Combination of Gedatolisib and Darolutamide for Advanced Prostate Cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 1/2 clinical trial evaluates the safety and preliminary efficacy of gedatolisib, a pan-PI3K/mTOR inhibitor, in combination with darolutamide, an androgen receptor inhibitor, in adult males with metastatic castration-resistant prostate cancer (mCRPC). The study is designed as an open-label, randomized trial that includes a dose-finding phase to identify the optimal dosage and a subsequent phase to further assess the treatment's effectiveness. Patients will be monitored for dose-limiting toxicities and overall response to the treatment regimen.

Why it matters

Who can join: the full rules

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

Where it's running

• Barbara Ann Karmanos Cancer Institute
  Detroit, Michigan, United States Recruiting
• Hospital Clinic Barcelona
  Barcelona, Spain Recruiting
• Institut Catala d'Oncologia
  Barcelona, Spain Recruiting
• Hospital 12 de Octubre
  Madrid, Spain Recruiting
• Royal Marsden NHS Foundation Trust
  Sutton, United Kingdom Recruiting
• Centre Jean Perrin
  Clermont-Ferrand, France Not yet recruiting

Study contacts

• Study coordinator: Genelle Brower, RN
• Email: gbrower@celcuity.com
• Phone: 844-310-3900

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.