Radium RA 223 dichloride for Metastatic castration-resistant prostate cancer

Stratification factors

• Prior docetaxel for castration-sensitive disease (Yes or No)
• Visceral disease (presence or absence)

Inclusion criteria

• {"criterion_text":"- Willing and able to provide, or have a legally authorized representative provide, written informed consent (ICF) and HIPAA authorization for the release of personal health information. A signed ICF must be obtained before screening procedures are performed. NOTE: HIPAA authorization may be either included in the ICF or obtained separately\n- Males 18 years of age and abov\n- Histological or cytological proof of prostate cancer\n- Documented progressive mCRPC based on at least one of the following criteria: a) PSA progression defined as a minimum of 2 rising PSA levels with a minimum of a 1 week interval between each determination. A minimum PSA of 1.0 ng/mL is required for study entry. b) Soft-tissue progression defined as an increase ≥ 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions. c) Progression of bone disease (evaluable disease) by two or more new bone lesions by bone scan\n- Two or more bone lesions defined by nuclear bone scan\n- ECOG of 0 or 1 (Appendix A: Performance Status Criteria)\n- Normal organ function with acceptable initial laboratory values within 14 days of randomization\n- Subjects must agree to use a medically acceptable method of birth control (e.g., spermicide in conjunction with a barrier such as a condom) or sexual abstinence for the duration of the study, including 6 months after the last dose of study drug. Sperm donation is prohibited during the study and for 6 months after the last dose of study drug. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent\n- Serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH analogue (agonist or antagonist) if they have not undergone orchiectomy\n- All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1 or less\n- Willing and able to comply with the protocol, including follow-up visits and examinations"}

Exclusion criteria

• {"criterion_text":"- Received any other investigational therapeutic agents or other anticancer therapies within 2 weeks or 5 half-lives, whichever is shorter, prior to randomization. Note: If this requirement to have a washout of 2 weeks or 5 half-lives prior to randomization causes potential treatment delay due to Radium-223 importation timelines, the PCCTC must be contacted to request approval to randomize the subject prior to the completion of the washout. Requests for early randomization must be accompanied by written assurance by the site that the washout will be completed prior to treatment start.\n- Received external beam radiotherapy (EBRT) within the 2 weeks prior to randomization. Note: If prolonging randomization to complete EBRT washout causes potential treatment delay due to Radium-223 importation timelines, the PCCTC must be contacted to request approval to randomize the subject prior to the completion of the washout. Requests for early randomization must be accompanied by written assurance by the site that the washout will be completed prior to treatment start\n- Has an immediate need for EBRT.\n- Has received any other systemic investigational or anti-cancer radiopharmaceutical in the past\n- Has received any prostate cancer directed chemotherapy in the castration resistant setting\n- Has received > 6 prior doses of docetaxel in the castration sensitive setting. Subjects who have received up to 6 prior doses of docetaxel in the castration sensitive setting are permitted if they have not experienced disease progression within 36 weeks of last treatment with docetaxel\n- Has received four or more systemic anticancer regimens for mCRPC\n- Has known Grade ≥3 non-hematological docetaxel-related toxicities or docetaxel toxicity related dose interruption or discontinuation\n- Has received blood transfusions or growth factors within the last 4 weeks prior to randomization.\n- Symptomatic nodal disease (i.e., scrotal, penile, or leg edema)\n- Has visceral metastases with > 3 lung and/or liver metastases or individual lesion >2 cm, as assessed by CT scan or MRI of the chest/abdomen/pelvis within the last 8 weeks prior to randomization\n- Symptomatic loco-regional disease that causes ongoing Grade 3 or Grade 4 urinary or rectal symptoms\n- Subjects with a second malignancy with a risk of recurrence >30% within the next 3 years. Non-melanoma skin cancers, non-invasive bladder cancers, and other in-situ or non-invasive malignancies are permitted while on study\n- Has imminent or established cord compression based on clinical findings and/or MRI\n- Known bone marrow dysplasia\n- Has received any of the following in the 4 weeks prior to randomization: 5-alphareductase inhibitors, natural hormonally active foods (e.g., phytoestrogens) or other food supplements known to alter PSA in humans\n- Is receiving ongoing treatment with herbal medications that are known in humans to alter PSA or the natural history of prostate cancer. Subjects must discontinue any such herbal medications prior to the first dose of study drug\n- Any other serious illness or medical condition that would, in the opinion of the Investigator, make this protocol unreasonably hazardous, including but not limited to: • Uncontrolled infection • NYHA III or IV heart failure • Crohn’s disease or those with ulcerative colitis who have not undergone a colectomy • Known active infection with HIV, Hepatitis B or Hepatitis C"}

Primary endpoints

• {"endpoint_text":"- The OS comparison between treatments will be evaluated at each interim analysis and the final analysis using the stratified logrank test. The stratification factors are: 1. Prior docetaxel for castration-sensitive disease (Yes or No) 2. Visceral disease (presence or absence)","definition_or_measurement_approach":"Overall survival (OS) comparison evaluated at each interim analysis and at final analysis using a stratified logrank test. Stratification factors: prior docetaxel for castration-sensitive disease (Yes/No) and presence/absence of visceral disease."}

Secondary endpoints

• {"endpoint_text":"- Time to event endpoints will be analyzed using a stratified logrank test with the same stratification factors. Kaplan-Meier estimates of SSE-free survival and radiographic PFS will be computed. The cumulative incidence function will be used to compute probabilities for the time to first skeletal related event and the time to ALP progression. All time to event probability estimates will be calculated within treatment.","definition_or_measurement_approach":"Time-to-event endpoints analyzed with stratified logrank test (same stratification factors). Kaplan-Meier estimates for SSE-free survival and radiographic PFS; cumulative incidence function for time to first skeletal related event and time to ALP progression; probabilities calculated within treatment arms."}
• {"endpoint_text":"- Total ALP response will be compared between the treatment groups using a CMH test adjusting for the randomization strata","definition_or_measurement_approach":"Total alkaline phosphatase (ALP) response comparison between groups using a Cochran-Mantel-Haenszel (CMH) test adjusted for randomization strata."}
• {"endpoint_text":"- Time to maximum % post-therapy decrease in PSA will be summarized using descriptive statistics","definition_or_measurement_approach":"Time to maximum percent decrease in PSA post-therapy summarized using descriptive statistics."}
• {"endpoint_text":"- Maximum % decrease in PSA will be summarized using descriptive statistics (e.g., mean, standard deviation, median, minimum, and maximum)","definition_or_measurement_approach":"Maximum percentage decrease in PSA summarized with descriptive statistics (mean, SD, median, min, max)."}
• {"endpoint_text":"- Longitudinal kernel smoothing methods will be used to estimate the PSA, bone marker, BSI, CTC, and ctDNA trajectories over time. Joint modeling will used to evaluate these trajectories with respect to OS","definition_or_measurement_approach":"Longitudinal kernel smoothing to estimate biomarker (PSA, bone marker, BSI, CTC, ctDNA) trajectories; joint modelling to evaluate relationships with overall survival."}
• {"endpoint_text":"- PROs will include scores from the QOL questionnaires: FACT-P, BPI, and BFI. The QOLs will be administered at baseline, week 19, Safety Follow Up, and Follow Up visits every 3 months for 1 year from last dose of either study drug. The score-specific area under the curve (with respect to time) will be derived for each subject and these area-under-curve (AUCs) will be compared between treatments.","definition_or_measurement_approach":"Patient-reported outcomes: FACT-P, BPI, BFI administered at baseline, week 19, safety follow-up and every 3 months for 1 year after last dose; score-specific AUC derived per subject and compared between treatments."}
• {"endpoint_text":"- The number and percentage of febrile neutropenia in subjects treated with docetaxel plus Radium-223","definition_or_measurement_approach":"Count and percentage of subjects experiencing febrile neutropenia in the docetaxel + Radium-223 arm."}
• {"endpoint_text":"- The percentage of treatment discontinuation in subjects who are on their fourth line of therapy will be calculated by treatment arm and total","definition_or_measurement_approach":"Percentage of treatment discontinuation among subjects on fourth-line therapy calculated per treatment arm and overall."}

Netherlands

Earliest CTIS Part Ii Submission Date

25-09-2024

Latest Decision Or Authorization Date

04-12-2025

Processing Time Days

435

Number Of Sites

13

Number Of Participants

250

Spain

Earliest CTIS Part Ii Submission Date

25-09-2024

Latest Decision Or Authorization Date

21-07-2025

Processing Time Days

299

Number Of Sites

11

Number Of Participants

35

Primary sponsor

Full Name

Memorial Sloan Kettering Cancer Center

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

United States

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Prostate Cancer Clinical Trials Consortium","duties_or_roles":"sponsorDuties code 5","organisation_type":"Health care"}
• {"country":"United States","full_name":"Cenetron Diagnostics Ltd.","duties_or_roles":"sponsorDuties code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Siron B.V.","duties_or_roles":"sponsorDuties code 1","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"AG Mednet Inc.","duties_or_roles":"Image processing facility","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"EPIC Sciences","duties_or_roles":"sponsorDuties code 4","organisation_type":"Health care"}
• {"country":"Italy","full_name":"Menarini-Silicon Biosystems S.p.A.","duties_or_roles":"sponsorDuties code 4","organisation_type":"Health care"}
• {"country":"United States","full_name":"Progenics Pharmaceuticals","duties_or_roles":"Image processing facility","organisation_type":"Health care"}