A research study to assess the efficacy and safety of apalutamide in the treatment of high-risk Hormone-Sensitive Prostate Cancer assessed by an imaging scan.
- Conditions
- Therapeutic area: Diseases [C] - Cancer [C04]High risk recurrent prostate cancer previously treated with radical prostatectomy
- Registration Number
- EUCTR2019-002957-46-IT
- Lead Sponsor
- JANSSEN CILAG INTERNATIONAL NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 412
1. Male, 18 years of age or older (or the legal age of consent in the country in which the study is taking place).
2 Signed an Informed Consent Form (ICF) indicating that the participant understands the purpose of, and procedures required for the study and is willing to participate in the study; participants must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
3. Histologically confirmed adenocarcinoma of the prostate.
4. Criterion changed per Amendment 1.
4.1 Previously treated with radical prostatectomy with lymph node dissection and first
post-operative PSA measurement of <0.1 ng/mL between Week 6 and Week 13.
5. Any pathologic stage at initial diagnosis: pTany, pNany, M0 (on CT/MRI and 99mTc bone scan).
6. Criterion changed per Amendment 1.
6.1 Biochemically recurrent prostate cancer after RP with a high risk of developing metastasis defined as
- pathological Gleason score =8 at diagnosis or time of surgery, OR
- PSADT =12 months at the time of screening using at least 3 consecutive values =0.1 ng/mL, from time of BCR, estimated using the Memorial Sloan Kettering Cancer Center online calculator.
7. Criterion changed per Amendment 1.
7.1 PSMA-PET must be performed at screening:
- Patients who are PSMA-PET-positive for at least one loco-regional (pelvic) lesion with or without distant (extra pelvic) lesions at screening, as determined by BICR, will be eligible to be randomized to either arm of the Interventional Cohort. The investigators will be blinded to the location of the PSMA-PET lesions after randomization.
- Patients who are PSMA-PET-negative for any prostate cancer lesions (ie, no loco regional lesion and no distant lesions) at screening, as determined by BICR, will be eligible for inclusion in the Observational Cohort.
8. Criterion changed per Amendment 1.
8.1 No evidence of metastases on screening CT/MRI of the chest/abdomen/pelvis, 99m Tc whole-body bone scan. Participants with a single bone lesion on 99mTc whole-body bone scan should have confirmatory imaging by CT or MRI; if the confirmatory scan confirms the bone lesion, the patient should be excluded from the study.
9. Eastern Cooperative Oncology Group Performance Status Grade 0 or 1.
10. Criterion changed per Amendment 1.
10.1 Adequate organ function as defined by the following criteria:
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 X upper limit of normal (ULN) and total bilirubin =1.5 x ULN.
- Serum creatinine <1.8 mg/dL.
- Platelets =75,000/µL, without transfusion and/or growth factors within 1 month prior to randomization.
- Hemoglobin =10.0 g/dL (6.21 mmol/L), without transfusion and/or growth factors within 1 month prior to randomization.
11. Criterion changed per Amendment 1.
11.1 Be able to swallow whole the study drug tablets or follow the instructions for admixing with apple sauce.
12. Criterion changed per Amendment 1.
12.1 If the participant engages in sexual activity with a woman of childbearing potential, a condom must be used together with another highly effective method of contraception during the Treatment Period and for 3 months after the last dose of study intervention.
13. The participant must agree not to donate sperm for the purpose of reproduction during the Treatment Phase and for a minimum 3 months after receiving the last dose of study intervention.
14. Criterion added per Amendment 1.
Participants receiving bone-loss prevention treatment with bone-sparing agents
1. History of pelvic radiation for malignancy.
2. Criterion deleted per Amendment 1.
3. Previous treatment with ADT for prostate cancer.
4. Previously treated for BCR prostate cancer.
5. Prior treatment with a CYP17 inhibitor (eg, oral ketoconazole, orteronel, abiraterone acetate, galeterone) or any AR antagonist including bicalutamide, flutamide, nilutamide, apalutamide, enzalutamide or darolutamide and any other medications that may lower androgen levels (eg. estrogens, progestins, aminoglutethimide, etc.), including bilateral orchiectomy.
6. Pathological finding consistent with small cell, or neuroendocrine carcinoma of the prostate.
7. Any of the following within 6 months prior to first dose of study intervention: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary
8. Use of 5-alpha-reductase inhibitor =4 weeks prior to randomization.
9. Use of investigational agent =4 weeks prior to randomization.
10. Not applicable; criterion numbering omitted from initial protocol in error.
11. Prior chemotherapy for prostate cancer.
12. Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are:
- Non-muscle invasive bladder cancer.
- Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured.
- Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and considered to have a very low risk of recurrence.
- Malignancy that is considered cured with minimal risk of recurrence.
13. Human immunodeficiency virus-positive participants with 1 or more of the following:
- Not receiving highly active antiretroviral therapy
- Had a change in antiretroviral therapy within 6 months of the start of screening
- Receiving antiretroviral therapy that may interfere with study intervention (consult Sponsor for review of medication prior to enrollment)
- CD4 count <350 at screening
- AIDS-defining opportunistic infection within 6 months of start of screening
14. Chronic, active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction.
15. History of seizure or any condition that may predispose to seizure (including, but not limited to, prior stroke, transient ischemic attack, or loss of consciousness =1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect).
16. Treatment with drugs known to lower the seizure threshold within 4 weeks prior to randomization.
17. Known or suspected contraindications or hypersensitivity to apalutamide, LHRH agonist or any of the components of the formulations.
18. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant.
Plans to father a child while enrolled in this study or within 4 weeks after the last dose of study intervention.
19. Criterion deleted per Amendment 1.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method