Phase II Evaluation of Pembrolizumab and Carboplatin in BRCA-Mutated Metastatic Breast Cancer
- Trial ID
- 2024-515686-34-00
- Protocol
- PEMBRACA
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this phase II study is to evaluate the **Objective Response Rate (ORR)**, which includes both complete and partial responses, in patients with **BRCA-related metastatic breast cancer**. This evaluation will be conducted according to the RECIST v1.1 criteria. The ORR is a critical measure of the efficacy of the treatment regimen, as it provides insight into the proportion of patients who experience a significant reduction in tumor size, which is a key indicator of treatment success in oncology.
Secondary objectives include:
- Time to Progression (TTP): Calculated as the time from enrollment to disease progression, providing a measure of how long the treatment can delay disease advancement.
- Duration of Response (DOR): Measured from the first recorded ORR to the date of documented progression, indicating the sustainability of the treatment response.
- Disease Control Rate (DCR): Evaluated as the percentage of patients achieving ORR and stable disease, offering a broader view of treatment impact beyond ORR.
- Overall Survival (OS): Considered as the interval from enrollment to death or the last known date the patient was alive, serving as a comprehensive endpoint for treatment efficacy.
- Safety: Assessed by the worst toxicity grade reported during the treatment period, ensuring the treatment's risk profile is acceptable.
Participants
The clinical trial involves participants diagnosed with **BRCA-related metastatic breast cancer**. The study population includes both male and female subjects, with an age range of 18 years and older. Participants are required to have a confirmed diagnosis of metastatic breast cancer with documented mutations in the BRCA1 or BRCA2 genes. The trial does not focus on a vulnerable population, and participants must have a performance status of 0 or 1 on the ECOG Performance Scale, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The sponsor has not provided the total number of participants. Participants must have undergone prior chemotherapy with anthracyclines and taxanes, and no more than one line of chemotherapy for advanced disease. The trial population was selected based on specific inclusion criteria, including the presence of at least one measurable lesion and a life expectancy of greater than three months. Adequate organ function is also a requirement, as defined by the trial's screening labs. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **pembrolizumab** in combination with carboplatin for patients with BRCA-related metastatic breast cancer. This is a Phase II, randomized, double-blind, controlled study. The trial aims to assess the objective response rate (ORR), which includes complete and partial responses, according to RECIST v1.1 criteria. The estimated duration of the trial is from July 31, 2018, to December 31, 2025, with participant involvement expected to last up to 60 weeks.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, confirmed diagnosis of metastatic breast cancer, documented BRCA1 or BRCA2 mutations, and adequate organ function. Following the screening, eligible participants will be randomized to receive the investigational treatment. Study visits will include regular follow-up assessments to monitor the safety and efficacy of the treatment, as well as to collect data on the primary and secondary endpoints. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination.
Participants may be withdrawn from the study if they experience unacceptable toxicity, disease progression, or if they withdraw consent. Additionally, any significant protocol deviations or safety concerns may lead to early termination from the study. The trial is conducted under strict adherence to ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.
Treatment
The clinical trial involves the administration of **Pembrolizumab**, a monoclonal antibody used in the treatment of various cancers. Pembrolizumab is provided in two pharmaceutical forms for this study. The first form is a concentrate for solution for infusion, marketed under the name **KEYTRUDA**. This formulation contains 25 mg/mL of Pembrolizumab and is administered via **intravenous infusion**. The maximum daily dose for this formulation is 200 mg, with a total treatment period extending up to 60 days. The administration schedule is designed to ensure optimal therapeutic efficacy while monitoring for any adverse effects. Compliance with the dosing regimen is monitored through regular assessments and documentation of infusion sessions.
The second form of Pembrolizumab used in the trial is a pharmaceutical form identified as PHF00230MIG. This formulation is also administered through **IV infusion**. The maximum daily dose for this form is 25 mg/mL, with a total treatment period of up to 5 days. The dosing schedule is carefully structured to align with the study's objectives, and participant adherence is closely monitored to ensure consistency and reliability of the trial results. Both formulations of Pembrolizumab are utilized in conjunction with standard-of-care therapies, and no placebo or comparator treatments are employed in this study. The trial aims to evaluate the overall response rate (ORR) in patients with BRCA-related metastatic breast cancer, following the RECIST v1.1 criteria.
Efficacy
Efficacy in the clinical trial will be assessed by evaluating the **objective response rate (ORR)**, which includes both complete and partial responses. The assessment will be conducted according to the RECIST v1.1 criteria, a standardized set of guidelines for evaluating changes in tumor size and response to treatment. The primary endpoint of the trial is the objective response rate, which will be measured to determine the effectiveness of the treatment regimen involving **Pembrolizumab** plus Carboplatin in patients with BRCA-related metastatic breast cancer. The trial will involve regular monitoring and evaluation of tumor response at specified intervals, ensuring that the data collected is consistent and reliable for analysis. The use of RECIST v1.1 criteria provides a validated and widely accepted method for assessing tumor response, facilitating the comparison of results across different studies and enhancing the robustness of the efficacy evaluation.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Be willing and able to provide written informed consent/assent for the trial. 2. Be >=18 years of age on day of signing informed consent. 3. Patients must have metastatic confirmed breast cancer 4. Disease progression by radiological techniques within 12 months prior to signing informed consent 5. Documented mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious (unknown significance variants) 6. Presence of at least 1 measurable lesion based on RECIST v1.1. 7. Prior chemotherapy with anthracyclines and taxanes has to be administered. 8. No more than one line of chemotherapy for advanced disease has to be administered 9. In case of luminal tumors hormonal treatments for advanced disease can be administered before 10. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen 11. Have a performance status of 0 or 1 on the ECOG Performance Scale. 12. Life expectancy of greater than 3 months 13. Demonstrate adequate organ function as defined. All screening labs should be performed within 10 days of treatment initiation.
Exclusion Criteria
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 2. Has a benign variant of BRCA1/2 genes 3. Has received more than one line of chemotherapy for advanced disease 4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. 5. Has a known history of active TB (Bacillus Tuberculosis) 6. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients. 7. Has had an allogenic tissue/solid organ transplant 8. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 9. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and may qualify for the study. - Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 10. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 11. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 12. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. 13. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. 14. Has an active infection requiring systemic therapy. 15. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 16. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 17. Has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Is exclude also women pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the prescreening or screening visit through 120 days after the last dose of trial treatment.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Recruiting | 31 Jul 2018 | 53 |
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 |
|---|---|---|---|---|---|---|
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 200 | 60 | PRD4323105 |
PEMBROLIZUMAB | Test | PHF00230MIG | IV INFUSION | 25 | 5 | SCP6094344 |