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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03939689
Recruitment Status : Recruiting
First Posted : May 7, 2019
Last Update Posted : May 19, 2021
Information provided by (Responsible Party):
Progenics Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE May 3, 2019
First Posted Date  ICMJE May 7, 2019
Last Update Posted Date May 19, 2021
Actual Study Start Date  ICMJE May 30, 2019
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
PSA response rate [ Time Frame: 12 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
  • Objective response rate (ORR) [ Time Frame: 12 months ]
    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.
  • Progression free survival (PFS) [ Time Frame: 24 months ]
    Time from randomization to the first occurrence of radiographic progression, unequivocal clinical progression, or death from any cause.
  • Time to initiation of next treatment for prostate cancer [ Time Frame: 24 months ]
    Time from randomization to initiation of any new treatment for prostate cancer.
  • Overall survival (OS) [ Time Frame: 24 months ]
    Time from randomization to death from any cause.
  • Safety and tolerability of I-131-1095 in combination with enzalutamide: CTCAE v5.0 [ Time Frame: 24 months ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
Brief 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 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
The study population includes patients with PSMA-avid mCRPC whose disease has progressed despite abiraterone therapy, and are planned for treatment with enzalutamide.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Prostate Cancer
  • Castration-resistant Prostate Cancer
  • Prostatic Neoplasm
  • Cancer of the Prostate
  • Progressive mCRPC
Intervention  ICMJE
  • Drug: I-131-1095
    I-131-1095 will be administered intravenously at 100 mCi for the initial therapeutic dose, and up to 3 additional dose(s) at 75 mCi or 100 mCi each, administered at least 8 weeks apart as determined by dosimetry evaluation and occurrence of dose-limiting events.
  • Drug: Enzalutamide
    Enzalutamide will be given orally once daily as prescribed by the physician as standard of care.
    Other Name: Xtandi
Study Arms  ICMJE
  • Active Comparator: Enzalutamide
    Intervention: Drug: Enzalutamide
  • Experimental: I-131-1095 in combination with enzalutamide
    • Drug: I-131-1095
    • Drug: Enzalutamide
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 6, 2019)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: Only male subjects will be enrolled in this study.
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Progenics Clinical Trials Contact 646-975-2521
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03939689
Other Study ID Numbers  ICMJE 1095-2301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Progenics Pharmaceuticals, Inc.
Study Sponsor  ICMJE Progenics Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Istvan Molnar, MD Progenics Pharmaceuticals, Inc.
PRS Account Progenics Pharmaceuticals, Inc.
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP