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

NCT ID: NCT06190899

Last Updated: 2025-03-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-01

Study Completion Date

2027-11-30

Brief Summary

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This is a Phase 1/2, open-label, randomized, dose finding and dose expansion study to evaluate the safety, preliminary efficacy, and PK of gedatolisib in combination with darolutamide in subjects with mCRPC.

Detailed Description

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This is a Phase 1/2, open-label, randomized, dose finding and dose expansion study to evaluate the safety, preliminary efficacy, and pharmacokinetics of gedatolisib, a pan-PI3K/mTOR inhibitor, in combination with darolutamide, a next-generation androgen receptor inhibitor, in patients with metastatic castration-resistant prostate cancer following progression on a next-generation androgen receptor inhibitor. The aim of the Phase 1 portion of the study is to evaluate dose limiting toxicities and to determine the recommended Phase 2 dose. The aim of the Phase 2 portion of the study is to further assess the safety and preliminary efficacy of the drug combination.

Conditions

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mCRPC (Metastatic Castration-resistant Prostate Cancer) Genital Diseases, Male Urogenital Diseases, Male Prostatic Disease Prostatic Neoplasms, Castration-Resistant Prostate Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a Phase 1/2, open-label, randomized, dose finding and dose expansion study to evaluate the safety, preliminary efficacy, and PK of gedatolisib in combination with darolutamide in subjects with mCRPC. The study is comprised of two phases:

* Phase 1 Dose Finding (2 Parts)

o Part 1: DLT evaluation and determination of tolerated doses
* Part 2: Determination of RP2D
* Phase 2 Dose Expansion
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1 Arm 1

Arm 1 - 120 mg of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)

Group Type EXPERIMENTAL

Gedatolisib

Intervention Type DRUG

Gedatolisib is a potent reversible inhibitor that selectively targets all Class I PI3K isoforms and mTOR.

Darolutamide

Intervention Type DRUG

Darolutamide is a novel androgen receptor inhibitor that has been studied and received approval for treatment of patients with nonmetastatic CRPC and in metastatic hormone-sensitive prostate cancer.

Phase 1 Arm 2

Arm 2 - 180 mg of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)

Group Type EXPERIMENTAL

Gedatolisib

Intervention Type DRUG

Gedatolisib is a potent reversible inhibitor that selectively targets all Class I PI3K isoforms and mTOR.

Darolutamide

Intervention Type DRUG

Darolutamide is a novel androgen receptor inhibitor that has been studied and received approval for treatment of patients with nonmetastatic CRPC and in metastatic hormone-sensitive prostate cancer.

Phase 2

The recommended Phase 2 dose (RP2D) of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)

Group Type EXPERIMENTAL

Gedatolisib

Intervention Type DRUG

Gedatolisib is a potent reversible inhibitor that selectively targets all Class I PI3K isoforms and mTOR.

Darolutamide

Intervention Type DRUG

Darolutamide is a novel androgen receptor inhibitor that has been studied and received approval for treatment of patients with nonmetastatic CRPC and in metastatic hormone-sensitive prostate cancer.

Interventions

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Gedatolisib

Gedatolisib is a potent reversible inhibitor that selectively targets all Class I PI3K isoforms and mTOR.

Intervention Type DRUG

Darolutamide

Darolutamide is a novel androgen receptor inhibitor that has been studied and received approval for treatment of patients with nonmetastatic CRPC and in metastatic hormone-sensitive prostate cancer.

Intervention Type DRUG

Other Intervention Names

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NUBEQA

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Celcuity Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nadene Zack, MS

Role: STUDY_DIRECTOR

Celcuity Inc

Locations

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Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status RECRUITING

Centre Jean Perrin

Clermont-Ferrand, , France

Site Status NOT_YET_RECRUITING

Institut Paoli-Calmettes

Marseille, , France

Site Status NOT_YET_RECRUITING

Centre Antoine Lacassagne

Nice, , France

Site Status NOT_YET_RECRUITING

Institut Gustave Roussy

Villejuif, , France

Site Status NOT_YET_RECRUITING

Hospital Clinic Barcelona

Barcelona, , Spain

Site Status RECRUITING

Institut Catala d'Oncologia

Barcelona, , Spain

Site Status RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status NOT_YET_RECRUITING

Hospital 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Instituto Valenciano de Oncología

Valencia, , Spain

Site Status NOT_YET_RECRUITING

Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospita

Cambridge, , United Kingdom

Site Status NOT_YET_RECRUITING

University Hospital Southampton NHS Foundation Trust - Southampton General Hospital

Southampton, , United Kingdom

Site Status NOT_YET_RECRUITING

Royal Marsden NHS Foundation Trust

Sutton, , United Kingdom

Site Status RECRUITING

Countries

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United States France Spain United Kingdom

Central Contacts

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Genelle Brower, RN

Role: CONTACT

844-310-3900

Other Identifiers

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CELC-G-201

Identifier Type: -

Identifier Source: org_study_id

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