NCT03939689

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

A Multicenter, Randomized, Controlled Phase 2 Study: Efficacy and Safety of I-131-1095 Radiotherapy in Combination With Enzalutamide in mCRPC Patients Who Are 18F-DCFPyL PSMA-avid, Chemotherapy-naïve, and Progressed on Abiraterone (ARROW )

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (actual)
• Sponsor: Progenics Pharmaceuticals, Inc. · Industry
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This clinical trial was done to show whether a radioactive drug (I-131-1095) that binds to prostate-specific membrane antigen (PSMA) is useful in treating metastatic prostate cancer that is positive for PSMA. The trial enrolled men whose PSMA-positive metastatic prostate cancer had progressed while they were taking abiraterone. During the trial, all of the men took enzalutamide (standard-of-care therapy) once a day. However, some of the men also had up to 4 doses (8 weeks apart) of I-131-1095 (in addition to taking enzalutamide once a day). At specified times during the trial, all of the men had blood tests (to measure levels of prostate-specific antigen \[PSA\]) and imaging studies (to assess tumor status). The two groups of men were then compared in several ways. The main comparison was the percentage of men in each group with at least a 50% decrease in PSA levels. Other comparisons involved the response of the tumors (as seen on imaging) and overall survival. To assess safety, the number of adverse events in both groups were also compared.

Detailed description

This phase 2 clinical trial (conducted in the United States and Canada) enrolled chemotherapy-naïve men whose PSMA-positive (as shown by piflufolastat F18 imaging) metastatic prostate cancer had progressed during treatment with abiraterone. The participants were stratified by risk factors at Screening and then randomized 2:1 either to receive PSMA radioligand therapy (up to four 8-week cycles of I-131-1095) plus standard treatment with enzalutamide or to receive standard treatment with enzalutamide as monotherapy. The prostate-specific antigen (PSA) levels and radiographic response or progression (RECIST v1.1 criteria for soft tissue and PCWG3 criteria for bone) were then monitored for up to 53 weeks of randomized treatment. The primary outcome measure was PSA response rate (percentage of participants with a confirmed ≥50% decrease in serum PSA). Other outcome measures included percentage of participants with partial or complete response (radiographic), duration of response, time to progression (PSA or radiographic), time to next treatment for prostate cancer, and overall survival.

Conditions

• Metastatic Prostate Cancer
• Castration-resistant Prostate Cancer
• Prostatic Neoplasm
• Cancer of the Prostate
• Progressive mCRPC

Interventions

Type	Name	Description
DRUG	I-131-1095	Participants received up to 4 (8-week) cycles of I-131-1095: 100 mCi for the first dose. Subsequent dose(s) were reduced to 75 mCi for participants experiencing any dose-limiting toxicities. The third and fourth therapeutic doses could be reduced to 75 mCi on the basis of dosimetry assessment after administration of 10 mCi of I-131-1095 prior to the third dosing cycle. Participants also received the label dosage of enzalutamide once daily for up to 53 weeks.
DRUG	Enzalutamide	Participants received the label dosage of enzalutamide once daily for up to 53 weeks.

Timeline

• Start date: 2019-05-30
• Primary completion: 2023-09-21
• Completion: 2024-09-24
• First posted: 2019-05-07
• Last updated: 2025-10-14
• Results posted: 2025-10-14

Locations

27 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study