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

Metastatic Prostate Cancer Clinical Trial

— ARROW  

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03939689
• Other study ID #: 1095-2301
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 30, 2019
• Est. completion date: September 24, 2024

Study information

• Verified date: November 2023
• Source: Progenics Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: September 24, 2024
• Est. primary completion date: September 21, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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.
• Enzalutamide
Enzalutamide will be given orally once daily as prescribed by the physician as standard of care.

Locations

Country	Name	City	State
Canada	Centre Hospitalier Del' Universite de Montreal	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	London Health Sciences Centre	Toronto	Ontario
Canada	University Health Network - Princess Margaret Cancer Centre	Toronto	Ontario
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Maryland	Baltimore	Maryland
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	The University of Chicago	Chicago	Illinois
United States	City of Hope	Duarte	California
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	UCLA	Los Angeles	California
United States	VA Greater Los Angeles Healthcare System	Los Angeles	California
United States	Tulane Medical School	New Orleans	Louisiana
United States	Hoag Family Cancer Institute	Newport Beach	California
United States	VA Palo Alto Healthcare System	Palo Alto	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	LifeSpan Cancer Institute	Providence	Rhode Island
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Washington - Seattle Cancer Care Alliance	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Medstar Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Progenics Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

Afshar-Oromieh A, Haberkorn U, Zechmann C, Armor T, Mier W, Spohn F, Debus N, Holland-Letz T, Babich J, Kratochwil C. Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with 131I-MIP-1095. Eur J Nucl Med Mol Imaging. 2017 Jun;44(6):950-959. doi: 10.1007/s00259-017-3665-9. Epub 2017 Mar 9. — View Citation

Zechmann CM, Afshar-Oromieh A, Armor T, Stubbs JB, Mier W, Hadaschik B, Joyal J, Kopka K, Debus J, Babich JW, Haberkorn U. Radiation dosimetry and first therapy results with a (124)I/ (131)I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy. Eur J Nucl Med Mol Imaging. 2014 Jul;41(7):1280-92. doi: 10.1007/s00259-014-2713-y. Epub 2014 Feb 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PSA Response Rate	The proportion of participants with a PSA response according to PCWG3 criteria defined 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.	Up to 53 weeks
Secondary	Objective Response Rate (ORR)	The proportion of participants who have a partial response (PR) or complete response (CR) based on RECIST 1.1 for soft tissue or PCWG3 for bone (PCWG3-modified RECIST 1.1).	Up to 53 weeks
Secondary	Radiographic Progression Free Survival (rPFS)	Time from randomization to the first occurrence of radiographic progression based on RECIST 1.1 for soft tissue or PCWG3-modified RECIST 1.1 for bone, respectively, or unequivocal clinical progression, or death on study from any cause.	Up to 53 weeks
Secondary	Overall Survival (OS)	Overall Survival is defined as time from randomization to death from any cause.	Up to 5 years
Secondary	PSA Progression	Time from randomization to the date of the first PSA increase from baseline = 25 percent and = 2 ng/ml above nadir confirmed by a second PSA assessment defining progression = 3 weeks later per PCWG3.	Up to 53 weeks
Secondary	Duration Of Response	Time from the first date of complete response (CR) or partial response (PR) to the first occurrence of radiographic progression based on PCWG3-modified RECIST 1.1, or unequivocal clinical progression.	Up to 53 weeks
Secondary	Time To Initiation Of Next Treatment For Prostate Cancer	Time from randomization to initiation of any new treatment for prostate cancer.	Up to 5 years
Secondary	Incidences Of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events As Assessed by CTCAE v5.0 (Safety Outcome Measure)	TEAEs will be summarized by SOC and PT using the frequency and percentage of participants experiencing any adverse event, experiencing each SOC and experiencing each PT within each SOC.	After first administration of study drug to visit week 53
Secondary	Adverse Events Resulting In Discontinuation Of Study Drug (Safety Outcome Measure)	A high-level summary of TEAEs will be presented for participants who had at least one TEAE overall, seriousness, and leading to discontinuation of treatment.	After first administration of study drug to visit week 53
Secondary	Physical Examination Findings (Safety Outcome Measure)	Percentage of patients with clinically significant abnormal changes on physical examination at weeks 9, 17, 25 and 53 will be presented by treatment group. Clinically significant abnormal physical examination findings will be captured in medical history if prior to study drug treatment.	At baseline and weeks 9, 17, 25, and 53
Secondary	Changes In Blood Pressure (Safety Outcome Measure)	Percentage of patients with abnormal clinically significant changes in systolic and diastolic blood pressure will be presented by treatment group and visit.	Baseline to week 53
Secondary	Changes In Heart Rate (Safety Outcome Measure)	Percentage of patients with abnormal clinically significant changes in heart rate will be presented by treatment group and visit.	Baseline to week 53
Secondary	Changes In Temperature (Safety Outcome Measure)	Percentage of patients with abnormal clinically significant changes in body temperature will be presented by treatment group and visit.	Baseline to week 53
Secondary	Shift From Baseline In Selected Clinical Chemistry Laboratory Values At Follow-up (Safety Outcome Measure)	Percentage of patients with clinically significant abnormal values of potassium, sodium, magnesium, calcium (corrected) - per CTCAE5, urea and total protein - per investigator assessment will be presented by treatment group.	Baseline to week 53
Secondary	Shift From Baseline In Selected Hematology Laboratory Values At Follow-up (Safety Outcome Measure)	Percentage of patients with clinically significant abnormal changes in hemoglobin, erythrocytes, thrombocytes, leukocytes, absolute neutrophil count, basophils, eosinophils and monocytes will be presented by treatment group.	Baseline to week 53
Secondary	Changes From Baseline In Overall Electrocardiogram (ECG) Assessment At Follow-up (Safety Outcome Measure)	Percentage of patients with abnormal clinically significant changes on electrocardiogram (ECG) per central reviewer's assessment will be presented by treatment group.	Baseline and weeks 1, 9, 17, 25, 53 (131-I-1095 + enzalutamide treatment group); Baseline and week 53 (enzalutamide treatment group)
Secondary	Summary Of Concomitant Medications (Safety Outcome Measure)	Medications will be summarized by ATC4 class and generic term using number of participants and percentages by treatment group and overall.	Baseline to week 53 (concomitant medications); from week 54 up to 5 years (anti-cancer therapies only)