Clinical trial NCT06395753: A Dose Finding Study of Debio 4228 in Participants With Advanced Prostate Cancer
Official title: A Phase 2, Randomized, Open-Label, Dose-Finding Study of Debio 4228, an Extended-Release Formulation of Gonadotropin-Releasing Hormone Antagonist in Participants With Advanced Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
First posted: 2024-05-02
Enrollment: 66
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of Debio 4228.


Eligibility criteria: Inclusion Criteria:

1. Participant with histologically confirmed diagnosis of prostate cancer, with one of the following:

   1. Newly diagnosed androgen-sensitive locally advanced or metastatic disease; or
   2. Localized disease not suitable for local primary intervention with curative intent.
2. Participant judged by the Study Investigator to be candidate for continuous androgen deprivation therapy (ADT).
3. Baseline morning serum testosterone levels \>150 ng/dL at screening visit.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
5. Life expectancy of at least 6 months.
6. Adequate bone marrow, hepatic, and renal function at the screening visit.

\[Note: Other protocol and subprotocol-defined criteria apply\]

Exclusion Criteria:

1. Previous ADT (neoadjuvant or adjuvant hormonal therapy) for ≥6 months duration and \<6 months treatment-free interval before start of screening.
2. Participant requires combination with androgen deprivation therapy with the exception of enzalutamide.
3. History of bilateral orchiectomy, adrenalectomy, or hypophysectomy.
4. Received chemotherapy or cryotherapy within 8 weeks prior to the start of screening for the treatment of prostate cancer.
5. Abnormal cardiovascular function or diabetes.
6. Use of exogenous testosterone within 6 months before the start of screening.
7. Major surgery within 4 weeks before the start of screening.
8. Cancer disease within the last two years except for prostate cancer and some skin cancers.

\[Note: Other protocol and subprotocol-defined criteria apply\]

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Debio 4228
timeFrame: Cohorts 1 and 2: Predose and at multiple time points post-dose up to Day 169; Cohort 3: Predose and at multiple time points post-dose up to Day 169
measure: Area Under the Concentration-time Curve of Debio 4228 Over 12 weeks (AUC84d)
timeFrame: Cohorts 1 and 2: Predose and at multiple time points post-dose up to Day 84; Cohort 3: Predose and at multiple time points post-dose up to Day 169
measure: Plasma Concentration of Debio 4228 at Week 12 (C84d)
timeFrame: Cohorts 1 and 2: Post-dose on Day 84; Cohort 3: Post-dose on Days 84 and 168
measure: Serum Concentration of Testosterone
timeFrame: Cohorts 1 and 2: Predose and at multiple time points post-dose from Days 1 to 85; Cohort 3: Predose and at multiple time points post-dose from Days 1 to 169
Secondary outcomes:
measure: Number of Participants who Achieved and Maintained a Testosterone Castration (Testosterone Level of <50 [Nanograms per Deciliter] ng/dL and <20 ng/dL)
timeFrame: Cohorts 1, 2, and 3: Days 29 to 85
measure: Number of Participants who Maintained a Testosterone Castration (Testosterone Level of <50 ng/dL and <20 ng/dL)
timeFrame: Cohort 3: Days 29 to 169
measure: Time to Achieve Testosterone Castration (Testosterone Level of <50 ng/dL and <20 ng/dL)
timeFrame: Cohorts 1 and 2: Day 1 up to Day 85; Cohort 3: Day 1 up to Day 169
measure: Number of Participants who Experience Local Reactions Categorized as Erythema, Swelling, and Induration at the Injection Site
timeFrame: Cohorts 1 and 2: Immediately, at 2 and 24 hours post-injection on Day 1; Cohort 3: Immediately, at 2 and 24 hours post-injection on Days 1 and 85
measure: Number of Participants who Experience Pain at Injection Site
timeFrame: Cohorts 1 and 2: Immediately, at 2 and 24 hours post-injection on Day 1; Cohort 3: Immediately, at 2 and 24 hours post-injection on Days 1 and 85
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity
timeFrame: Cohorts 1 and 2: Up to Day 169; Cohort 3: Up to Day 197
measure: Number of Participants With Related TEAEs, Serious TEAEs, Adverse Events of Special Interest (AESIs), TEAEs Leading to Treatment Delay, and/or Discontinuation, and Death
timeFrame: Cohorts 1 and 2: Up to Day 169; Cohort 3: Up to Day 197
measure: Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, and Electrocardiogram (ECG) Parameters
timeFrame: Cohorts 1 and 2: Up to Day 169; Cohort 3: Up to Day 197
measure: Percent Change From Baseline in Serum Prostate-Specific Antigen (PSA) Over Time
timeFrame: Cohorts 1 and 2: Baseline up to Day 85; Cohort 3: Baseline up to Day 169
measure: Change From Baseline of Serum Luteinizing Hormone (LH) Over Time
timeFrame: Cohorts 1 and 2: Baseline up to Day 85; Cohort 3: Baseline up to Day 169
measure: Change From Baseline in Serum Follicle-Stimulating Hormone (FSH) Over Time
timeFrame: Cohorts 1 and 2: Baseline up to Day 85; Cohort 3: Baseline up to Day 169
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Bakersfield Institute of Advanced Urology
state: California
city: Fresno
country: United States
facility: Valley Urology
state: California
city: Los Angeles
country: United States
facility: Advanced Urology
state: California
city: Los Angeles
country: United States
facility: Tower Urology,
state: California
city: Murrieta
country: United States
facility: Urology Center of Southern California
state: California
city: Miami
country: United States
facility: AP Medical Research
state: Florida
city: Miami
country: United States
facility: Biogenix Molecular
state: Florida
city: Jeffersonville
country: United States
facility: First Urology- Jeffersonville
state: Indiana
city: Wichita
country: United States
facility: GU Research Network/Wichita Urology Group
state: Kansas
city: Shirley
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Raleigh
country: United States
facility: Associated Urologists of North Carolina
state: North Carolina
city: Springfield
country: United States
facility: Oregon Urology Institut
state: Oregon
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Dallas
country: United States
facility: Urology Clinics of North Texas
state: Texas
city: Virginia Beach
country: United States
facility: Urology of Virginia
state: Virginia
city: Spokane
country: United States
facility: Summit Cancer Centers of North Spokane
state: Washington
city: Gent
country: Belgium
facility: University Hospital Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Roeselare
country: Belgium
facility: AZ Delta
city: Angers
country: France
facility: CHU Angers
city: Brest
country: France
facility: CHRU de Brest - Hopital Morvan
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Nantes
country: France
facility: CHU de Nantes - Hôtel Dieu
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madroñera
country: Spain
facility: Hospital Clinico San Carlos
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
Study officials:
References: