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)

Progenics Pharmaceuticals

Status and phase

Active, not recruiting

Phase 2

Conditions

Metastatic Prostate Cancer

Castration-resistant Prostate Cancer

Prostatic Neoplasm

Cancer of the Prostate

Progressive mCRPC

Treatments

Drug: Enzalutamide

Drug: I-131-1095

Study type

Interventional

Funder types

Industry

Identifiers

NCT03939689

1095-2301

Details and patient eligibility

About

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 participants with prostate-specific membrane antigen (PSMA)-avid metastatic castration resistant prostate cancer (mCRPC) who have progressed on abiraterone. Participants 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 participants meeting the PSMA-avidity criteria will be randomized in a 2:1 ratio to receive either I-131-1095 in combination with enzalutamide (80 participants) or enzalutamide alone (40 participants). An interim analysis for efficacy will be performed after a minimum of 48 evaluable participants have PSA data for at least three months following the first dose of randomized treatment.

All participants will be followed for efficacy, safety assessments, survival status, adverse events of special interest, and new anti-cancer therapy for at least one year or to the end of the study (whichever is later) following the first dose of randomized treatment. Safety data will be monitored by an independent Data Monitoring Committee and the sponsor.

Enrollment

120 estimated patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

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:
1. PSA progression as defined by a minimum of two rising PSA levels at least 1 week apart
2. Soft tissue disease progression defined by RECIST 1.1
3. 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:
1. Poor performance status
2. Prior intolerance to cytotoxic agents
3. History of another malignancy suspected for recurrence or metastases
4. 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:
1. Absolute neutrophil count < 1500 μL
2. Platelet count < 100,000/μL
3. Hemoglobin < 9.5 g/dL
4. Albumin < 3.0 g/dL (30 g/L)
5. Total bilirubin > 2 x ULN unless in instances of known or suspected Gilbert's disease
6. AST or ALT > 2.5 x ULN
7. 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.