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

Prostate Cancer Clinical Trial

Official title:

A Phase 1/2, Open-Label, Randomized, Dose Finding and Dose Expansion Study of Gedatolisib in Combination With Darolutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06190899
• Other study ID #: CELC-G-201
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 1, 2024
• Est. completion date: November 2027

Study information

• Verified date: January 2024
• Source: Celcuity Inc
• Contact: Genelle Brower, RN
• Phone: 844-310-3900
• Email: gbrower[@]celcuity.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: November 2027
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Genital Diseases, Male
• Male Urogenital Diseases
• Prostate Cancer
• Prostatic Disease
• Prostatic Diseases
• Prostatic Neoplasms
• Prostatic Neoplasms, Castration-Resistant
• Urogenital Diseases

Intervention

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

Locations

Country	Name	City	State
France	Centre Jean Perrin	Clermont-Ferrand
France	Institut Paoli-Calmettes	Marseille
France	Centre Antoine Lacassagne	Nice
France	Institut Gustave Roussy	Villejuif
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Institut Catala d'Oncologia	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Instituto Valenciano de Oncología	Valencia
United Kingdom	Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospita	Cambridge
United Kingdom	University Hospital Southampton NHS Foundation Trust - Southampton General Hospital	Southampton
United Kingdom	Royal Marsden NHS Foundation Trust	Sutton
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Celcuity Inc

Countries where clinical trial is conducted

United States,  France,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Assessment of the safety and tolerability of gedatolisib in combination with darolutamide in metastatic castration-resistant prostate cancer (mCRPC)	Type, incidence, severity (as graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v5.0), seriousness, and relationship to study medications of adverse events (AEs) and any laboratory abnormalities	Cycle 1, Day 1 to end of safety follow up (each cycle is 28 days and safety follow up will continue until 30 days after last dose of study medication)
Primary	Phase 1: Identification of the recommended Phase 2 dose (RP2D) of gedatolisib in combination with darolutamide in mCRPC	Incidence of dose-limiting toxicities (DLTs) and AEs graded according to NCI CTCAE v5.0	Through Phase I completion, an average of 1 year.
Primary	Phase 2: Assessment of the antitumor activity of gedatolisib in combination with darolutamide in each arm as demonstrated by radiographic progression-free survival (rPFS) by arm	Radiographic progression-free survival rate at 6 months as measured by the Kaplan-Meier (K-M) method and assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 with modifications as specified in Prostate Cancer Working Group 3 (PCWG3) criteria	6 months
Secondary	Assessment of the preliminary efficacy of gedatolisib in combination with darolutamide by arm	Radiographic progression-free survival rates at 9 and 12 months and overall rPFS Overall Survival (OS) rate at 18 and 24 months	9 and 12 months post Cycle 1 Day 1 (each cycle is 28 days); 18 and 24 months post Cycle 1 Day 1 (each cycle is 28 days)