or any agent whose mechanism of action is to inhibit the PI3K/Akt/mTOR pathway.

Who cannot join

  • Participants with pathological complete response (pCR) after neoadjuvant treatment.
  • Receiving or planning to receive any concurrent anti-cancer treatment for the current BC diagnosis, other than permitted adjuvant ET and/or bone-modifying agents (denosumab or biphosphonates).
  • 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.
  • 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.
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  • 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, e. 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.
  • Clinically significant liver disease consistent with Child-Pugh C, including current known infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), current alcohol abuse, or cirrhosis. Participants with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • 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.
  • Participant who has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator' opinion cause unacceptable safety risks, contraindicate participation in the clinical trial or compromise compliance with the protocol.
  • Females who are known to be breastfeeding or pregnant as determined by a serum pregnancy test, Human chorionic gonadotropin (β-HCG), prior to the administration of any trial treatment (once during the treatment phase). Since β-HCG over expression can be also elevated in some tumor types, a positive result should be confirmed with a validated alternative test (e.g. ultrasound).
  • Female or male participants planning a pregnancy.
  • Participation in another interventional clinical trial within 28 days prior to screening or concurrent participation in another interventional clinical trial.
  • Eligibility criteria for participant entry into the treatment phase:
  • General exclusion criteria:
  • Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances.
  • Undergoing any concurrent anti-cancer treatment for the current BC diagnosis, other than permitted adjuvant ET and/or bone-modifying agents (denosumab or bisphosphonates).
  • Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 28 days of start of Study drug, or participants who have not recovered from the side effects of any major surgery.
  • Treatment with strong Cytochrome P450 3A4 (CYP3A4) inhibitors or strong CYP3A4 inducers within 14 days or five drug-elimination half-lives, whichever is longer, prior to initiation of Study treatment.
  • 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.
  • QTcF > 450 ms for women and > 470 ms for men by at least 3 ECGs > 30 minutes apart.
  • History or presence of an abnormal ECG that is clinically significant in the investigator's opinion, e. 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, ILD, or pulmonary fibrosis.
  • Known history of HIV infection.
  • Clinically significant liver disease consistent with Child-Pugh C, including current known infection with HBV or HCV, current alcohol abuse, or cirrhosis. Participants with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive HBcAb test, accompanied by a negative HBV DNA test) are eligible. Participants positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
  • 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.
  • Females who are known to be breastfeeding or pregnant as determined by a serum pregnancy test (β-HCG) prior to the administration of any trial treatment (once during the treatment phase). Since β-HCG over expression can be also elevated in some tumor types, a positive result should be confirmed with a validated alternative test (e.g. ultrasound).
  • Participant who has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator' opinion cause unacceptable safety risks, contraindicate participation in the clinical trial or compromise compliance with the protocol.
  • Participant has a history of non-compliance to medical regimen.
  • Additional exclusion criteria for Arm D (giredestrant + inavolisib):
  • 1. Type 2 diabetes requiring ongoing systemic treatment at the time of Study entry; or any history of Type 1 diabetes.
  • 2. Fasting glucose ≥ 126 mg/dL or ≥ 7.0 mmol/L and hemoglobin A1c (HbA1c) ≥ 6.0%.
  • 3. Any concurrent ocular or intraocular condition excluding cataracts (e.g. diabetic retinopathy) that, in the opinion of the investigator, would require medical or surgical intervention during the Study period to prevent or treat vision loss that might result from that condition.
  • 4. Active inflammatory (e.g. uveitis or vitritis) or severe infectious conditions (e.g. keratitis, scleritis, or endophtalmitis) in either eye or history of idiopathic or autoimmune-associated uveitis in either eye.

Trial locations and contacts

41 sites in 2 countries.

41 sites in 2 countries

Spain37 sites

  • Complejo Hospitalario Universitario A Coruña (CHUAC)

    A Coruña

  • Hospital General Universitario Dr. Balmis

    Alicante

  • Hospital Marina Salud de Denia

    Alicante

  • Hospital Virgen de los Lirios

    Alicante

  • Fundació Althaia

    Barcelona

  • Hospital Clínic i Provincial de Barcelona

    Barcelona

  • Hospital Universitari Dexeus

    Barcelona

  • Hospital Universitario de Basurto

    Bilbao

  • Hospital Provincial de Castellón

    Castellon

  • Hospital Universitario Reina Sofía

    Córdoba

  • Hospital del Vinalopó

    Elche

  • Institut Català d' Oncologia Girona (ICO)

    Girona

  • Hospital Universitario Clínico San Cecilio de Granada

    Granada

  • Complejo Hospitalario de Jaén

    Jaén

  • Hospital Universitario de León

    León

  • Hospital Universitario Arnau de Vilanova de Lleida

    Lleida

  • Clínica Universidad de Navarra

    Madrid

  • Hospital Beata María Ana

    Madrid

  • Hospital Universitario de Torrejón

    Madrid

  • Hospital Universitario Doce de Octubre

    Madrid

  • Hospital Universitario La Paz

    Madrid

  • Hospital Universitario Sanchinarro-START-CIOCC

    Madrid

  • Hospital Regional Universitario de Málaga (Hospital Carlos Haya)

    Málaga

  • Hospital Universitario Virgen de la Victoria

    Málaga

  • Hospital Clínico Universitario Virgen de la Arrixaca

    Murcia

  • Hospitalario Universitario de Navarra

    Pamplona

  • Hospital de Sagunto

    Sagunto

  • Hospital Quirónsalud Sagrado Corazón

    Seville

  • Hospital Universitario Virgen del Rocío

    Seville

  • Hospital Universitari Sant Joan de Reus

    Tarragona

  • Hospital Arnau de Vilanova de Valencia

    Valencia

  • Hospital Clínico Universitario de Valencia

    Valencia

  • Hospital Universitari i Politècnic La Fe

    Valencia

  • Hospital Universitario La Ribera, Alzira

    Valencia

  • Complejo Hospitalario Universitario de Vigo

    Vigo

  • Hospital de Xativa

    Xàtiva

  • Hospital Universitario Miguel Servet

    Zaragoza

Other trials in Spain

United Kingdom4 sites

  • University Hospital Coventry

    Coventry

  • Royal Surrey County Hospital NHS Foundation Trust

    Guildford

  • Barts Cancer Institute

    London

  • Imperial College Healthcare NHS Trust

    London

Other trials in United Kingdom

About this study

Official title: A Proof of Concept Study to Evaluate Treatments' Efficacy by Monitoring Minimal Residual Disease Using ctDNA in HR-positive/HER2-negative Early Breast Cancer Population

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).

Read more

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.

Read the detailed description

This is a multicenter, open-label, non-comparative, phase II, biomarker-driven adjuvant treatment Study. Men and pre- and postmenopausal women aged ≥ 18 years with early stage HR-positive/HER2-negative BC at high risk of relapse, but with no evidence of locoregional, contralateral, or distant disease, who have undergone surgery, have received radiotherapy if indicated as per local guidelines and are on adjuvant treatment with endocrine therapy (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 six months prior to enrolment on the same ET with aromatase inhibitors (AI) or tamoxifen (luteinizing hormone-releasing hormone [LHRH] agonist is mandatory for male and premenopausal participants receiving AI, as well as for premenopausal participants treated with tamoxifen, except in cases of bilateral oophorectomy).

Note: Premenopausal and male participants treated with tamoxifen alone are excluded.

After signing the ICF and confirmed eligibility, 976 participants will first enter the surveillance phase in which blood will be collected and analyzed to detect the presence or absence of ctDNA at predefined time points for longitudinal surveillance. ctDNA analysis will occur every three months from Study inclusion during the first year and every six months thereafter until end of surveillance phase, which is defined as ctDNA positive result, permanent discontinuation (or temporally discontinuation ≥ 90 days) of the adjuvant hormonal treatment, or the end of accrual of the treatment phase upon Steering Committee decision, whichever occurs first.

Surveillance phase participants should be followed up in line with standard practice every six months (± two weeks) to assess for disease recurrence.

Participants should continue to receive ET according to standard treatment (with tamoxifen or AI [letrozole, anastrozole, exemestane]); the use of LHRH agonist treatment is mandatory for male and premenopausal participants receiving either AI or tamoxifen , except in cases of bilateral oophorectomy. Changes in ET during the ctDNA surveillance period are generally not allowed, however, justified changes such as anastrozole and letrozole switch may be discussed with the Medical Monitor. Changes in LHRH agonist treatment may also be discussed with the Medical Monitor. Participants who permanently discontinue or temporally discontinued (≥ 90 days) standard ET during the surveillance phase are not eligible to enter the treatment phase of the Study.

Following completion of surveillance phase, participants who were not allocated in any arm will continue to be followed up in line with standard practice outside of the trial, and the collection of samples for ctDNA analysis will be halted.

Note: Participants who had not participated in the surveillance phase but have a positive ctDNA test (conducted under other circumstances) will be eligible for direct-to-treatment phase entry if they fulfill all the matching eligibility requirements. Therefore, these participants will not need to meet all the eligibility criteria for the surveillance phase.

Upon confirmed eligibility, a total of 40 participants will be allocated to four treatment arms as follows:

Arm A: Experimental Arm with the same standard ET that was prescribed during the surveillance phase for a period of 90 days, followed by change in treatment to giredestrant, giredestrant plus abemaciclib or giredestrant plus inavolisib, as determined by the investigator´s choice (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).

Note I: In addition to the treatments described on each of the treatment arms, LHRH agonist will be administered to male participants and premenopausal participants according to local prescribing information. The participant should be supplied with the previous LHRH agonist they were taking.

Note II: During the length of the Study, additional treatment arms may be opened to stay up to date with the most recent advances in oncology, and to be able to provide the best treatment options to participants in this Study.

Note III: For participants eligible to receive inavolisib with a creatinine clearance between 30 and < 60 mL/min, as estimated by the 2021 CKD-EPI Creatinine Equation (NKF, 2021), the starting dose is 6 mg orally once daily (PO QD) on Days 1-28 of each 28-day cycle.

After allocation, serial assessment of ctDNA will be continuously performed every three months during the first year and every six months thereafter until end of treatment (EoT) to correlate any ctDNA variations with response. These data will also be used to confirm feasibility of eventual arm extensions, with maximum two arms that could be expanded across the four experimental arms. The expansion will be approved when the arm complies with the following criteria:

  • If at three months, a 90% ctDNA decrease is observed in at least 30% participants and if after three additional months, a 90% ctDNA decrease/clearance is maintained in at least 20% participants.

In this case, 10 additional participants will be enrolled in the selected experimental arm (being completed with a total of 20 participants).

  • If all experimental arms fulfill these criteria, the two arms with the highest proportion of participants with 90% ctDNA decrease will be the ones expanded.
  • If cohorts remain too similar (no clear "winners"), the decision will be taken by the Steering Committee based on the duration of the response and the safety and toxicity of each specific treatment.
  • If none of the arms fulfill the specific expansion criteria, the Steering Committee will further evaluate the data and may nominate the two arms with the strongest signal of ctDNA decrease for further expansion.

If the strategy of ctDNA monitoring permits to identify participants at high risk of relapse and to assess whether treatment at molecular relapse can improve outcome, potentially new cohorts may be added.

Note: In addition, a maximum of two arms could be expanded, depending on the number of participants with PIK3CAmut tumors included in arms B and C. In this case, up to 10 participants (maximum of five participants per arm) with these mutations may be added to the specific treatment arms in order to have a similarly balanced background in terms of PIK3CA mutational status (i.e., a comparable distribution of participants with PIK3CAmut and PIK3CAwt tumors across treatment arms) (as an extension), depending on the Steering Committee decision, and if specific criteria to extend those cohorts are fulfilled.

The amended CSP will be resubmitted to the pertinent regulatory agencies for approval of every arm extension and/or new arm addition

After treatment discontinuation (EoT), all participants will have a safety visit scheduled 28 days (± 7 days) after the last dose of Study treatment, in order to follow up toxicities and changes in concomitant medication.

After the safety visit, all participants will enter a post treatment follow-up period during which survival status and subsequent anticancer therapy information will be collected every 3 months (± 7 days) until death, lost to follow-up, elective withdrawal from the Study, or the EoS, whichever occurs first. This information may be collected by telephone call.

Participants who discontinue treatment without evidence of disease recurrence will be followed for tumor assessments (according to the planned schedule before treatment discontinuation) until documented recurrence, elective withdrawal from the Study, the start of new anti-cancer treatment, or Study completion or termination.

Conditions
Breast Cancer
Being tested
Giredestrant, Abemaciclib, Inavolisib, Standard ET followed by change in treatment
Keywords
ctDNA, Early breast cancer, HR-positive/HER2-negative, MRD, Minimal Residual Disease
Medical subject headings
Breast Neoplasms, Neoplasm, Residual

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GiredestrantDrug

    Also called GDC-9545

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

  • AbemaciclibDrug

    Also called LY2835219

    Abemaciclib is an orally administered CDK4/6 inhibitor

  • InavolisibDrug

    Also called GDC-0077

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

  • Standard ET followed by change in treatmentDrug

    90-day period of standard ET in accordance with standard clinical practice, followed by one of the other three predefined treatments (giredestrant, giredestrant plus abemaciclib or giredestrant plus inavolisib if a detectable PIK3CA mutation is present and the participant also meets all additional eligibility criteria for Arm D).

Study groups in NCT05708235
Study groupRoleWhat they receive
Arm A: Control ArmActive comparatorParticipants assigned to this arm 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. After this 90-day period, participants will be eligible to receive one of the other three predefined treatments (giredestrant, giredestrant plus abemaciclib or giredestrant plus inavolisib if a detectable PIK3CA mutation is present and the participant also meets all additional eligibility criteria for Arm D). as determined by the investigator´s choice. No changes to the prescribed ET are permitted during the 90-day period.
Receives: Drug: Standard ET followed by change in treatment
Arm B: Experimental Arm with giredestrantExperimentalGiredestrant: 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).
Receives: Drug: Giredestrant
Arm C: Experimental Arm with giredestrant + abemaciclibExperimentalGiredestrant: 30 mg will be taken PO 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). Abemaciclib 150 mg 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). Note: Participants who have previously received adjuvant abemaciclib at a reduced dose (100 mg BID or 50 mg BID) due to toxicity may initiate study treatment at the same reduced dose level, at the investigator's discretion. Dose re-escalation is not permitted.
Receives: Drug: Giredestrant; Drug: Abemaciclib
Arm D: Experimental Arm with giredestrant + inavolisibExperimentalGiredestrant: 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).
Receives: Drug: Giredestrant; Drug: Inavolisib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Evaluation of decrease or clearance in baseline ctDNA at three months after initiation of study treatment

    To evaluate the efficacy - in terms of rate of participants with a 90% decrease or clearance in baseline ctDNA at three months - of the different arms

    Measured: Treatment phase (three months after Study treatment initiation)

Secondary outcomes (8)

  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.

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

  2. Proportion of participants 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.

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

  3. Proportion of participants 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.

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

  4. Proportion of participants 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.

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

  5. Time to rising ctDNA defined as time to first ctDNA increase compared to baseline

    To evaluate the treatment efficacy -in terms of time to rising ctDNA during the study follow-up- of the different arms.

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

  6. Duration of at least a 90% decrease in baseline ctDNA after initiation of study treatment.

    To evaluate the duration of treatment efficacy -in terms of time with at least a 90% decrease in baseline ctDNA- of the treatment different arms.

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

  7. Best percentage of ctDNA decrease relative to baseline at six, nine, and 12 months after initiation of study treatment.

    To evaluate the ctDNA decrease relative to baseline -at three, six, nine, and 12 months- of the different arms.

    Measured: Treatment phase (up to five years)

  8. Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0.

    National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 will performed to evaluate the safety and tolerability of the different treatments. The occurrence and maximum grade of AEs observed throughout the study will be listed and tabulated according to type and dose level. Any AEs that the investigator reports as unrelated to the drug will also be reported. In this study, side effects will be assessed according to the NCI-CTCAE v.5.0.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2023
  2. Study start1 Apr 2024
  3. Primary completion30 Jun 2028 (estimated)
  4. Study completion30 Jun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
976 HR+, HER2-, early BC participants on ET adjuvant treatment will be screened; 40 participants with ctDNA positivity will be allocated to one of four arms: 1. Arm A (participants with PIK3CAwt tumors, or participants with PIK3CAmut tumors that do not fulfill the specific criteria to enter arm D) and arm D (participants with PIK3CAmut tumors that fulfill the specific criteria to enter arm D). 2. Once arm A is closed, participants will be included in arm B (\*). 3. Once arms A and B are closed, participants will be included in arm C (\*). * Participants with PIK3CAwt tumors, or participants with PIK3CAmut tumors that do not fulfill the specific criteria to enter arm D. Also, participants with PIK3CAmut tumors that fulfill the specific criteria to enter arm D, once arm D is completed.
Masking
None (open label)
Enrolment
976 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05708235
Sponsor's protocol ID
MedOPP485
Other IDs
2023-505661-89-00, 2023
Acronym
MiRaDoR
Status last verified
Sep 2026
First submitted
12 Jan 2023
Last updated
24 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Giredestrant, Abemaciclib and Inavolisib in people with Breast Cancer, run by MedSIR at 41 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 63 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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 Study treatment initiation)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05708235.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.

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