Summary

Eligibility
for males ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
completion around
Principal Investigator
by Jeremie Calais (ucla)
Headshot of Jeremie Calais
Jeremie Calais

Description

Summary

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.

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

Keywords

Metastatic Prostate Cancer, Castration-resistant Prostate Cancer, Prostatic Neoplasm, Cancer of the Prostate, Progressive mCRPC, bone metastases, 18F-DCFPyL, PSMA PET, PSMA-avidity, biomarker, radioligand therapy, adjunct radiation therapy, dosimetry, SPECT/CT, docetaxel, Prostatic Neoplasms, Enzalutamide

Eligibility

You can join if…

Open to males ages 18 years and up

  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

You CAN'T join if...

  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.

Locations

  • UCLA
    Los Angeles California 90095-7370 United States
  • Hoag Family Cancer Institute
    Newport Beach California 92663 United States
  • VA Greater Los Angeles Healthcare System
    Los Angeles California 90073 United States
  • VA Palo Alto Healthcare System
    Palo Alto California 94303 United States
  • City of Hope
    Duarte California 91010 United States

Lead Scientist at University of California Health

  • Jeremie Calais (ucla)
    Nuclear medicine physician specialized in cancer imaging and theranostics. Associate Professor, Department of Molecular and Medical Pharmacology at UCLA Director, Theranostics Program, Ahmanson Translational Theranostics Division at UCLA Faculty Member of the Jonsson Comprehensive Cancer Center at UCLA. Faculty Member of the Institute of Urologic Oncology at UCLA.

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Progenics Pharmaceuticals, Inc.
ID
NCT03939689
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 120 study participants
Last Updated