GEDATOLISIB for Metastatic castration-resistant prostate cancer

Inclusion criteria

• {"criterion_text":"- 1.\tAdult males ≥18 years of age\n- 10.\tCompletion of prior treatment with an androgen receptor inhibitor (ARi) ≥4 weeks before first dose of study drug or ≥2 weeks if the therminal ARi half-life is <24 hours\n- 11.\tAt 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)\n- 12.\tAdequate bone marrow, hepatic, renal and coagulation function\n- 13.\tMust be willing and able to comply with protocol-specified schedules of assessments, treatment plans, laboratory tests, and other study procedures\n- 14.\tMust agree to follow the contraception requirements for the duration of the active treatment period and for at least 12 weeks after the last dose of study treatment\n- 15.\tAbility to understand the investigational nature of the study and sign the informed consent form\n- 2.\tHistologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate without a small cell component and with <10% neuroendocrine type cells\n- 3.\tSubjects must have metastatic castration-resistant prostate cancer (mCRPC; i.e., developed progression of metastases following surgical castration or during medical androgen ablation therapy)\n- 4.\tMetastatic 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.\n- 5.\tProgressive 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: a.\tProstate-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. b.\tSoft-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. c.\tProgression of bone disease (measurable disease) or 2 or more new bone lesions by bone scan.\n- 6.\tContinued primary androgen deprivation with luteinizing hormone-releasing hormone (LHRH) analog (agonist or antagonist) if subject has not undergone bilateral orchiectomy\n- 7.\tEastern Cooperative Oncology Group (ECOG) performance status score ≤1\n- 8.\tLife expectancy of at least 3 months\n- 9.\tSubjects must meet the following prior therapy criteria: a. Progression on or after treatment with one next generation androgen receptor signaling inhibitor for metastatic disease (e.g., abiraterone, enzalutamide, apalutamide, darolutamide) b. Subjects with known BRCA mutation positive status should have recevied PARP inhibitor therapy before trial entry (unless contraindicated or unavailable)"}

Exclusion criteria

• {"criterion_text":"- 1.\tHistory of malignancies other than adequately treated non-melanoma skin cancer or other solid tumors curatively treated with no evidence of disease for ≥3 years\n- 10. History of clinically significant cardiovascular abnormalities such as: a. Congestive heart failure (New York Heart Association [NYHA] classification ≥II (NYHA 1994) within 6 months of study entry. b. Myocardial infarction within 12 months of study entry. c. History of any uncontrolled (or untreated) clinically significant cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle branch block, high grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block), supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months. d. Uncontrolled hypertension defined by systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) ≥100 mmHg, with or without antihypertensive medication (initiation or adjustment of antihypertensive medication[s] is allowed prior to screening). e. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: i. Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia or history of clinically significant/symptomatic bradycardia. ii. On screening, inability to determine the corrected QT interval using Fridericia’s formula (QTcF) on the electrocardiogram (ECG; i.e., unreadable or not interpretable) or QTcF >470 msec (determined by mean of triplicate ECGs at screening).\n- 11. Gastrointestinal tract disease resulting in an inability to absorb oral medication as well as history of inflammatory bowel disease.\n- 12. Unable to swallow oral medication tablets/capsules.\n- 13. On more than 10 mg of prednisolone/prednisone (or equivalent) per day.\n- 14. Known hypersensitivity to the study drugs or their components.\n- 15. History of drug-induced pneumonitis or interstitial lung disease.\n- 16. Current uncontrolled medical conditions that, in the opinion of the Investigator, could limit a subject’s ability to undertake study therapy or comply with study requirements.\n- 17. Current participation in another interventional clinical trial. a. Subjects must agree not to participate in another clinical trial (other than observational trials) at any time during participation in CELC-G-201.\n- 18. Subjects with rapidly progressive disease who are eligible for standard chemotherapy are excluded from enrollment.\n- 2. Adenocarcinoma of the prostate with a small cell component, or with ≥10% neuroendocrine type cells.\n- 3. Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor, a protein kinase B (AKT) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor.\n- 4. Prior treatment with chemotherapy or radiopharmaceutical therapy for mCRPC. a. Prior docetaxel in combination with ADT and ARi (darolutamide or abiraterone) for castration sensitive prostate cancer (CSPC) is allowed.\n- 5. Subjects with uncontrolled type 1 or type 2 diabetes.\n- 6. Known active human immunodeficiency virus (HIV) infection. a. Subjects with well-controlled HIV infection may be allowed if CD4+ T-cell (CD4+) counts >350 cells/μL. b. Subjects without a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections may be eligible for enrollment.\n- 7. Known history/positive serology for acute or chronic hepatitis B virus (HBV) infection (unless immune due to vaccination or resolved natural infection): a. Positive test for antibodies to hepatitis B core antigens (anti-HBc), and negative test for antibodies to hepatitis B surface antigens (anti-HBs). b. Positive for hepatitis B surface antigen (HBsAg).\n- 8. Known seropositive for, or active infection with, hepatitis C virus (HCV). a. Subjects with positive hepatitis C virus antibodies are eligible with negative polymerase chain reaction (PCR) test for HCV.\n- 9. Known and untreated, or active, brain or leptomeningeal metastases. a. 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."}

Primary endpoints

• {"endpoint_text":"- Phase 1: 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","definition_or_measurement_approach":"AEs and laboratory abnormalities graded by NCI CTCAE v5.0; assessment of type, incidence, severity, seriousness and relationship to study medications."}
• {"endpoint_text":"- Phase 1: BOIN utility score, which includes pre-defined toxicity criteria and 6-month radiographic progression-free survival (rPFS) binary outcomes","definition_or_measurement_approach":"BOIN utility score combining pre-defined toxicity criteria and binary 6-month rPFS outcomes."}
• {"endpoint_text":"- Phase 1: Incidence of dose-limiting toxicities (DLTs) and AEs graded according to NCI CTCAE v5.0","definition_or_measurement_approach":"DLTs and AEs graded per NCI CTCAE v5.0; incidence measured during DLT assessment window as defined in protocol."}
• {"endpoint_text":"- Phase 2: rPFS 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","definition_or_measurement_approach":"Radiographic progression-free survival (rPFS) evaluated using RECIST v1.1 with PCWG3 modifications; rPFS rate estimated at 6 months using Kaplan–Meier method."}

Secondary endpoints

• {"endpoint_text":"- Phase 1: Gedatolisib maximum observed concentration (Cmax), area under the plasma concentration-time curve from time 0 to 24 hours (AUC0-24; Cycle 2 only), and area under the plasma concentration-time curve from 0 to last measurable concentration (AUC0-t)","definition_or_measurement_approach":"PK parameters: Cmax, AUC0-24 (Cycle 2 only), AUC0-t measured from plasma concentration-time data."}
• {"endpoint_text":"- Phase 2: rPFS rates at 9 and 12 months and overall rPFS","definition_or_measurement_approach":"rPFS rates at 9 and 12 months and overall rPFS estimated using Kaplan–Meier analysis per RECIST v1.1 with PCWG3 modifications."}
• {"endpoint_text":"- Phase 2: Overall response rate (ORR): percentage of subjects who achieved an objective response (OR) based on RECIST v1.1 with modifications as specified in PCWG3 criteria for all efficacy endpoints (complete response [CR] or partial response [PR])","definition_or_measurement_approach":"ORR measured as proportion of subjects achieving CR or PR per RECIST v1.1 with PCWG3 modifications."}
• {"endpoint_text":"- Phase 2: Duration of response (DOR): time from the assessment of initial response (PR or better) to death or first documented disease progression, whichever occurs first","definition_or_measurement_approach":"DOR measured from time of initial documented response to death or first documented progression."}
• {"endpoint_text":"- Phase 2: Clinical benefit rate (CBR): percentage of subjects with CR, PR, or stable disease (SD) ≥24 weeks","definition_or_measurement_approach":"CBR calculated as percentage of subjects with CR, PR, or SD lasting ≥24 weeks."}
• {"endpoint_text":"- Phase 2: Disease control rate (DCR): percentage of subjects with CR, PR, or SD","definition_or_measurement_approach":"DCR calculated as percentage of subjects achieving CR, PR, or SD."}
• {"endpoint_text":"- Phase 2: Overall Survival (OS) rate at 18 and 24 months","definition_or_measurement_approach":"OS rate at 18 and 24 months estimated using Kaplan–Meier survival analysis."}
• {"endpoint_text":"- Phase 2: Type, incidence, severity (as graded by NCI CTCAE v5.0), seriousness, and relationship to study medications of AEs and any laboratory abnormalities","definition_or_measurement_approach":"AEs and laboratory abnormalities graded per NCI CTCAE v5.0; assessment of type, incidence, severity, seriousness and relationship to study medications."}
• {"endpoint_text":"- Phase 2: PK parameters to be estimated by population PK analysis","definition_or_measurement_approach":"Population pharmacokinetic (PK) analysis to estimate PK parameters of gedatolisib when combined with darolutamide."}

Spain

Earliest CTIS Part Ii Submission Date

22-12-2023

Latest Decision Or Authorization Date

23-12-2025

Processing Time Days

732

Number Of Sites

5

Number Of Participants

25

France

Earliest CTIS Part Ii Submission Date

10-01-2024

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

749

Number Of Sites

4

Number Of Participants

15

Primary sponsor

Full Name

Celcuity Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

code 8

Name

Aperio Clinical Outcomes LLC

Responsibilities

code 6

Name

Suvoda LLC

Responsibilities

code 3

Third parties

• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"code 15 (Patient reimbursement)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Opans LLC","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"code 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Rarecyte Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Bayer AG","duties_or_roles":"code 15 (Darolutamide Owner)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"code 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Aperio Clinical Outcomes LLC","duties_or_roles":"code 6","organisation_type":"Pharmaceutical company"}