Study to evaluate treatment efficacy by monitoring minimal residual disease in an early breast cancer populatio
- Conditions
- Early breast cancerCancer
- Registration Number
- ISRCTN50261938
- Lead Sponsor
- Medica Scientia Innovation Research, S.L. (MEDSIR)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 1260
Surveillance phase:
1. Signed ICF prior to participation in any study-related activities
2. Male or female patients aged 18 years or older
3. ECOG 0 or 1
4. 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
5. Patients with high-risk early-stage BC according to at least one of the following criteria:
5.1. If no previous neoadjuvant chemotherapy:
5.1.1. pN2/N3 or
5.1.2. pN1,1. pT3/T4 and/or
5.2. High genomic risk defined as Oncotype Dx Recurrence Score > 25 if postmenopausal;> 20 if pre-menopausal, Prosigna score = 41, Mammaprint high risk category or similar and/or
5.3. Histological grade II/III and proliferation marker Ki67 (Ki67) >20%
5.3.1. If patients have received previous neoadjuvant chemotherapy, they must have had significant residual invasive disease defined as at least one of the following:
5.3.1.1. Residual invasive disease in the breast ypT3 or ypT4 and/or
5.3.1.2. Any macroscopic, =2 mm, residual lymph node involvement regardless of primary tumor site involvement (includes no residual disease in the breast)
6. On adjuvant treatment with ET for at least 2 years and no more than four years at the time of study enrolment with an additional three years of ET planned. At least 12 months prior to enrolment on the same ET treatment with AI or tamoxifen (LHRH for pre-menopausal women and men is required). Note: Male and pre-menopausal patients treated with tamoxifen alone are excluded
7. No prior treatment with CDK4/6 inhibitors
8. No prior treatment with fulvestrant
9. 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
10. Absence of metastatic disease by routine clinical assessment (computed tomography [CT] scan of the thorax and abdomen, and bone scan) confirmed no longer than 3 months prior to study inclusion
11. Patients must have had surgery for their primary BC with documented clear margins (as per local guidelines) within the past 5 years
12. Patients must be able and willing to adhere to study procedures.
Treatment phase:
1. Signed ICF prior to study inclusion
2. ctDNA positivity with no evidence of clinical or radiologic recurrence by standard assessments (e.g. breast ultrasound, staging scans, NMR)
3. ECOG 0, 1 or 2
4. Patients must have received the same ET during at least the last 12 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 pre-menopausal.
6. Female of reproductive potential and male patients 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
7. Resolution of all acute toxic effects of prior anti-cancer therapy to Grade =1 as determined by the NCI-CTCAE v 5.0
8
Surveillance phase:
1. Any concurrent or planned treatment for the current diagnosis of BC other than adjuvant ET
2. Diagnosis of an alternative cancer in the five years prior to primary BC diagnosis other than for nonmelanoma 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
3. 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
4. Active cardiac disease or history of cardiac dysfunction including any of the following:
4.1. History (within 2 years from screening) or presence of idiopathic bradycardia or resting heart rate <50 beats per minute at screening
4.2. History of angina pectoris or symptomatic coronary heart disease within 12 months prior to study entry
4.3. 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
4.4. History or presence of an abnormal ECG that is clinically significant in the investigator’s opinion
4.5. 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
5. History of pneumonitis, ILD, or pulmonary fibrosis
6. Known history of Human Immunodeficiency Virus (HIV) infection (testing not required as part of study screening)
7. 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
8. 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 DVT. Low molecular weight heparin (LMWH), low-dose aspirin or clopidogrel are permitted
9. Creatinine clearance <30 mL/min
10. Participants with renal dysfunction who require dialysis
11. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator’ opinion cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol
12. Females who are known to be breastfeeding or pregnant as determined by a serum pregnancy test human chorionic gonadotropin (ß-HCG) prior to the administration of any trial treatment. Since ß-HCG overexpression can be also elevated in some tumor types, a positive result should be confirmed with a validated alternative test (e.g., ultrasound)
13. Female or male participants planning a pregnancy
Treatment phase:
1. Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances
2. Undergoing any other simultaneous anti-cancer treatment since enrolling in the study, other than hormonal therapy or a bisphosphonate (or denosumab
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Efficacy measured using a comparison of ctDNA levels, expressed as the proportion of patients with at least a 90% decrease or clearance of the baseline ctDNA ,at 3 months after initiation of study treatment
- Secondary Outcome Measures
Name Time Method