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 )
Overview
- Phase
- Phase 2
- Intervention
- Enzalutamide
- Conditions
- Metastatic Prostate Cancer
- Sponsor
- Progenics Pharmaceuticals, Inc.
- Enrollment
- 120
- Locations
- 27
- Primary Endpoint
- PSA Response Rate
- Status
- Completed
- Last Updated
- 6 months ago
Overview
Brief 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.
Investigators
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:
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
Arms & Interventions
Enzalutamide
Participants received the label dosage of enzalutamide once daily for up to 53 weeks.
Intervention: Enzalutamide
I-131-1095 in combination with enzalutamide
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 of the 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.
Intervention: I-131-1095
I-131-1095 in combination with enzalutamide
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 of the 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.
Intervention: Enzalutamide
Outcomes
Primary Outcomes
PSA Response Rate
Time Frame: Up to 53 weeks
The percentage of participants with a PSA response according to PCWG3 criteria. PCWG3 defines PSA response as the first occurrence of a 50 percent or more decline in PSA from baseline, confirmed by a second measurement at least 3 weeks later.
Secondary Outcomes
- Objective Response Rate (ORR)(Up to 53 weeks)
- Radiographic Progression Free Survival (rPFS)(Up to 5 years.)
- Overall Survival (OS)(Up to 5 years)
- PSA Progression(Up to 53 weeks)
- Duration of Response(Up to 5 years.)
- Time to Initiation of Next Treatment for Prostate Cancer(Up to 5 years)