Trial Title:
Gedatolisib in Combination With Darolutamide in Metastatic Castration-Resistant Prostate Cancer
NCT ID:
NCT06190899
Condition:
mCRPC (Metastatic Castration-resistant Prostate Cancer)
Genital Diseases, Male
Urogenital Diseases, Male
Prostatic Disease
Prostatic Neoplasms, Castration-Resistant
Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Prostatic Neoplasms, Castration-Resistant
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Genital Diseases, Male
Male Urogenital Diseases
Gedatolisib
Conditions: Keywords:
Gedatolisib
PI3K
Protein Kinase Inhibitors
mCRPC (metastatic castration-resistant prostate cancer)
Darolutamide
Prostate Cancer
Prostatic Neoplasms, Castration-Resistant
Prostatic Disease
Urogenital Diseases, Male
Genital Diseases, Male
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
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 purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Gedatolisib
Description:
Gedatolisib is a potent reversible inhibitor that selectively targets all Class I PI3K
isoforms and mTOR.
Arm group label:
Phase 1 Arm 1
Arm group label:
Phase 1 Arm 2
Arm group label:
Phase 2
Intervention type:
Drug
Intervention name:
Darolutamide
Description:
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.
Arm group label:
Phase 1 Arm 1
Arm group label:
Phase 1 Arm 2
Arm group label:
Phase 2
Other name:
NUBEQA
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.
Detailed 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.
Criteria for 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
Gender:
Male
Gender based:
Yes
Gender description:
Adult Males
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Barbara Ann Karmanos Cancer Institute
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Facility:
Name:
Centre Jean Perrin
Address:
City:
Clermont-Ferrand
Zip:
63011
Country:
France
Status:
Not yet recruiting
Facility:
Name:
Institut Paoli-Calmettes
Address:
City:
Marseille
Zip:
13009
Country:
France
Status:
Not yet recruiting
Facility:
Name:
Centre Antoine Lacassagne
Address:
City:
Nice
Zip:
06100
Country:
France
Status:
Not yet recruiting
Facility:
Name:
Institut Gustave Roussy
Address:
City:
Villejuif
Zip:
94805
Country:
France
Status:
Not yet recruiting
Facility:
Name:
Hospital Clinic Barcelona
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Status:
Recruiting
Facility:
Name:
Institut Catala d'Oncologia
Address:
City:
Barcelona
Zip:
08908
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital General Universitario Gregorio Maranon
Address:
City:
Madrid
Zip:
28007
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Hospital 12 de Octubre
Address:
City:
Madrid
Zip:
28045
Country:
Spain
Status:
Recruiting
Facility:
Name:
Instituto Valenciano de Oncología
Address:
City:
Valencia
Zip:
46009
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospita
Address:
City:
Cambridge
Zip:
CB20QQ
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
University Hospital Southampton NHS Foundation Trust - Southampton General Hospital
Address:
City:
Southampton
Zip:
SO16 6YD
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
Royal Marsden NHS Foundation Trust
Address:
City:
Sutton
Zip:
SM25PT
Country:
United Kingdom
Status:
Recruiting
Start date:
January 1, 2024
Completion date:
November 2027
Lead sponsor:
Agency:
Celcuity Inc
Agency class:
Industry
Source:
Celcuity Inc
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06190899
