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Study of I-131-1095 Radiotherapy in Combination With Enzalutamide in Patients With Metastatic Castration-resistant Prostate Cancer Who Are Chemotherapy Naive and Have Progressed on Abiraterone

Trial Status: Active

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.

Inclusion Criteria

  • Male ≥ 18 years of age
  • Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features at initial diagnosis
  • Castration-resistant prostate cancer, with serum testosterone ≤ 50 ng/dL at Screening
  • Radiographic evidence of metastatic disease prior to Randomization or up to 21 days prior to Screening
  • Disease progression on prior abiraterone therapy as defined by meeting at least one of the following criteria per the investigator:
  • PSA progression as defined by a minimum of two rising PSA levels at least 1 week apart
  • Soft tissue disease progression defined by RECIST 1.1
  • Bone disease progression defined by two or more new lesions on bone scan
  • Planned to receive treatment with enzalutamide
  • 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:
  • Poor performance status
  • Prior intolerance to cytotoxic agents
  • History of another malignancy suspected for recurrence or metastases
  • 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
  • Subjects receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks prior to Randomization
  • ECOG performance status 0-2
  • 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-131-1095. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent.
  • Estimated life expectancy of at least 6 months as determined by the Investigator.
  • Able and willing to provide signed informed consent and comply with protocol requirements

Exclusion Criteria

  • Received any anti-tumor therapy within 4 weeks of Randomization, with the exception of abiraterone, GnRH therapy and non-radioactive bone-targeted agents
  • Received prior chemotherapy for castration-resistant prostate cancer
  • Superscan as evidenced on baseline bone scan
  • Treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 within 6 months prior to Randomization
  • Prior hemi-body irradiation
  • Prior PSMA-targeted radioligand therapy
  • Major surgery within 4 weeks of Randomization
  • Impaired organ function as evidenced by the following laboratory values at Screening:
  • Absolute neutrophil count < 1500 μL
  • Platelet count < 100,000/μL
  • Hemoglobin < 9.5 g/dL
  • Albumin < 3.0 g/dL (30 g/L)
  • Total bilirubin > 2 x ULN unless in instances of known or suspected Gilbert's disease
  • AST or ALT > 2.5 x ULN
  • Calculated creatinine clearance (CrCL) < 30 mL/min (Cockroft-Gault equation), or currently on renal dialysis.
  • QT interval corrected for heart rate (QTc) > 470 msec
  • Previous use of enzalutamide for more than 7 days prior to consent
  • Planned initiation of alternative therapy for prostate cancer, investigational therapy, or participation in clinical trials during the study
  • History or risk of seizure (i.e., clinically significant neurological disorder) or any other condition that contraindicates treatment with enzalutamide
  • Gastrointestinal disorder affecting absorption of oral medications
  • Known or suspected brain metastasis or active leptomeningeal disease
  • 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
  • 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.


City of Hope Comprehensive Cancer Center
Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: ACTIVE
Contact: Soosan Roodbari
Phone: 310-794-1596

District of Columbia

MedStar Georgetown University Hospital
Status: ACTIVE


University of Chicago Comprehensive Cancer Center
Status: ACTIVE


University of Maryland / Greenebaum Cancer Center
Status: ACTIVE
Contact: Jill Harper
Phone: 410-369-5350


Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: ACTIVE


Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE


University of Pennsylvania / Abramson Cancer Center
Status: ACTIVE

South Carolina

Medical University of South Carolina
Status: ACTIVE


M D Anderson Cancer Center
Status: ACTIVE


University of Virginia Cancer Center
Status: ACTIVE


Fred Hutch / University of Washington Cancer Consortium
Status: ACTIVE

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Progenics Pharmaceuticals, Inc.

  • Primary ID 1095-2301
  • Secondary IDs NCI-2019-03770
  • ID NCT03939689