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-AT
- 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. Person, 18 years of age or older (or the legal age of consent in the jurisdiction 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.
4.1 Criterion changed per Amendment 2.
4.2 Criterion changed per Amendment 3
4.3 Previously treated with radical prostatectomy with or without lymph node dissection and either
a)For Biochemical recurrence after RP: Any post-operative PSA measurement of <0.1 ng/mL within 12 months after RP and without any PSA =0.1 ng/mL within the 4 to 8-week period after RP. OR
b)For persistent PSA after RP: PSA =0.1 ng/mL within the 4 to 8-week period after RP, confirmed by additional measurement at least 3 weeks later.
5. Criterion deleted per Amendment 2
6. Criterion changed per Amendment 1.
6.1 Criterion changed per Amendment 2.
6.2 Criterion changed per Amendment 3
6.3 High risk of developing metastasis defined as:
a) For biochemical recurrence after RP: pathological Gleason score =8, evaluated from prostate tissue specimen at radical prostatectomy, OR PSADT =12 months at the time of screening.
b) For persistent PSA after RP: Pathological Gleason score =8, evaluated from prostate tissue specimen at radical prostatectomy
7. Criterion changed per Amendment 1.
7.1 Criterion changed per Amendment 3
7.2 Results of PSMA-PET at screening , as determined by BICR, must be:
- PSMA-PET-negative for any prostate cancer lesions (ie, no locoregional lesion and no distant lesions); OR
- PSMA-PET-positive for at least one loco-regional (pelvic) lesion without distant extra pelvic lesion OR
- PSMA-PET-positive for at least one loco-regional (pelvic) lesion with distant extra-pelvic lesion(s)
8. Criterion changed per Amendment 1.
8.1 Criterion changed per Amendment 2.
8.2 Criterion changed per Amendment 3
8.3 Patients with evidence of distant metastasis on screening PSMA-PET scan must have no evidence of prostate cancer 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. Conventional images (99mTc bone scan and CT/MRI) from screening will be evaluated locally before randomization.
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 or growth factors within 1 month prior to randomization.
- Hemoglobin =10.0 g/dL (6.21 mmol/L), without transfusion 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 person of childbearing potential, a condom must be used together with anothe
1. History of pelvic radiation for malignancy.
2. Criterion deleted per Amendment 1.
3. Previous treatment with ADT for prostate cancer.
4. Criterion changed per Amendment 2.
4.1 Previously treated for BCR or persistent PSA after RP (previous surgical treatment of one or more loco-regional lesions is allowed).
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 treatment: 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 treatment (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 & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine if the addition of apalutamide to RT+LHRHa delays metastatic progression as assessed by PSMA-PET or death compared with RT+LHRHa alone.;Secondary Objective: - To determine if the addition of apalutamide to RT+LHRHa provides superior efficacy in other efficacy endpoints compared with RT+LHRHa alone.<br>- To characterize the safety profile of treatment with RT+LHRHa plus apalutamide.;Primary end point(s): PSMA-PET metastatic progression-free survival (ppMPFS): Defined as the time from randomization to the (scan) date of metastatic progression by PSMA PET (as determined by BICR) or death from any cause.<br>;Timepoint(s) of evaluation of this end point: At screening, Month 6, Month 12, then annually until the end of the study. The frequency of PSMA PET assessments will increase as soon as participants reach PSA level =0.2 ng/mL a PSMA-PET assessment will be performed, and then every 6 months until PSMA-PET metastatic progression is confirmed or end of the study.
- Secondary Outcome Measures
Name Time Method