Informations générales (source: ClinicalTrials.gov)
A Phase 4, Randomized, Open-label, Multicenter Efficacy and Safety Study of Standard Dose of Radium-223 Dichloride vs. Standard Doses of Novel Anti-hormonal Therapy (NAH) in Patients With Bone Dominant Metastatic Castration Resistant Prostate Cancer (mCRPC) Progressing on/After One Line of NAH
Interventional
Phase 4
Bayer (Voir sur ClinicalTrials)
novembre 2020
octobre 2026
02 septembre 2025
Researchers in this study want to compare how well drug radium-223 dichloride (Xofigo)
and new (novel) anti-hormonal (NAH) therapy work in participants with prostate gland
cancer which has spread to the bone and progressed on or after one line of NAH therapy.
Meanwhile researchers want to compare the safety of radium-223 dichloride and NAH
therapy. Radium-223 dichloride is known as a radioactive drug that is taken up by bones
after it is injected into the body. It works by giving off a type of radioactivity that
travels a very short distance and kills the tumor cells that have spread to the bone
without major effects to the healthy cells. It has been approved in many countries for
the treatment of patients with prostate cancer which has spread to the bone. The NAH
drugs used in this study will be either abiraterone acetate (Zytiga) (plus
prednisone/prednisolone) or enzalutamide (Xtandi). Both of them are standard approved
medications which are used in the treatment of advanced prostate cancer.
Participants in this study will receive either Radium-223 dichloride or a NAH therapy.
Radium-223 dichloride will be given as an infusion into one of the veins on Day 1 of each
4-week cycle for a total of up to 6 cycles. Oral NAH therapy will be given per the
standard approved dose once daily until the disease has progressed. Participants will
visit the hospital or clinic every 2 weeks for the first 6 cycles, and only on the first
day of each cycle from cycle 7 and onwards. Observation for each participant will last
for about 2 years in total. Blood and urine samples will be collected from the
participants and participants will be asked to complete questionnaires about the
well-being and the pain.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Karim FIZAZI | 15/04/2024 14:34:06 | Contacter | ||
Critères
Homme
- Participants who have histologically confirmed adenocarcinoma of the prostate.
- Participants with mCRPC progressing on/after one line of an approved NAH (eg.
abiraterone, enzalutamide, apalutamide, or darolutamide, after being treated for at
least 3 months) in an authorized prostate cancer indication.
- One prior taxane treatment regimen (at least 2 cycles) for metastatic prostate
cancer (mHSPC and mCRPC) or refusal or ineligibility of such a regimen.
- Prostate cancer progression documented by PSA according to the Prostate Cancer
Working Group 3 (PCWG3) criteria or radiological progression according to RECIST,
version 1.1.
- At least 2 bone metastases on bone scan within 4 weeks prior to randomization with
no current or history of lung, liver, other visceral, and / or brain metastasis.
- Symptomatic prostate cancer. A worst pain score (WPS) of at least 1 on the Brief
Pain Inventory-Short Form (BPI-SF) Question #3 (worst pain in last 24 hours). This
is to be assessed once during the Screening period.
- Maintenance of medical castration or surgical castration with testosterone less than
50 ng/dL (1.7 nmol/L). If the participant is being treated with luteinizing hormone
releasing hormone (LHRH) agonists or antagonists (participant who has not undergone
orchiectomy), this therapy must have been initiated at least 4 weeks prior to
randomization and must be continued throughout the study.
- Participants must be on a BHA treatment, such as bisphosphonates or denosumab
treatment unless such treatment is contraindicated or not recommended per
investigator's judgement and inclusion is agreed to by the medical monitor.
- Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
- Life expectancy ≥ 6 months.
- Able to swallow abiraterone and prednisone/prednisolone or enzalutamide as whole
tablets/capsules.
- Laboratory requirements:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- Platelet count ≥ 100 x 10^9/L
- Hemoglobin (Hb) ≥ 9.0 g/dL (90 g/L; 5.6 mmol/L)
- Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN) (except
for participants with documented Gilbert's disease)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
- Creatinine ≤ 1.5 x ULN or estimated glomerular filtration rate (eGFR) ≥ 30
mL/min/1.73 m^2 as calculated using the Cockcroft-Gault equation
- International normalized ratio (INR) of prothrombin time (PT; PT-INR) and
partial thromboplastin time (PTT) ≤ 1.5 times the ULN. Participants treated
with warfarin or heparin will be allowed to participate in the study if no
underlying abnormality in coagulation parameters exists per prior history;
weekly evaluation of PT-INR / PTT will be required until stability is achieved
(as defined by local standard of care and based on pre-study PT-INR / PTT
values)
- Serum albumin > 30 g/L
- Serum potassium ≥ 3.5 mmol/L
- Capable of giving signed informed consent
Exclusion Criteria:
- Active infection or other medical condition that would make prednisone /
prednisolone (corticosteroid) use contraindicated.
- Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg
prednisone / prednisolone equivalent daily for more than 2 months.
- Pathological finding consistent with tumors with predominant neuroendocrine features
or small cell carcinoma of the prostate.
- History of osteoporotic fracture
- History of visceral metastasis, or presence of visceral metastasis detected by
screening imaging examinations.
- History of or known brain metastasis.
- Malignant lymphadenopathy exceeding 3 cm in short-axis diameter.
- Other malignancy treated within the last 3 years (except non-melanoma skin cancer or
low-grade superficial bladder cancer)
- Imminent spinal cord compression based on clinical findings and / or magnetic
resonance imaging (MRI). Participants with history of spinal cord compression should
have completely recovered.
- Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood
pressure ≥ 95 mmHg). Participants with a history of hypertension are allowed
provided blood pressure is controlled by anti-hypertensive treatment.
- Active or symptomatic viral hepatitis
- History of pituitary or adrenal dysfunction
- Any other serious illness or medical condition such as, but not limited to:
- Any infection ≥ National Cancer Institute Common Terminology Criteria for
Adverse Events (NCI-CTCAE) version 5.0 Grade 2
- Clinically significant heart disease as evidenced by myocardial infarction, or
arterial thrombotic events in the past 6 months, severe or unstable angina, or
New York Heart Association (NYHA) Class II to IV heart disease or cardiac
ejection fraction measurement of <50% at baseline
- Current clinical evidence of any uncontrolled cardiac arrhythmia
- Crohn's disease or ulcerative colitis
- Bone marrow dysplasia
- Moderate and severe hepatic impairment (Child-Pugh Classes B and C)
- Unmanageable fecal incontinence.
- Any condition, which in the opinion of the investigator would preclude participation
in this trial (eg, history of seizure).
- Hypersensitivity to the active substances or to any excipients of radium-223
dichloride, or abiraterone acetate or enzalutamide.
- Prior therapeutic systemic radiation with any radiopharmaceutical medication for the
treatment of prostate cancer, including but not limited to lutetium-177,
strontium-89, samarium-153, iodine-131, rhenium-186, rhenium-188, or radium-223.
Radiopharmaceutical compounds used for diagnosis purposes only are allowed.
- Prior hemibody external radiotherapy is excluded. Participants who received other
types of prior external radiotherapy are allowed provided that the bone marrow
function is assessed and meets the protocol requirements for Hb, ANC, and platelet
count.
- Blood transfusion or erythropoietin stimulating agents 4 weeks prior to Screening
and during the whole Screening period before randomization.
- Excessive intake of biotin above the recommended daily dose of 30 μg. Biotin is
found in multivitamins, including prenatal multivitamins, biotin supplements, and
dietary supplements for hair, skin, and nail growth at levels that may interfere
with laboratory tests.
- Prior administration of an investigational therapeutic for CRPC.
- Previous (within the last 4 weeks of randomization) or concurrent participation in
any interventional clinical study with investigational study drug administration.