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
- High risk recurrent prostate cancer previously treated with radical prostatectomyMedDRA version: 21.0Level: PTClassification code 10036911Term: Prostate cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002957-46-CZ
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- 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. Previously treated with RP with lymph node dissection and post operative PSA at week 6 strictly <0.1 ng/mL.
5. Any pathologic stage at initial diagnosis: pTany, pNany, M0 (on CT/MRI/ 99mTc bone scan).
6. 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, estimated using the Memorial Sloan Kettering Cancer Center online calculator.
7. PSMA-PET must be performed at screening:
- Patients who are PSMA-PET-positive for loco-regional (pelvic) or distant (extra pelvic) lesions at screening, as confirmed by BICR, will be eligible to be randomized to either arm of the Interventional Cohort. The investigators and participants will be blinded to the location of the PSMA-PET lesions.
- Patients who are PSMA-PET-negative for any prostate cancer lesions (loco regional and/or distant) at screening, as confirmed by BICR, will be eligible for inclusion in the Observational Cohort.
8. No evidence of metastases on screening CT/MRI of the chest/abdomen/pelvis, Technetium 99m [99mTc] 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. Adequate organ function as defined by the following criteria:
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin less or equal than 2.5 X upper limit of normal (ULN); note that in participants with Gilbert’s syndrome, if total bilirubin is >2.5 X ULN, measure direct and indirect bilirubin. If direct bilirubin is =2.5 X ULN, the participant meets this eligibility criterion);
- 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. Be able to swallow whole study intervention tablets.
12. The participant must wear a condom when engaging in any sexual activity that allows for passage of ejaculate to another person while on study intervention, and for 3 months following the last dose of study intervention. Participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak.
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age ran
1. History of pelvic radiation for malignancy.
2. Persistent PSA post-RP (PSA =0.1 ng/mL at 6 weeks post-RP).
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 (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. Prior chemotherapy for prostate cancer.
11. 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.
12. 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
13. Chronic, active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction.
14. 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).
15. Treatment with drugs known to lower the seizure threshold within 4 weeks prior to randomization.
16. Known or suspected contraindications or hypersensitivity to apalutamide, LHRH agonist or any of the components of the formulations.
17. 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.
18. Plans to father a child while enrolled in this study or within 4 weeks after the last dose of study intervention.
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