I-131-1095 Radioligand Plus Enzalutamide vs Enzalutamide for mCRPC That Progressed During Abiraterone (ARROW).

Prior treatment

• 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
• 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
• 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

Other illness

• 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.

Lab values

• 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

Other

• Superscan as evidenced on baseline bone scan

• 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