A Multicenter, Randomized, Controlled Phase 2 Study: Efficacy and Safety of I-131-1095 Radiotherapy in Combination With Enzalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients Who Are 18F-DCFPyL Prostate-specific Membrane Antigen

Condition: Metastatic Prostate Cancer, Castration-resistant Prostate Cancer, Prostatic Neoplasm, Cancer of the Prostate, Progressive mCRPC

Intervention:

• Drug: I-131-1095
• Drug: Enzalutamide

Purpose: This is a multicenter, randomized, controlled, phase 2 clinical trial designed to evaluate the safety and efficacy of I-131-1095 radiotherapy in combination with enzalutamide compared to enzalutamide alone in patients with prostate-specific membrane antigen (PSMA)-avid metastatic castration resistant prostate cancer (mCRPC) who have progressed on abiraterone. Patients must be chemotherapy-naive and must be ineligible or refuse to receive taxane-based chemotherapy at time of study entry. PSMA-avidity will be determined by central imaging review based on assessment of 18F-DCFPyL PET/CT imaging during screening. Eligible patients meeting the PSMA-avidity criteria will be randomized in a 2:1 ratio to receive either I-131-1095 in combination with enzalutamide (80 subjects) or enzalutamide alone (40 subjects). Patients will be followed for efficacy and safety assessments during a 12-month Randomized Treatment period. Patients will be followed for an additional year for safety and survival status. Safety data will be monitored by an independent Data Monitoring Committee and the sponsor.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03939689

Sponsor: Progenics Pharmaceuticals, Inc.

Primary Outcome Measures:

• Measure: PSA response rate
• Time Frame: 12 months
• Safety Issue:

Secondary Outcome Measures:

• Measure: Objective response rate (ORR)
• Time Frame: 12 months
• Safety Issue:
• Measure: Progression free survival (PFS)
• Time Frame: 24 months
• Safety Issue:
• Measure: Time to initiation of next treatment for prostate cancer
• Time Frame: 24 months
• Safety Issue:
• Measure: Overall survival (OS)
• Time Frame: 24 months
• Safety Issue:
• Measure: Safety and tolerability of I-131-1095 in combination with enzalutamide: CTCAE v5.0
• Time Frame: 24 months
• Safety Issue:

Estimated Enrollment: 175

Study Start Date: May 30, 2019

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

1. Male ≥ 18 years of age
2. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features at initial diagnosis
3. Castration-resistant prostate cancer, with serum testosterone ≤ 50 ng/dL at Screening
4. Radiographic evidence of metastatic disease prior to Randomization or up to 21 days prior to Screening
5. Disease progression on prior abiraterone therapy as defined by meeting at least one of the following criteria per the investigator:
6. PSA progression as defined by a minimum of two rising PSA levels at least 1 week apart
7. Soft tissue disease progression defined by RECIST 1.1
8. Bone disease progression on bone scan
9. Planned to receive treatment with enzalutamide
10. Ineligible or choose not to receive taxane-based chemotherapy
11. Subjects receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks prior to Randomization
12. ECOG performance status 0-2
13. If sexually active, agree to use a medically acceptable method of birth control or sexual abstinence from the time of dosing through 28 days after the last dose of I-131-10
14. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent.
15. Estimated life expectancy of at least 6 months as determined by the Investigator.
16. Able and willing to provide signed informed consent and comply with protocol requirements

Exclusion Criteria:

1. Received any anti-tumor therapy within 4 weeks of Randomization, with the exception of abiraterone, GnRH therapy and non-radioactive bone-targeted agents
2. Received prior chemotherapy for prostate cancer
3. Superscan as evidenced on baseline bone scan
4. Treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 within 6 months prior to Randomization
5. Prior hemi-body irradiation
6. Prior PSMA-targeted radioligand therapy
7. Major surgery within 4 weeks of Randomization
8. Impaired organ function as evidenced by the following laboratory values at Screening:
9. Absolute neutrophil count < 1500 μL
10. Platelet count < 100,000/μL
11. Hemoglobin < 9.5 g/dL
12. Albumin < 3.0 g/dL (30 g/L)
13. Total bilirubin > 2 x ULN unless in instances of known or suspected Gilbert’s disease
14. AST or ALT > 2.5 x ULN
15. Calculated creatinine clearance (CrCL) < 30 mL/min (Cockroft-Gault equation), or currently on renal dialysis.
16. Hypothyroidism as evidenced by Screening TSH ≥ 4.0 mIU/L with confirmed low Free T4 (< 0.7 ng/dL)
17. QT interval corrected for heart rate (QTc) > 470 msec
18. Previous use of enzalutamide for more than 7 days prior to consent
19. Planned initiation of alternative therapy for prostate cancer, investigational therapy, or participation in clinical trials during the study
20. History or risk of seizure (i.e., clinically significant neurological disorder) or any other condition that contraindicates treatment with enzalutamide
21. Gastrointestinal disorder affecting absorption of oral medications
22. Known or suspected brain metastasis or active leptomeningeal disease
23. Active malignancy other than prostate cancer, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or non-muscle invasive bladder/urothelial cancer
24. Subjects with any medical condition or other circumstances that, in the opinion of the investigator, compromise obtaining reliable data, achieving study objectives, or completing the study.

Contact:

• Progenics Clinical Trials Contact
• 646-975-2554

Locations:

• London Health Sciences Centre
• London Ontario Canada

• Jewish General Hospital
• Montréal Quebec Canada

• Centre Hospitalier Universitaire de Quebec
• Québec City Quebec Canada

View trial on ClinicalTrials.gov