CAPTOR-BC: COMPREHENSIVE ANALYSIS OF SPATIAL, TEMPORAL AND MOLECULAR PATTERNS OF RIBOCICLIB EFFICACY AND RESISTANCE IN ADVANCED BREAST CANCER PATIENTS
- Trial ID
- 2022-500764-35-00
- Protocol
- IFG-01-2022
Trial statistics
Objectives
The primary objective of the CAPTOR-BC trial is to estimate the **survival rates** of progression-free survival (PFS) and overall survival (OS) at 12 months in patients with advanced HER2-negative, hormone receptor-positive breast cancer in the first-line therapeutic setting. This objective is clinically relevant as it aims to provide insights into the efficacy of ribociclib in prolonging survival without disease progression and overall survival, which are critical endpoints in the management of advanced breast cancer.
Secondary objectives include:
- Progression-free survival rates at 24 and 36 months
- Overall survival rates at 24 and 36 months
- Median progression-free survival, if achieved at study end
- Median overall survival, if achieved at study end
- Health-related quality of life assessed by FACT-G/FACT-B
- Side effects assessed by NCI-CTCAE v.5.0
These secondary objectives aim to provide a comprehensive evaluation of the long-term efficacy, safety, and impact on quality of life of the treatment regimen, which are essential for optimizing therapeutic strategies in this patient population.
Participants
The clinical trial involves **female** participants aged **18 years and older** diagnosed with advanced **HER2-negative, hormone receptor positive (HER2neg/HR+) breast cancer**. The study population is specifically selected to include individuals who are indicated for treatment with ribociclib in combination with endocrine therapy in the locally advanced or first-line metastatic therapy setting. Participants must have a confirmed diagnosis of HER2-negative breast cancer, as determined by local laboratory tests, and must exhibit adequate organ function for treatment. The trial does not include male subjects, and the sponsor has not provided the total number of participants. Participants are required to comply with scheduled visits and trial procedures, and women of childbearing potential must adhere to specific contraceptive measures. The trial population is considered vulnerable, and all participants must provide written informed consent prior to the commencement of trial-specific procedures.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and resistance patterns of **ribociclib** in patients with advanced HER2-negative, hormone receptor-positive breast cancer. This is a Phase IV, randomized, double-blind, controlled trial. The trial aims to estimate progression-free survival (PFS) and overall survival (OS) at 12 months as co-primary objectives. The trial is expected to run from October 2022 to October 2027, with a maximum treatment period of 48 months for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as HER2-negative status, hormone receptor positivity, and adequate organ function. Following the screening, eligible participants will be randomized to receive **ribociclib** in combination with endocrine therapy, including **letrozole**, **exemestane**, **anastrozole**, or **fulvestrant**. The treatment will be administered orally, except for **fulvestrant**, which will be given via intramuscular injection. The maximum daily doses are 600 mg for **ribociclib**, 2.5 mg for **letrozole**, 25 mg for **exemestane**, 1 mg for **anastrozole**, and 500 mg for **fulvestrant**.
Participants will attend regular follow-up visits to monitor treatment efficacy and safety, including assessments of progression-free survival, overall survival, and health-related quality of life. The occurrence of side effects will also be documented. The end-of-study visit will conclude the participant's involvement, unless early termination is warranted due to adverse events, disease progression, or withdrawal of consent. The expected length of participant involvement is up to 48 months, contingent upon individual response and tolerance to the treatment regimen.
Treatment
The clinical trial involves the administration of several **antineoplastic** agents, each with specific roles and administration protocols. **Letrozole** is utilized in this study as an auxiliary treatment. It is administered orally in a pharmaceutical form identified as PHF00082MIG. The maximum daily dose is 2.5 mg, with a total dose not exceeding 2.5 mg per day. The treatment period is capped at 48 months. Letrozole functions as an enzyme inhibitor, contributing to the antineoplastic effects required in the study.
**Exemestane** is another auxiliary treatment in the trial, administered orally in the pharmaceutical form PHF00009MIG. The maximum daily dose is set at 25 mg, with the same amount as the total daily dose. The treatment duration is also limited to 48 months. Exemestane acts as an aromatase inhibitor, playing a crucial role in the antineoplastic regimen.
**Anastrozole** is included as an auxiliary treatment, administered orally in the same pharmaceutical form as Exemestane, PHF00009MIG. The maximum daily and total dose is 1 mg, with a treatment period of up to 48 months. Anastrozole serves as an enzyme inhibitor, contributing to the antineoplastic strategy of the trial.
**Ribociclib** is the primary test treatment in this clinical trial. It is administered orally in the form of a film-coated tablet. The maximum daily and total dose is 600 mg, with a treatment period extending up to 48 months. Ribociclib is a key component of the antineoplastic treatment plan, focusing on its efficacy and resistance patterns in advanced breast cancer patients.
**Fulvestrant** is used as an auxiliary treatment, administered via intramuscular injection in the pharmaceutical form PHF00231MIG. The maximum daily dose is 17 mg, with a total dose of 500 mg. The treatment period is set at 48 months. Fulvestrant functions as an endocrine therapy and antiestrogen, supporting the antineoplastic objectives of the trial.
Efficacy
Efficacy in the clinical trial titled "CAPTOR-BC: COMPREHENSIVE ANALYSIS OF SPATIAL, TEMPORAL AND MOLECULAR PATTERNS OF RIBOCICLIB EFFICACY AND RESISTANCE IN ADVANCED BREAST CANCER PATIENTS" will be assessed using the co-primary endpoints of **progression-free survival** (PFS) and **overall survival** (OS) at 12 months. These endpoints are critical in evaluating the effectiveness of the treatment regimen involving **ribociclib** in combination with endocrine therapy for patients with advanced breast cancer.
Secondary endpoints include health-related quality of life measured by FACT-G/FACT-B and the occurrence of side effects. The trial will collect data on these parameters at specified intervals throughout the study duration, which is estimated to conclude by October 2027. The assessment of these endpoints will involve validated scales and laboratory tests to ensure accurate and reliable data collection. The trial aims to provide comprehensive insights into the efficacy and resistance patterns of ribociclib in the specified patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Indication for treatment with ribociclib in combination with endocrine therapy in the locally advanced or 1st line metastatic therapy setting according to SmPC. (Previous treatment with CDK4/6 inhibitors is allowed in the adjuvant setting)
- Written informed consent prior to beginning of trial specific procedures
- Subject must be female and aged ≥ 18 years on the day of signing informed consent
- Locally advanced or metastatic breast cancer not amenable to curative treatment
- Patient has HER2-negative breast cancer confirmed by local laboratory defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required to confirm the HER2-negative status (based on the most recently analyzed tissue sample tested by a local laboratory
- Histologically confirmed ER positive and/ or PgR positive breast cancer determined by core biopsy according to local in-house standard
- QTcF interval < 450 ms
- Adequate organ function amenable for treatment with ribociclib as assessed by local laboratory
- Women of childbearing potential must have a negative urine or serum pregnancy test within 72 h prior to study entry and be willing to use highly effective method of contraception for course of the trial through 21 days after the last dose of trial treatment
- Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures
Exclusion Criteria
- Concurrent participation in a study with an investigational agent/device or within 14 days of study entry or 5 half-lives of the respective investigational agent/device, whichever is longer
- Patients who are not treated for advanced HRpos/HER2neg breast cancer in the first line therapy setting
- Patients not eligible for treatment with ribociclib according to SmPC or investigator’s discretion
- Patients who are pregnant or lactating
- Patients with existing or patients who are at significant risk of developing QTc prolongation. This includes patients with long QT syndrome, uncontrolled or significant cardiac disease, including recent myocardial infarction, congestive heart failure, unstable angina and bradyarrhythmia, electrolyte abnormalities
- Patients with known hypersensitivity to the active substance of ribociclib, soya, peanut or any other of the excipients of ribociclib
- Patients with active systemic infections (for example, bacterial infection requiring intravenous antibiotics at time of initiating study treatment, fungal infection, or detectable viral infection requiring systemic therapy) or viral load (such as known human immunodeficiency virus positivity or with known active hepatitis B or C, for example, hepatitis B surface antigen positive)
- Patients with serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (such as severe renal impairment, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis or a preexisting chronic condition resulting in clinically significant diarrhea)
- Patients who do not agree to collection of biospecimens samples (blood, stool, tissue)
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 01 Oct 2022 | 2000 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ANASTROZOLE | Other | PHF00009MIG | ORAL | 1 | 48 | SCP140009 |
FULVESTRANT | Other | PHF00231MIG | INTRAMUSCULAR INJECTION | 17 | 48 | SCP40295237 |
LETROZOLE | Other | PHF00082MIG | ORAL | 2.5 | 48 | SCP236273 |
EXEMESTANE | Other | PHF00009MIG | ORAL | 25 | 48 | SCP139728 |
RIBOCICLIB | Test | — | ORAL USE | 600 | 48 | SUB180246 |