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 (PSMA)-Avid, Chemotherapy-naive, and Progressed on Abiraterone


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 defined by two or more new lesions on bone scan
  9. Planned to receive treatment with enzalutamide
  10. Subjects who are ineligible or choose not to receive taxane-based chemotherapy based on personal preference or physician opinion. Examples of conditions that could make a patient ineligible or refuse to receive taxane-based chemotherapy, but would allow them to still be eligible to receive I-131-1095 include the following:
  11. Poor performance status
  12. Prior intolerance to cytotoxic agents
  13. History of another malignancy suspected for recurrence or metastases
  14. Other serious medical conditions such as symptomatic peripheral neuropathy CTCAE Grade 2 or higher; or clinically significant cardiovascular disease per the Investigator or treating physician
  15. Subjects receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks prior to Randomization
  16. ECOG performance status 0-2
  17. 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
  18. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent.
  19. Estimated life expectancy of at least 6 months as determined by the Investigator.
  20. 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 castration-resistant 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. QT interval corrected for heart rate (QTc) > 470 msec
  17. Previous use of enzalutamide for more than 7 days prior to consent
  18. Planned initiation of alternative therapy for prostate cancer, investigational therapy, or participation in clinical trials during the study
  19. History or risk of seizure (i.e., clinically significant neurological disorder) or any other condition that contraindicates treatment with enzalutamide
  20. Gastrointestinal disorder affecting absorption of oral medications
  21. Known or suspected brain metastasis or active leptomeningeal disease
  22. 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
  23. 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:

  • VA Greater Los Angeles Healthcare System
  • Los Angeles California 90073 United States
  • Medstar Georgetown University Hospital
  • Washington District of Columbia 20007 United States
  • The University of Chicago
  • Chicago Illinois 60637 United States
  • University of Michigan Comprehensive Cancer Center
  • Ann Arbor Michigan 48109 United States
  • Washington University School of Medicine
  • Saint Louis Missouri 63110 United States
  • University of Virginia Cancer Center
  • Charlottesville Virginia 22908 United States
  • London Health Sciences Centre
  • Toronto Ontario Canada
  • University Health Network - Princess Margaret Cancer Centre
  • Toronto Ontario Canada
  • Centre Hospitalier Del' Universite de Montreal
  • Montreal Quebec Canada
  • Jewish General Hospital
  • Montreal Quebec Canada
  • Centre Hospitalier Universitaire de Quebec
  • Quebec City Quebec Canada
  • Centre Hospitalier Universitaire de Sherbrooke
  • Sherbrooke Quebec Canada

View trial on ClinicalTrials.gov