Study of I-131-1095 molecular Radiotherapy in Combination With Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Who Are Chemotherapy Naïve and Have Progressed on Abiraterone - Arrow Study
Lay Title: A randomized trial to evaluate the effects of molecular radiotherapy in combination with Enzalutamide in patients with progressive disease.
Technical Title: A Multicenter, Randomized, Controlled Phase 2 Study: Efficacy and Safety of I-131-1095 molecular Radiotherapy in Combination With Enzalutamide in Metastatic Castration-resistant Prostate Cancer.
Disease Type: Metastatic castrate-resistant prostate cancer (mCRPC)
Basic information: This is a multicenter, randomized, controlled, phase 2 clinical trial designed to evaluate the safety and efficacy of I-131-1095 molecular 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.
Research Procedures: This trial will include about 30 participating study center and as a whole will enroll an estimated 120 patients with mCRPC whose disease has progressed despite abiraterone therapy, and are planned for treatment with enzalutamide.
All patients will be randomized to either:
- I-131-1095 plus enzalutamide (80 patients)
- Enzalutamide alone (40 patients)
The study period will be approximately 5 years total durations. All patients will undergo a PSMA imaging with 18F-DCFPyL PET/CT during the screening process to confirm high PSMA expression. During the randomization period, all patients will be followed for 1 year following first dose of treatment with included prostate cancer assessments.
Subjects must also be screened for 18F-DCFPyL avidity as defined by the below criteria to proceed to Randomization:
- 18F-DCFPyL PET/CT imaging shows significant PSMA uptake (SUVmax > 1x liver SUVmean) in all prostate cancer lesions, except as noted below:
- PSMA negative soft tissue lesions < 1.0 cm in short axis;
- PSMA negative lymph node lesions < 1.5 cm in short axis;
- PSMA negative bone lesions with a soft tissue component < 1.0 cm in short axis or without a soft tissue component of any size
- Adult male 18 years or older;
- Histologically or cytologically proven prostate cancer;
- Castration-resistant prostate cancer, with serum testosterone ≤ 50 ng/dL (1.73 nM) at Screening
- Metastatic disease documented by bone lesions on whole body bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI prior to Randomization or up to 21 days prior to Screening
- Evidence of disease progression on prior abiraterone therapy. Disease progression is defined by meeting at least one of the following criteria:
- 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 for 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 bisphosphonates must have been on stable doses for ≥ 4 weeks prior to Randomization
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- If sexually active, agree to use a medically acceptable method of birth control (e.g., spermicide in conjunction with a barrier such as a condom) or sexual abstinence from the time of dosing through 28 days after the last dose of I-131-1095. Sperm donation is prohibited 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 or treating physician
- Able and willing to provide signed informed consent and comply with protocol requirements
- Received any anti-tumor therapy within 4 weeks of Randomization, with the exception of abiraterone, gonadotropic-releasing hormone (GnRH) therapy and non-radioactive bone-targeted agents
- Received prior chemotherapy for castration-resistant prostate cancer (CRPC)
- 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 in Screening labs:
- 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 and 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 during Screening
- Previous use of enzalutamide for >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 (Xtandi®) as per the package insert
- 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.
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