The Combination Therapy With Ra-223 and Enzalutamide (CORE-OCU)

The Study of Combination Therapy With Radium-223 and Enzalutamide in Osaka City University

This study is to evaluate preliminary efficacy of Ra-223 in combination with Enzalutamide in progressive CRPC patients with bone metastasis

Study Overview

• Status: Active, not recruiting
• Conditions: Bone Metastases; Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Ra-223 in combination with enzalutamide

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 545-8585
    • Osaka City University Graduate School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Patients diagnosed as CRPC
2. Surgical or those who will be treated with luteinizing hormone-releasing hormone (LHRH) agonists throughout the study period,
3. Patients who had >30% of PSA response to enzalutamide prior to enrollment,
4. Interval between PSA progression and enrollment is up to 3 months,
5. With bone metastases (≥ 2 hot spots) on bone scintigraphy within previous 24 weeks,
6. No intention to use anti-cancer chemotherapy within the next 6 months,
7. Eastern Cooperative Oncology Group performance status (ECOG-PS): 0-1,
8. Life expectancy ≥ 6 months,

9. Laboratory requirements within 30 days before enrollment:

   • Absolute neutrophil count (ANC) ≥ 1.5 x 10e9/L,
   • Platelet count ≥ 100 x 10e9/L,
   • Hemoglobin ≥ 10.0 g/dL,
   • Total bilirubin level ≤1.5 institutional upper limit of normal (ULN),
   • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 ULN,
   • Creatinine ≤ 1.5ULN, and estimated glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2,
10. Age ≥ 20,
11. Ability to understand and the willingness to sign a written informed consent (IC).

Exclusion Criteria:

1. Prior chemotherapy or planned treatment with chemotherapy,
2. PSA progression within 3 months after initiation of enzalutamide
3. Prior treatment with corticosteroids, estramustine or abiraterone acetate,
4. Any systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bone metastases,
5. Had history of gastrointestinal bleeding or ulcer within 3 months prior to study entry,
6. History of visceral metastasis, or presence of visceral metastasis detected by screening imaging examinations,
7. History of or known brain metastasis,
8. Malignant lymphadenopathy ≧1.5 cm in short axis,
9. Imminent or established spinal cord compression based on clinical findings and/or MRI (Magnetic Resonance Imaging),
10. Any other serious illness or medical condition
11. Substance abuse, medical, psychological, or social conditions that might interfere with the subject's participation in the study or evaluation of the study Results
12. Those who judged to be inappropriate by the principal investigator or co-investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Ra-223 + Enzalutamide	Drug: Ra-223 in combination with enzalutamide; Ra-223 (55 kBq/kg i.v.) 6 injections at 4 weeks interval in combination with enzalutamide 160 mg per a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Alkaline phosphatase (ALP)	Percentage of change from baseline to 6 months (or earlier for those who discontinue study therapy)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of Radium-223 therapy	Proportion of patients who complete 6 times injections of radium-223	6 months
Evaluation for bone metastasis by 18F-NaF-PET	Fractional decline of intensity of tracer uptake measured by SUVmax on 18F-NaF-PET at 1, 3, 6 months.	1, 3, 6 months
Evaluation for bone metastasis by bone scintigraphy	The change of Bone Scan Index (BSI) by bone scintigraphy at 1, 3, 6 months.	1, 3, 6 months
Overall Survival Rate	Overall Survival (OS) is defined as the time from the registration to death due to any cause, or censored at date last known alive.	3 years
Time to occurrence of Symptomatic Skeletal-related Events (SSEs)	Time to occurrence of SSEs are defined asthe time from registration to the date of the occurrence of SSEs (symptomatic fracture, surgery or radiation to bone, or spinal cord compression).	1 year
Time to occurrence of visceral metastasis	Time to occurrence of visceral metastasis was defined as the time from registration to the date of the occurrence of a visceral metastasis for each patient.	1 year
Time to initiation of cytotoxic chemotherapy	The time to initiation of cytotoxic chemotherapy is defined as the time from registration to the date of initiation of cytotoxic chemotherapy.	1 year
Changes in Prostate Specific Antigen (PSA)	Percent change in prostate-specific antigen (PSA) from baseline at 6 months.	6 months
Changes From Baseline for Brief Pain Inventory (BPI)	The change for the BPI-SF (Brief Pain Inventory-Short Form) score was calculated.	6 months
Changes From Baseline for Functional Assessment of Cancer Therapy - Prostate (FACT-P)	The change for the FACT-P TOI domain (physical and social well-being and prostate specific score) was calculated.	6 months
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	Number of participants with adverse events as a measure of safety and tolerability.	6 months

Collaborators and Investigators

• Sponsor: Taro Iguchi, MD, PHD
• Collaborators: Bayer Yakuhin, Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 27, 2017
• Primary Completion (ANTICIPATED): October 30, 2021
• Study Completion (ANTICIPATED): March 31, 2022

Study Registration Dates

• First Submitted: August 28, 2017
• First Submitted That Met QC Criteria: October 3, 2017
• First Posted (ACTUAL): October 9, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 9, 2021
• Last Update Submitted That Met QC Criteria: September 8, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: bone metastasis; castration-resistant prostate cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplastic Processes; Prostatic Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: CORE-OCU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No