BridgeMD
TAILORswitch (PADA-2): rising ctDNA to tailor endocrine therapy switch in patients with ER+/HER2- metastatic breast cancer.
EU CTIS ID: 2025-524213-84-00
What this study is testing
To demonstrate the efficacy of the switch to camizestrant and abemaciclib in ER+ HER2- mBC participants receiving first line CDK4/6i and aromatase inhibitor who have displayed rising ctDNA with no evidence of disease progression
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- First written informed consent (ICF#1) prior to any trial specific procedures. When the participant is physically unable to give his written consent, an impartial witness, independent from the investigator and the sponsor, can confirm in signing the participant’s consent (Related to step 1)
- Additional written informed consent (ICF#3). When the participant is physically unable to give his written consent, an impartial witness independent from the investigator and the sponsor, can confirm in signing the participant’s consent (Related to step 2)
- Rising ctDNA (as defined in the protocol) detected during Step #1 (centrally determined);
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Having received at least 6 months of AI + CDK4/6i (Related to step 2)
- Adequate bone marrow reserve and organ function as follows: a) Hemoglobin ≥9.0g/dL (90 g/L). b) Absolute neutrophil count ≥1000/mm3 (1.0×10^9/L) or documented institutional normal range for starting abemaciclib. c) Total bilirubin ≤1.5×ULN or ≤3×ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia). d) ALT and AST ≤3×ULN; for participants with hepatic metastases, ALT and AST ≤5×ULN. e) Alkaline phosphatase ≤2.5×ULN (≤ 5.0×ULN if bone or liver metastases present). f) Serum creatinine ≤ 1.5×ULN or calculated creatinine clearance ≥ 30 mL/min as determined by Cockcroft-Gault (using actual body weight). (Related to step 2)
You likely can't join if
- Systemic antineoplastic therapy (except adjuvant therapies) received prior to AI and CDK4/6i
- Known leptomeningeal metastasis and/or brain metastasis
- Known contraindication to camizestrant and abemaciclib, per investigator assessment
- Prior exposure to camizestrant, other SERD or investigational endocrine therapy agents
- History of another malignancy, except (i) those treated with curative intent and with no known active disease ≥3 years; (ii) adequately treated non-melanoma cutaneous and in-situ cervix cancer
- Pregnant women or women who are breast-feeding or participants not willing to apply highly effective contraception as defined in the protocol
See the full eligibility criteria
Who can join
- First written informed consent (ICF#1) prior to any trial specific procedures. When the participant is physically unable to give his written consent, an impartial witness, independent from the investigator and the sponsor, can confirm in signing the participant’s consent (Related to step 1)
- Additional written informed consent (ICF#3). When the participant is physically unable to give his written consent, an impartial witness independent from the investigator and the sponsor, can confirm in signing the participant’s consent (Related to step 2)
- Rising ctDNA (as defined in the protocol) detected during Step #1 (centrally determined);
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Having received at least 6 months of AI + CDK4/6i (Related to step 2)
- Adequate bone marrow reserve and organ function as follows: a) Hemoglobin ≥9.0g/dL (90 g/L). b) Absolute neutrophil count ≥1000/mm3 (1.0×10^9/L) or documented institutional normal range for starting abemaciclib. c) Total bilirubin ≤1.5×ULN or ≤3×ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia). d) ALT and AST ≤3×ULN; for participants with hepatic metastases, ALT and AST ≤5×ULN. e) Alkaline phosphatase ≤2.5×ULN (≤ 5.0×ULN if bone or liver metastases present). f) Serum creatinine ≤ 1.5×ULN or calculated creatinine clearance ≥ 30 mL/min as determined by Cockcroft-Gault (using actual body weight). (Related to step 2)
- Female participants must have a negative highly sensitive serum pregnancy test during the screening period if they are of childbearing potential and agree to use highly effective contraceptive methods to prevent pregnancy during the study and for 4 weeks following the last dose of camizestrant (if applicable) and/or for 3 weeks after the last dose of CDK4/6inhibitor or must have evidence of nonchildbearing potential. In addition, female participants must refrain from egg cell donation and breastfeeding during this same period. a. Non-sterilized male partners of a participant who is a woman of childbearing potential must use a male condom plus spermicide from the time of screening throughout the total duration of the study until 28 days after last dose of camizestrant. b. Non-sterilised male participants (including males sterilised by a method other than bilateral orchidectomy, eg, vasectomy) who intend to be sexually active with a Female OfChildBearing Potential (FOCBP) must be using an acceptable method of contraception, such as male condom plus spermicide (condom alone in countries where spermicides are not approved), from enrolment throughout the study until at least 1 week to avoid conception during treatment. Male participants must not donate or bank sperm during this same period. c. Female partners (of child-bearing potential) of male participants enrolled in this study must also use a highly effective method of contraception from the time of study enrolment of their male partner, throughout their participation in the study, and until at least 1 week after their male partners last dose of camizestrant
- ER+ HER2- advanced (metastatic or locally advanced inoperable) breast adenocarcinoma (ERpositivity threshold: ≥10% tumor cells; HER2-negative tumour is defined as an immunohistochemical (IHC) score of 0 or 1+, or an IHC score of 2+ with negative in situ hybridization (ISH) (HER2/CEP17 ratio <2 or, for single probe assessment, HER2 copy number <4, according to the most recent available results), not amenable to resection or radiation therapy with curative intent;
- Eligible to (per investigator assessment) or currently receiving for up to 3 years, AI (+/- LH RH agonist) and CDK4/6i (palbociclib or ribociclib) as first line therapy with adequate cardiac, renal, hematological and hepatic functions per investigator assessment
- Evaluable disease (RECIST v1.1) before the start of AI+CDK4/6i and, in participants currently receiving AI and CDK4/6i, no evidence of clinical or radiological progression since AI+CDK4/6i initiation
- Must have an adequate archival tumor tissue sample available (with a cellularity > 30%) for centralized WGS analysis to design the ctDNA test. Requirements: • Sample age: Less than 10 years old. Preferably less than 2 years when possible • Preferred sample types (in order of priority): a) b) c) Most recent resected tumor tissue sample from primary breast site Affected lymph node with adequate cellularity. Metastatic tissue samples, including brain, lung, or other organs. Avoid bone samples.
- Women of childbearing potential must have a negative serum or urine pregnancy test done within 28 days before inclusion
- Pre/perimenopausal women and fertile men must agree to use adequate contraception methods during the study
- Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception until at least one week after the last treatment administration.
- Willingness and ability to comply with scheduled visits
- ctDNA detected at study entry and no rising ctDNA
- Minimum life expectancy of at least 6 months
- Participants must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan and other study procedures including follow-up
- Participants must be affiliated with a social security scheme or a beneficiary of such a scheme (or equivalent)
- Additional written informed consent (ICF#2). When the participant is physically unable to give his written consent, an impartial witness, independent from the investigator and the sponsor, can confirm in signing the participant’s consent (Sub Study)
- Participants must have received at least 6 months (from 22 weeks authorized) of treatment with AI + CDK4/6 inhibitor, with no evidence of ctDNA rising in STEP #1 (at the current visit or, if current results are pending, at the previous visit), and no disease progression on imaging at the current visit as per RECIST v1.1 (Sub study)
- No history of venous thrombo-embolic event, interstitial lung disease or any pre-existing condition that may impair participant’s respiratory function (per investigator assessment) (Sub study)
- Men or women ≥ 18 years of age
What rules you out
- Systemic antineoplastic therapy (except adjuvant therapies) received prior to AI and CDK4/6i
- Known leptomeningeal metastasis and/or brain metastasis
- Known contraindication to camizestrant and abemaciclib, per investigator assessment
- Prior exposure to camizestrant, other SERD or investigational endocrine therapy agents
- History of another malignancy, except (i) those treated with curative intent and with no known active disease ≥3 years; (ii) adequately treated non-melanoma cutaneous and in-situ cervix cancer
- Pregnant women or women who are breast-feeding or participants not willing to apply highly effective contraception as defined in the protocol
- Participants unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons
- Participation in another clinical study whose procedures interfere with those of the study (within 28 days prior to participant enrolment and for the duration of the study)
- Persons deprived of their liberty or under protective custody or guardianship
- History of bone marrow transplantation
- Patients relapsing while on or during the year after the discontinuation of adjuvant CDK4/6 inhibitor
- Participants with synchronous disease progression per local assessment (tumor imaging performed within 28 days prior to entry in Step #2 RECIST v1.1) (Related to step 2)
- Participants with a contraindication to abemaciclib, as assessed by the investigator
- Participants presenting any of the following cardiovascular conditions or findings a) unexplained syncope, symptomatic hypotension, or systolic blood pressure < 90 mmHg. b) second- and third-degree heart block, or clinically significant sinus pause or sinoatrial block (participants with pacemakers or medically controlled atrial fibrillation are not excluded). c) known left ventricular ejection fraction <50% with congestive heart failure NYHA Grade ≥ 2. d) experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, any other structural heart disease interventions (e.g., cardiac valve repair or replacement surgery or transcatheter valve intervention), severe aortic regurgitation (Grade 3 and 4), myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack. e) any clinically important abnormalities in rhythm, conduction or morphology that might impact resting ECG, such as third-degree heart block and any factors that increase the risk of QTc prolongation or the risk of arrhythmic events such as symptomatic heart failure, congenital long QT syndrome, immediate family history of long QT syndrome, unexplained sudden death at <40 years of age, hypertrophic cardiomyopathy and clinically significant stenotic valve disease, or clinically significant electrolyte abnormalities with potential QT-prolonging effect including hypokalaemia, hyperkalaemia, hypo- and hyper-magnesaemia, hypo- and hyper-calcaemia. Note: correction of electrolyte abnormalities to within normal ranges can be performed during screening). mean resting QTcF interval > 480 ms obtained from ECG performed at screening. g) resting heart rate < 55 beats per minute. Repeat measurements are permitted during the screening period. h) uncontrolled hypertension. Blood pressure systolic > 160 and diastolic > 90 mmHg. Hypertensive participants may be eligible, but blood pressure must be adequately controlled at baseline. Participants may be rescreened regarding blood pressure requirement.
- Participants treated within the last 2 weeks before randomization with medications that are sensitive substrates (e.g. omeprazole) or substrates with narrow therapeutic index of CYP2C9 and/or CYP2C19 (e.g. warfarin and phenytoin). Strong CYP3A4/5 inducers should be stopped at least 2 weeks before randomization (3 weeks for St John’s Wort).
- Participant who was treated within the timeframe indicated in the CSP with drugs that are known to prolong the QT interval.
- Participant taking medications known to prolong the QT interval and associated with a known risk of Torsades de Pointes
- Participant with a known active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), HBV (known positive HBsAg result), and HCV. 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 is negative for HCV RNA
- Participants known to be positive for HIV can be enrolled if they fulfil the criteria recommended by Food and Drug Administration (FDA) and ASCO guidelines (FDA Guidance, Uldrick et al 2017): CD4+ T-cell (CD4+) counts ≥350 cells/µL, AND No history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections within the past 12 months (prophylactic antimicrobials allowed if no DDI or overlapping toxicities), AND On established anti-retroviral therapy (ART) for at least 4 weeks and have an HIV viral load less than 400 copies/mL before enrolment. Effective ART is defined as a drug, dosage and schedule associated with reduction and control of the viral load
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.