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 (ARROW)
Metastatic Prostate Cancer, Castration-resistant Prostate Cancer, Prostatic Neoplasm
About this trial
This is an interventional treatment trial for Metastatic Prostate Cancer focused on measuring bone metastases, 18F-DCFPyL, PSMA PET, PSMA-avidity, biomarker, radioligand therapy, adjunct radiation therapy, dosimetry, SPECT/CT, docetaxel
Eligibility Criteria
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.
Sites / Locations
- City of Hope
- VA Greater Los Angeles Healthcare System
- UCLA
- Hoag Family Cancer Institute
- VA Palo Alto Healthcare System
- Medstar Georgetown University Hospital
- The University of Chicago
- University of Iowa
- Tulane Medical School
- University of Maryland
- University of Michigan Comprehensive Cancer Center
- Washington University School of Medicine
- SUNY Upstate Medical University
- University of Pennsylvania
- LifeSpan Cancer Institute
- Medical University of South Carolina
- University of Texas MD Anderson Cancer Center
- University of Virginia Cancer Center
- Virginia Mason Medical Center
- University of Washington - Seattle Cancer Care Alliance
- The Ottawa Hospital
- London Health Sciences Centre
- University Health Network - Princess Margaret Cancer Centre
- Centre Hospitalier Del' Universite de Montreal
- Jewish General Hospital
- Centre Hospitalier Universitaire de Quebec
- Centre Hospitalier Universitaire de Sherbrooke
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Enzalutamide
I-131-1095 in combination with enzalutamide