Gedatolisib in Combination With Darolutamide in Metastatic Castration-Resistant Prostate Cancer

Launched by CELCUITY INC · Jan 2, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for men with metastatic castration-resistant prostate cancer (mCRPC). The researchers want to find out if combining two drugs, gedatolisib and darolutamide, is safe and effective. This trial is currently looking for adult men aged 18 and older who have been diagnosed with prostate cancer that has spread and is resistant to standard hormone treatments. To be eligible, participants must show signs of disease progression, which can be measured through specific medical tests like blood tests or imaging scans.

If you decide to participate, you will receive either gedatolisib in combination with darolutamide or just darolutamide alone. The trial aims to assess how well this combination works and monitor any side effects. Participants can expect regular check-ups and tests to track their health throughout the study. It's important to know that you cannot join if you have certain other health conditions or have received specific previous treatments. This trial is a step toward finding better options for managing mCRPC, and your involvement could contribute to important research that may help others in the future.

Gender

MALE

Eligibility criteria

• • Inclusion Criteria
• • 1. Adult males ≥18 years of age
• • 2. Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate without a small cell component and with \<10% neuroendocrine type cells
• • 3. Subjects must have metastatic castration-resistant prostate cancer (mCRPC; i.e., developed progression of metastases following surgical castration or during medical androgen ablation therapy)
• • 4. Metastatic disease identified by conventional imaging: computed tomography (CT), magnetic resonance imaging (MRI), or technetium 99m-methyl diphosphonate (99mTc-MDP) bone scintigraphy. Measurable and non-measurable disease are allowed, but metastases visible only on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) will not be allowed for eligibility purposes.
• 5. Progressive mCRPC based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 with modifications as specified in Prostate Cancer Working Group 3 (PCWG3) criteria as defined by at least one of the following criteria:
• • 5.1. Prostate-specific antigen (PSA) progression defined as a minimum of 2 rising PSA levels with a minimum of a 1-week interval between each determination. A minimum PSA of 1.0 ng/mL is required for study entry.
• • 5.2. Soft-tissue progression defined as an increase ≥20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions. 5.3. Progression of bone disease (measurable disease) or 2 or more new bone lesions by bone scan.
• • 6. Continued primary androgen deprivation with luteinizing hormone-releasing hormone (LHRH) analog (agonist or antagonist) if the subject has not undergone bilateral orchiectomy
• • 7. Eastern Cooperative Oncology Group (ECOG) performance status score ≤1
• • 8. Progression during treatment with one next-generation androgen receptor signaling inhibitor for metastatic disease (e.g., abiraterone, enzalutamide, apalutamide, darolutamide)
• • 9. Completion of prior treatment with an androgen receptor inhibitor (ARi) ≥4 weeks before the first dose of the study drug
• • 10. At least 2 weeks beyond treatment with a targeted therapy or major surgery and at least 3 weeks beyond any other systemic anticancer therapy and/or radiation therapy, and resolution of all toxicities related to prior therapies or surgical procedures to baseline (except alopecia, Grade 1 peripheral neuropathy)
• • 11. Adequate bone marrow, hepatic, renal and coagulation function
• • Exclusion Criteria
• • 1. History of malignancies other than adequately treated non-melanoma skin cancer or other solid tumors curatively treated with no evidence of disease for ≥3 years
• • 2. Adenocarcinoma of the prostate with a small cell component, and with ≥10% neuroendocrine type cells
• • 3. Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor, a protein kinase B (AKT) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor
• • 4. Prior treatment with chemotherapy or radiopharmaceutical therapy for mCRPC (except prior chemotherapy plus ADT for castration-sensitive disease, including docetaxel plus darolutamide).
• • 5. Subjects with uncontrolled type 1 or type 2 diabetes
• • 9. Known and untreated, or active, brain or leptomeningeal metastases. Subjects with previously treated central nervous system (CNS) metastases may be enrolled in the study if they meet the following criteria: do not require supportive therapy with steroids; do not have seizures and do not exhibit uncontrolled neurological symptoms; stable disease confirmed by radiographic assessment within at least 4 weeks prior to randomization 10. History of clinically significant cardiovascular abnormalities 11. Gastrointestinal tract disease resulting in an inability to absorb oral medication as well as history of inflammatory bowel disease 12. Unable to swallow oral medication tablets/capsules