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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)

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ClinicalTrials.gov Identifier: NCT03939689
Recruitment Status : Not yet recruiting
First Posted : May 7, 2019
Last Update Posted : May 7, 2019
Sponsor:
Information provided by (Responsible Party):
Progenics Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Metastatic Prostate Cancer Castration-resistant Prostate Cancer Prostatic Neoplasm Cancer of the Prostate Progressive mCRPC Drug: I-131-1095 Drug: Enzalutamide Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 175 participants
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
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
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Active Comparator: Enzalutamide Drug: Enzalutamide
Enzalutamide will be given orally once daily as prescribed by the physician as standard of care.
Other Name: Xtandi

Experimental: I-131-1095 in combination with enzalutamide 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) between 75 mCi - 100 mCi each, administered at least 8 weeks apart as determined by initial 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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Overall survival (OS) [ Time Frame: 24 months ]
    Time from randomization to death from any cause.

  5. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Only male subjects will be enrolled in this study.
Accepts Healthy Volunteers:   No
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 on bone scan
  6. Planned to receive treatment with enzalutamide
  7. Ineligible or choose not to receive taxane-based chemotherapy
  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 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. Hypothyroidism as evidenced by Screening TSH ≥ 4.0 mIU/L with confirmed low Free T4 (< 0.7 ng/dL)
  10. QT interval corrected for heart rate (QTc) > 470 msec
  11. Previous use of enzalutamide for more than 7 days prior to consent
  12. Planned initiation of alternative therapy for prostate cancer, investigational therapy, or participation in clinical trials during the study
  13. History or risk of seizure (i.e., clinically significant neurological disorder) or any other condition that contraindicates treatment with enzalutamide
  14. Gastrointestinal disorder affecting absorption of oral medications
  15. Known or suspected brain metastasis or active leptomeningeal disease
  16. 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
  17. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03939689


Contacts
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Contact: Progenics Clinical Trials Contact 646-975-2554 clinical-trials-contact@Progenics.com

Locations
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Canada, Ontario
London Health Sciences Centre Not yet recruiting
London, Ontario, Canada
Contact: Sarah DeBrabandere    519-685-8500 ext 56399      
Principal Investigator: David Laidley, MD         
Canada, Quebec
Jewish General Hospital Not yet recruiting
Montréal, Quebec, Canada
Contact: Heather Gregory    514-340-8222 ext 26758      
Principal Investigator: Stephan Probst, MD         
Centre Hospitalier Universitaire de Quebec Not yet recruiting
Québec City, Quebec, Canada
Contact: Denise St-Onge    418-525-4444 ext 20414      
Principal Investigator: Frederic Pouliot, MD         
Sponsors and Collaborators
Progenics Pharmaceuticals, Inc.
Investigators
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Study Director: Jessica D Jenssen Progenics Pharmaceuticals, Inc.

Publications:
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Responsible Party: Progenics Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03939689     History of Changes
Other Study ID Numbers: 1095-2301
First Posted: May 7, 2019    Key Record Dates
Last Update Posted: May 7, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Progenics Pharmaceuticals, Inc.:
bone metastases
18F-DCFPyL
PSMA PET
PSMA-avidity
biomarker
radioligand therapy
adjunct radiation therapy
dosimetry
SPECT/CT
docetaxel

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases