A Study Comparing ARB With Radium-223 vs ARB Therapy With Placebo and the Effect Upon Survival for mCRPC Patients

Stopped early · Phase 3 · Has a placebo group

Conditions studied: Metastatic Castration-resistant Prostate Cancer

In brief

This is a randomized, multi-center, double-blind, Phase III study of radium-223 plus enzalutamide or darolutamide compared to enzalutamide or darolutamide treatment plus placebo.

Key facts

Study ID

NCT04237584

Run by

MANA RBM

People needed

23

Starts

2020-06-30

Expected to finish

2022-03-07

Last updated by the study team

2022-10-07

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

You may qualify if…

• Able and willing to provide informed consent.
• Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma.
• Men ≥ 18 years.
• ECOG performance status of 0 or 1 at screening.
• Metastatic to bone with ≥ 2 bone metastases (area of increased uptake on 99mTc bone scan); equivocal lesions on the bone scan must be confirmed by standard X-ray, CT, or MRI.
• Patients must have progressive metastatic castration-resistant prostate cancer (mCRPC) at screening and on androgen deprivation therapy (ADT) as evidenced by either:
• For patients who manifest disease progression solely as a rising prostate-specific antigen (PSA) level - documentation of a sequence of two rising PSA values at a minimum of 1-week apart with the Screening value ≥1 ng/ml (see Appendix D);
• For patients with disease progression manifested in the bone, irrespective of progression by rising PSA - defined by the appearance of 2 or more new skeletal lesions demonstrated by 99Tc bone imaging. Ambiguous results should be confirmed by other imaging modalities than bone scan and x-ray (e.g.: CT-scan or MRI).
• For patients with disease progression manifested at nodal sites, irrespective of progression by rising PSA - progression defined per RECIST 1.1.
• Ongoing ADT with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or bilateral orchiectomy.
• Use of bone health agents (denosumab or zoledronic acid or other bisphosphonates) starting any time prior to R1 unless contraindicated or considered not in the best interest of the patient. A waiver must be approved by the medical monitor if bone health agents cannot be used. Bone health agents should be continued throughout both RT1 and RT2 treatment periods.
• Adequate bone marrow and organ function as defined by:
• Hemoglobin ≥ 10.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Serum creatinine ≤ 1.95 mg/dL
• Estimated creatinine clearance >/= 30 mL/min by Cockroft-Gault calculation
• Alanine aminotransferase (ALT) ≤ 175 U/L
• Aspartate aminotransferase (AST) ≤ 100 U/L
• Total bilirubin ≤ 1.8 mg/dL (unless the patient a diagnosis of Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin; in patients with Gilbert's, the total bilirubin should be less than 6 mg/dL if patient has Gilbert's and the elevation should be seen in the unconjugated or indirect bilirubin measurement)
• LDH ≤ 224 U/L at screening.
• Albumin ≥ 2.5 g/dL
• Fertile male patients, defined as all males physiologically capable of conceiving offspring with female partners of child-bearing potential, must be willing to use condoms plus spermicidal agent during the study treatment period and for 6 months after the last dose of study drug, and not father a child or donate sperm during this period.
• The treating site investigator deems RT1 (Enzalutamide or Darolutamide) treatment safe and feasible.
• Subjects must meet the remaining inclusion criteria in order to be qualified for the second randomization (R2). Only subjects that complete the initial 12 weeks of run-in RT1 should be evaluated. Prior inclusion criteria do not need to be re-evaluated:

You may not qualify if…

• Pathological finding consistent with small cell carcinoma of the prostate.
• Prior chemotherapy for CRPC. Prior docetaxel for hormone-sensitive disease is permitted under the following conditions: started within 3 months of ADT initiation, given for a maximum of 6 cycles and progression occurred > 6 months after the last dose of docetaxel.
• Prior treatment for mCRPC or CRPC. However, the following therapies are permitted and not exclusionary: Sipuleucel-T, 5-alpha-reductase inhibitors, estrogens, or older antiandrogens (such as flutamide, bicalutamide, or nilutamide).
• Prior treatment for more than 2 months with CYP17 inhibitors (e.g. abiraterone or orteronel).
• Prior treatment for more than 2 months with agents inhibiting androgen receptor signaling (e.g. enzalutamide, apalutamide, or darolutamide).
• Prior hemibody or whole-body external radiotherapy. Other types of prior external radiotherapy and brachytherapies are allowed.
• Prior therapy with radionuclides (e.g., radium-223, strontium-89, samarium-153, rhenium-186, rhenium-188, actinium-225 and lutetium-177).
• Current involvement in any drug or device trial involving investigational agent or medical device within the last 28 days prior to R1.
• In general, any prior investigational agent for nmCRPC/mCRPC; however, may be reviewed by medical monitor/PIs for waiver consideration, on a case-by-case basis.
• Hypersensitivity to compounds related to enzalutamide, darolutamide, or Ra-223.
• A blood transfusion ≤ 28 days prior to R1.
• Major surgical procedures ≤ 28 days or minor surgical procedures ≤7 days prior to R1. No waiting period is required following port-a-cath placement.
• Patients with visceral metastases, clinical evidence of central nervous system metastases, or leptomeningeal tumor spread as demonstrated via CT/MRI of chest, abdomen, pelvis, and CNS (if needed). CT/MRI of the CNS only performed if suspicion of CNS metastases or leptomeningeal tumor spread. Nodules < 1 cm alone will not be considered visceral metastases. Renal masses < 3 cm will not be considered exclusionary.
• Serious active infection at the time of screening or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
• Presence of other active cancers, or history of treatment for invasive cancer ≤2 years of R1. Patients with Stage I/II cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) and superficial bladder cancer are eligible, as are patients with history of non-melanoma skin cancer.
• Any other serious or unstable illness, or medical, social, or psychological condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results.

Where it is running

• Research Site — Myrtle Beach, South Carolina, United States

Full record on ClinicalTrials.gov

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