Darolutamide With Radium-223 or Placebo and the Effect on Radiological Progression-Free Survival for Patients With mCSPC

NCT05771896 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: 00019_CARE
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to compare the combination of Darolutamide with Radium-223 or placebo and the effects on radiological progression-free survival for patients with Metastatic Castration-Sensitive Prostrate Cancer (mCSPC) The main questions it aims to answer are:

• Radiological progression-free survival (rPFS) in mCSPC
• Overall Survival (OS)
• Symptomatic skeletal event-free survival (SSE-FS)
• Initiation of subsequent antineoplastic therapy
• Safety Participants will have visits at baseline, treatment is once a month for up to 6 months, and long term follow up will continue until the participant dies, withdraws consent, and/or study is terminated.

Conditions

Metastatic Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Radiological progression-free survival (rPFS) in mCSPC patients

  The primary objective of this study is to compare the radiological progression-free survival (rPFS) in mCSPC patients treated with darolutamide plus radium-223 versus darolutamide plus placebo. The primary endpoint is radiological progression-free survival rPFS, defined as time to first occurrence of 99mTc MDP+ bone scan progression per PCWG3 criteria, and/or soft tissue progression by CT/MRI per PCWG3 modifications to RECIST 1.1 criteria, or death from any cause. Randomization will be stratified by ECOG performance status 0 vs 1-2, and metastatic disease status, specifically low volume (\<4 bone lesions) versus high volume (≥4 bone lesions).

  First occurrence bone scan progression and/or soft tissue progression per #RECIST 1.1 criteria, participant dies, withdraws consent and/or study is terminated, whichever comes first.

Secondary Outcomes (3)

• Overall Survival (OS) & Symptomatic Skeletal Event-Free Survival (SSE-FS)

  Randomization until death.

• Initiation of Subsequent Antineoplastic Therapy

  Randomization to initiation of first subsequent antineoplastic therapy for prostrate cancer.

• Safety of the combination of radium-223 and Darolutamide

  First treatment dose until last dose + 30 Days

Study Arms (2)

Darolutamide with Radium-223

EXPERIMENTAL

Darolutamide: Dosage:600mg Route: By mouth (PO) Frequency: Twice a day, throughout the duration of the study Radium-223: Dosage: 55 kBq/kg body weight or 1.49 microcurie/kg body weight Route: IV Frequency: Every 28+/-7 days, a maximum of 6 cycles

Drug: Darolutamide; Drug: Radium-223

Darolutamide with Placebo

PLACEBO COMPARATOR

Darolutamide: Dosage:600mg Route: By mouth (PO) Frequency: Twice a day, throughout the duration of the study Placebo: Dosage: 55 kBq/kg body weight or 1.49 microcurie/kg body weight Route: IV Frequency: Every 28+/-7 days, a maximum of 6 cycles

Drug: Darolutamide

Interventions

Darolutamide DRUG

Participants will continue treatment with darolutamide until radiological progression, withdrawal, death, termination, or study completion. The maximum time for darolutamide dose interruption period is 28 consecutive days beyond scheduled dose (\>56 days between cycles). Any participant requiring dose interruption \>28 consecutive days beyond the scheduled dose may restart treatment with darolutamide if clinical benefit is anticipated and after discussion with and approval from the study Medical Monitor. Until primary endpoint is reached, participants are not allowed to switch ARPI (Abiraterone, Apalutamide or Enzalutamide) during the study. Switching to other ARPI following radiographic progression should be considered a subsequent life prolonging therapy and documented accordingly.

Also known as: Nubeqa

Darolutamide with Placebo; Darolutamide with Radium-223

Radium-223 DRUG

Radium-223 should be given for 6 cycles, administered IV on Day 1 of each cycle or until radiological progression, withdrawal, death, termination, or study completion. The placebo will be administered in precisely the same fashion as the active drug. Subsequent cycles 2-6 should be scheduled to occur every 28 ± 7 days following the previous cycle, but dosing may be delayed up to 28 days per cycle (maximum 56 days between cycles). Any participant requiring dose interruption \>28 consecutive days (\>56 days between cycles) may restart treatment with radium-223/placebo if clinical benefit is anticipated and after discussion with the Medical Monitor. Participants will continue with darolutamide irrespective of Radium-223 administration. Upon radiological progression, further treatments are decided by the site investigator according to standard local practice.

Also known as: Xofigo

Darolutamide with Radium-223

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Males with Metastatic Castration-Sensitive Prostrate Cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is able and willing to provide informed consent.
• Metastatic castration-sensitive prostate cancer (mCSPC) at screening with histologically or cytologically confirmed diagnosis of prostate adenocarcinoma.
• Men ≥ 18 years.
• ECOG performance status of 0, 1 or 2 at screening.
• Metastatic to bone with ≥ 2 bone metastases (area of increased uptake on 99mTc methylene diphosphonate bone scan); equivocal lesions on the bone scan must be confirmed by standard X-ray, CT, or MRI.
• Ongoing ADT by Investigator's choice with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or bilateral orchiectomy for less than 120 days prior to randomization. ADT treatment should be on a stable dose without interruptions of at least 4 weeks prior to first dose of blinded IP.
• On bone health agents with at least one dose of BHA prior to first dose of blinded IP.
• Adequate bone marrow and organ function as defined by:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L (participant must not have received any growth factor within 4 weeks or a blood transfusion within 7 days of the hematology laboratory sample obtained at Screening)
• Serum creatinine ≤2 x upper limit of normal ULN
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 1.5 x upper limit of normal (ULN)
• Total bilirubin \< 1.5 x ULN, unless the participant a diagnosis of Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin; in participants with Gilbert's, the total bilirubin should be \< 3 x ULN and the elevation should be seen in the unconjugated or indirect bilirubin measurement)
• Albumin ≥ 2.5 g/dL

You may not qualify if:

• Pathological finding consistent with small cell carcinoma of the prostate.
• Prior treatment for mCSPC \[excluding ADT ≤120 days and first-generation ARI (bicalutamide, nilutamide or flutamide) for ≤120 days when initiating ADT\], with the exception of Metastases Directed Therapy (MDT) with EBRT/SBRT (at least 2 bone metastases must be untreated). Prior treatment for localized prostate cancer is allowed (all treatments must have been completed ≥ 1 year prior to randomization)
• Treatment for mCSPC with ADT starting \>120 days prior to randomization.
• Treatment for mCSPC with first generation ARI (bicalutamide, nilutamide or flutamide) starting \>120 days prior to randomization.
• Prior hemi-body or whole-body external radiotherapy.
• a. Other types of prior external radiotherapy and brachytherapies are allowed, if more than 28 days prior to randomization.
• Prior therapy with radionuclides (e.g., including but not limited to radium-223, strontium-89, samarium-153), including prior therapy with investigational radionuclides (e.g., including but not limited to iodine-131, rhenium-186, rhenium- 188, thorium- 277, actinium-225 and lutetium-177).
• Prior treatment with:
• Second-generation androgen receptor (AR) inhibitors such as enzalutamide, darolutamide, apalutamide or other investigational AR inhibitors.
• Cytochrome P 17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as antineoplastic treatment for prostate cancer.
• Chemotherapy including docetaxel or immunotherapy for prostate cancer.
• Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days prior to randomization.
• Current involvement in any drug or device trial involving investigational agent or medical device within the last 28 days prior to randomization.
• Any prior investigational agent for nmCSPC/mCSPC.
• Known hypersensitivity to compounds related to darolutamide, or radium-223, or to CT and/or MRI contrast media.

Sponsors & Collaborators

• GenesisCare USA: lead
• Bayer: collaborator

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

darolutamide; Radium-223; radium Ra 223 dichloride

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2023
• First Posted: March 16, 2023
• Study Start: September 1, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): April 1, 2029
• Last Updated: September 14, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share