Clinical Trials /

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

NCT03939689

Description:

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 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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: A Multicenter, Randomized, Controlled Phase 2 Study: Efficacy and Safety of I-131-1095 Radiotherapy in Combination With Enzalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients Who Are 18F-DCFPyL Prostate-specific Membrane Antigen (PSMA)-Avid, Chemotherapy-naive, and Progressed on Abiraterone

Clinical Trial IDs

  • ORG STUDY ID: 1095-2301
  • NCT ID: NCT03939689

Conditions

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

Interventions

DrugSynonymsArms
I-131-1095I-131-1095 in combination with enzalutamide
EnzalutamideXtandiEnzalutamide

Purpose

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 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.

Trial Arms

NameTypeDescriptionInterventions
EnzalutamideActive Comparator
  • Enzalutamide
I-131-1095 in combination with enzalutamideExperimental
  • I-131-1095
  • Enzalutamide

Eligibility Criteria

        Inclusion Criteria:

          1. Male ≥ 18 years of age

          2. Histologically or cytologically confirmed adenocarcinoma of the prostate without
             neuroendocrine differentiation or small cell features at initial diagnosis

          3. Castration-resistant prostate cancer, with serum testosterone ≤ 50 ng/dL at Screening

          4. Radiographic evidence of metastatic disease prior to Randomization or up to 21 days
             prior to Screening

          5. 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

          6. Planned to receive treatment with enzalutamide

          7. 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

          8. Subjects receiving bisphosphonate therapy must have been on stable doses for at least
             4 weeks prior to Randomization

          9. ECOG performance status 0-2

         10. 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.

         11. Estimated life expectancy of at least 6 months as determined by the Investigator.

         12. Able and willing to provide signed informed consent and comply with protocol
             requirements

        Exclusion Criteria:

          1. Received any anti-tumor therapy within 4 weeks of Randomization, with the exception of
             abiraterone, GnRH therapy and non-radioactive bone-targeted agents

          2. Received prior chemotherapy for castration-resistant prostate cancer

          3. Superscan as evidenced on baseline bone scan

          4. Treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 within
             6 months prior to Randomization

          5. Prior hemi-body irradiation

          6. Prior PSMA-targeted radioligand therapy

          7. Major surgery within 4 weeks of Randomization

          8. 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.

          9. QT interval corrected for heart rate (QTc) > 470 msec

         10. Previous use of enzalutamide for more than 7 days prior to consent

         11. Planned initiation of alternative therapy for prostate cancer, investigational
             therapy, or participation in clinical trials during the study

         12. History or risk of seizure (i.e., clinically significant neurological disorder) or any
             other condition that contraindicates treatment with enzalutamide

         13. Gastrointestinal disorder affecting absorption of oral medications

         14. Known or suspected brain metastasis or active leptomeningeal disease

         15. 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

         16. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:PSA response rate
Time Frame:12 months
Safety Issue:
Description:The proportion of patients with PSA response according to PCWG3 criteria defined as the first occurrence of a 50% or more decline in PSA from baseline, confirmed by a second measurement at least 3 weeks later.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:12 months
Safety Issue:
Description:The proportion of patients with complete or partial response based on RECIST 1.1 for soft tissue or PCWG3-modified RECIST 1.1 for bone.
Measure:Progression free survival (PFS)
Time Frame:24 months
Safety Issue:
Description:Time from randomization to the first occurrence of radiographic progression, unequivocal clinical progression, or death from any cause.
Measure:Time to initiation of next treatment for prostate cancer
Time Frame:24 months
Safety Issue:
Description:Time from randomization to initiation of any new treatment for prostate cancer.
Measure:Overall survival (OS)
Time Frame:24 months
Safety Issue:
Description:Time from randomization to death from any cause.
Measure:Safety and tolerability of I-131-1095 in combination with enzalutamide: CTCAE v5.0
Time Frame:24 months
Safety Issue:
Description:Percentage of patients with treatment-emergent adverse events based on incidence of treatment-emergent adverse events and serious adverse events measured by CTCAE v5.0.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Progenics Pharmaceuticals, Inc.

Trial Keywords

  • bone metastases
  • 18F-DCFPyL
  • PSMA PET
  • PSMA-avidity
  • biomarker
  • radioligand therapy
  • adjunct radiation therapy
  • dosimetry
  • SPECT/CT
  • docetaxel

Last Updated

April 8, 2020