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PHASE II STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CAMIZESTRANT PLUS RIBOCICLIB IN PATIENTS WITH HORMONE RECEPTOR-POSITIVE (HR+) BREAST CANCER (THE CADILLAC STUDY)
EU CTIS ID: 2024-520027-88-00
What this study is testing
To determine the median progression free survival (PFS), as assessed locally by the investigator in HR+/HER2- advanced breast cancer patients treated with camizestrant plus ribociclib as compared to PFS data obtained from historical control arm.
- Therapeutic exploratory (Phase II)
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
- Patient must be capable of understanding the purpose of the Study and have signed the written informed consent form (ICF) prior to beginning specific protocol procedures.
- Evidence of measurable disease as per RECIST v.1.1, or nonmeasurable, but evaluable, disease, including bone-only disease with at least one lytic or mixed lytic-blastic bone lesion.
- For patients receiving tamoxifen or toremifene, a washout period of 35 days (5 half-lives) prior to randomization is required
- Patients must agree to provide and have available a FFPE tissue biopsy sample taken at the time of presentation with recurrent or metastatic disease. If this is not available, archived primary breast cancer specimen may be submitted
- Adequate bone marrow and organ function: - Hematological (without platelet, red blood cell transfusion, and/or granulocyte colony-stimulating factor support within seven days before treatment initiation): White blood cell (WBC) count > 3.0 x 10^9 /L; absolute neutrophil count (ANC) ≥ 1.5 x 10^9 /L; platelet count ≥ 100.0 x10^9 and hemoglobin ≥ 9.0 g/dL. - Hepatic: Serum albumin ≥ 2.5 g/dL; total serum bilirubin < 1.5 x upper limit of normal (ULN) except for patients with Gilbert’s syndrome who may be included if the total serum bilirubin is ≤ 3 x ULN or direct bilirubin ≤ 1.5 x ULN; alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 3 x ULN in patients with liver and/or bone metastases); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 x ULN (≤ 3 x ULN in patients with liver metastases); international normalized ratio (INR) < 1.5. Prothrombin time (PT) or Prothrombin time-international normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT)/partial thromboplastin time (PTT) ≤ 1.5 × ULN, factor Xa inhibitors, or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator from product safety requirements (PSR). - Renal: Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min as calculated by Cockcroft-Gault equation.
- Patient must be available and willing to participate in the treatment and follow-up assessments as required.
You likely can't join if
- Formal contraindication to endocrine therapy defined as visceral crisis and/or rapidly or symptomatic progressive visceral disease.
- Major surgical procedure or significant traumatic injury within 14 days before Study enrollment or anticipation of need for major surgery within the course of the Study treatment.
- Cardiac symptoms, procedures, or test results as follows: Unexplained syncope (within the last six months prior to Study enrollment), or ongoing symptomatic hypotension, or ongoing asymptomatic hypotension with blood pressure systolic < 90 mmHg. Second- and third-degree heart block, or clinically significant sinus pause or sinoatrial block. Patients with pacemakers or medically controlled atrial fibrillation are not excluded. 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 < 40 years of age, hypertrophic cardiomyopathy and clinically significant stenotic valve disease. Known left ventricular ejection fraction (LVEF) <50% with heart failure NYHA Grade ≥ 2. Untreated electrolyte abnormalities with potential QT-prolonging effect including altered levels of serum/plasma potassium, magnesium, and calcium. Note: Correction of electrolyte abnormalities to within normal ranges can be performed during the screening period. Mean resting QTcF interval > 450 ms, obtained from triplicate-ECG performed at screening. Resting heart rate consistently 50-90 bpm. Repeat measurements are permitted during the screening period. Uncontrolled hypertension. Blood pressure systolic > 160 and diastolic > 90 mmHg despite optimal medical management. Note: Hypertensive patients may be eligible, but blood pressure must be adequately controlled at baseline. Experience of any of the following procedures or conditions in the preceding six 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 treatment), severe aortic regurgitation (Grades 3 and 4), myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack.
- Known abnormalities in coagulation such as bleeding diathesis, or any history of coagulopathy within six months before Study enrollment, including history of deep vein thrombosis or pulmonary embolism.
- Patients treated: Within 2 weeks prior to first dose: medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 (CYP) 3A4/5, sensitive CYP2B6 substrates, and drugs which are substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic range (e.g. warfarin/phenytoin) or who have not fully recovered from side effects of such treatment. With medications that are known to prolong the QT interval and have a known risk of Torsades de Pointes.
- Pregnant or lactating women or patients not willing to apply highly effective contraception as defined in the protocol.
See the full eligibility criteria
Who can join
- Patient must be capable of understanding the purpose of the Study and have signed the written informed consent form (ICF) prior to beginning specific protocol procedures.
- Evidence of measurable disease as per RECIST v.1.1, or nonmeasurable, but evaluable, disease, including bone-only disease with at least one lytic or mixed lytic-blastic bone lesion.
- For patients receiving tamoxifen or toremifene, a washout period of 35 days (5 half-lives) prior to randomization is required
- Patients must agree to provide and have available a FFPE tissue biopsy sample taken at the time of presentation with recurrent or metastatic disease. If this is not available, archived primary breast cancer specimen may be submitted
- Adequate bone marrow and organ function: - Hematological (without platelet, red blood cell transfusion, and/or granulocyte colony-stimulating factor support within seven days before treatment initiation): White blood cell (WBC) count > 3.0 x 10^9 /L; absolute neutrophil count (ANC) ≥ 1.5 x 10^9 /L; platelet count ≥ 100.0 x10^9 and hemoglobin ≥ 9.0 g/dL. - Hepatic: Serum albumin ≥ 2.5 g/dL; total serum bilirubin < 1.5 x upper limit of normal (ULN) except for patients with Gilbert’s syndrome who may be included if the total serum bilirubin is ≤ 3 x ULN or direct bilirubin ≤ 1.5 x ULN; alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 3 x ULN in patients with liver and/or bone metastases); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 x ULN (≤ 3 x ULN in patients with liver metastases); international normalized ratio (INR) < 1.5. Prothrombin time (PT) or Prothrombin time-international normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT)/partial thromboplastin time (PTT) ≤ 1.5 × ULN, factor Xa inhibitors, or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator from product safety requirements (PSR). - Renal: Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min as calculated by Cockcroft-Gault equation.
- Patient must be available and willing to participate in the treatment and follow-up assessments as required.
- Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 14 days before Study treatment initiation. In addition, they must agree to use one highly effective method of birth control from the time of screening until 4 weeks after the last dose of Study treatments. Female patients must refrain from egg cell donation and breastfeeding during this same period. Non-sterilized male partners of heterosexually active females of childbearing potential participants must use a male condom from the time of enrollment of their female partner, throughout their participation in the Study, and until 4 weeks after their female partner’s last dose of Study intervention.
- Male participants who are sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable highly effective method of contraception from the time of screening until 21 days after the last administration of the Study drug. Male participants must not donate or bank sperm during this same period. Female partners of childbearing potential of male participants must agree to use one highly effective method of contraception from the time of screening until 4 weeks after the last dose of Study treatments.
- ECOG performance status of 0-1.
- Minimum life expectancy of ≥ 6 months.
- Female or male patients ≥ 18 years of age at the time of signing ICF.
- Pre- or peri-menopausal women or men. are eligible if treated with a Luteinizing hormone-releasing hormone (LHRH) analogue. Treatment with a LHRH is recommended for at least 28 days prior to study treatment; if shorter, post-menopausal levels of serum estradiol/follicle-stimulating hormone [FSH] must be confirmed analytically prior to Study enrollment.
- Post-menopausal women, defined by any of the following criteria: o Cessation of menses for at least 12 consecutive months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. o Documented bilateral surgical oophorectomy.
- Documented histologically confirmed HR+ and human epidermal growth factor receptor 2 (HER2)-negative breast cancer according to the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as per local assessment on the most recent analyzed biopsy. Therefore, tumors must be: o HR+ defined as ≥ 10% of tumor cells stain positive for estrogen receptor (ER) on immunohistochemistry (IHC), and HER2- defined as 0 or 1+ intensity on IHC, or 2+ intensity on IHC and no evidence of amplification on in situ hybridization (ISH).
- Unresectable locally recurrent or metastatic disease confirmed by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
- Patients must have received at least five years of adjuvant endocrine therapy, including at least two years of an AI (capped to 30% patients with treatment-free interval [TFI] ≥ 12 months.
- Patients must have: - Radiological evidence of progression while on, or within 12 months of the end of (neo)adjuvant endocrine therapy (secondary endocrine resistance criteria), or - Radiological evidence of progression more than 12 months of the end of (neo)adjuvant endocrine therapy (endocrine sensitive criteria).
- Patients receiving a CDK4/6 inhibitor-based therapy in the (neo)adjuvant setting are eligible if disease progression is confirmed more than 12 months following CDK4/6 inhibitor treatment completion in this scenario.
What rules you out
- Formal contraindication to endocrine therapy defined as visceral crisis and/or rapidly or symptomatic progressive visceral disease.
- Major surgical procedure or significant traumatic injury within 14 days before Study enrollment or anticipation of need for major surgery within the course of the Study treatment.
- Cardiac symptoms, procedures, or test results as follows: Unexplained syncope (within the last six months prior to Study enrollment), or ongoing symptomatic hypotension, or ongoing asymptomatic hypotension with blood pressure systolic < 90 mmHg. Second- and third-degree heart block, or clinically significant sinus pause or sinoatrial block. Patients with pacemakers or medically controlled atrial fibrillation are not excluded. 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 < 40 years of age, hypertrophic cardiomyopathy and clinically significant stenotic valve disease. Known left ventricular ejection fraction (LVEF) <50% with heart failure NYHA Grade ≥ 2. Untreated electrolyte abnormalities with potential QT-prolonging effect including altered levels of serum/plasma potassium, magnesium, and calcium. Note: Correction of electrolyte abnormalities to within normal ranges can be performed during the screening period. Mean resting QTcF interval > 450 ms, obtained from triplicate-ECG performed at screening. Resting heart rate consistently 50-90 bpm. Repeat measurements are permitted during the screening period. Uncontrolled hypertension. Blood pressure systolic > 160 and diastolic > 90 mmHg despite optimal medical management. Note: Hypertensive patients may be eligible, but blood pressure must be adequately controlled at baseline. Experience of any of the following procedures or conditions in the preceding six 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 treatment), severe aortic regurgitation (Grades 3 and 4), myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack.
- Known abnormalities in coagulation such as bleeding diathesis, or any history of coagulopathy within six months before Study enrollment, including history of deep vein thrombosis or pulmonary embolism.
- Patients treated: Within 2 weeks prior to first dose: medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 (CYP) 3A4/5, sensitive CYP2B6 substrates, and drugs which are substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic range (e.g. warfarin/phenytoin) or who have not fully recovered from side effects of such treatment. With medications that are known to prolong the QT interval and have a known risk of Torsades de Pointes.
- Pregnant or lactating women or patients not willing to apply highly effective contraception as defined in the protocol.
- Current known infection with human immunodeficiency virus (HIV) detectable viral load, hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients 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. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
- Any other active uncontrolled infection at the time of screening.
- Known substance abuse or any other concurrent severe and/or uncontrolled psychiatric or medical condition that would, in the Investigator’s judgment, contraindicate patient participation.
- Current participation in another therapeutic clinical trial.
- Has previously been treated with any SERD, including camizestrant, experimental ETs or fulvestrant.
- Prior systemic therapy for advanced disease.
- Known active uncontrolled or symptomatic central nervous system (CNS) metastases and/or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases are eligible if they have been previously treated with local therapy, are clinically stable, and off anticonvulsants and steroids for at least 14 days before the first dose of Study treatment.
- History of another primary malignancy except for the following: a. Malignancy treated with curative intent with no known active disease ≥ 3 years before the first dose of Study treatment, and of very low potential risk for recurrence. b. Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease. c. Other exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin. Note: For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required.
- Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) or their incorporated substances. Note: Ribociclib is contraindicated for patients with hypersensitivity/allergy to peanut or soya.
- History of malabsorption syndrome or other condition that would interfere with enteral absorption (ongoing gastrointestinal obstruction/motility disorder, malabsorption syndrome, or prior gastric bypass) or results in the inability or unwillingness to swallow pills.
- Palliative radiotherapy with a limited field of radiation within two weeks or with wide field of radiation or radiation to more than 30% of the bone marrow within four weeks prior to Study enrollment.
The study team makes the final eligibility decision.
Where it's taking place
- China
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.
Where is this trial taking place?
Study sites include China. Enter your location above to see the nearest site and check your eligibility.
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.