Localized or a locally advanced high-risk prostate cancer MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
VÝCHODOSLOVENSKÝ ONKOLOGICKÝ ÚSTAV, a.s.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Subject must be a man in the age of 18 – 79 years; 2. Each subject must sign an informed consent form (ICF) indicating that he understands the purpose and procedures required for the study and is willing to participate in the study. Subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol. 3. Indicated and planned to receive primary RT for prostate cancer; 4. Histologically confirmed adenocarcinoma of an intact prostate and one of the following risk factors for EUA high-risk localized or locally prostate cancer (see Attachment 1) at diagnosis: • Localized high-risk prostate cancer: PSA >20 ng/ml or GS >7 (ISUP grade 4/5) or cT2c • Locally advanced high-risk prostate cancer: cT3 – 4 or cN+, any PSA, any ISUP grade Note: Documentation of clinical T stage (cT2c, cT3, cT4) may be obtained from any clinical assessment acceptable for clinical T staging including digital rectal examination (DRE) and MR. Documentation of N and M stage may be obtained from conventional imaging (technetium bone scan, and prostate MR or abdominopelvic CT) or molecular imaging (68Ga PSMA PET/CT). 5. Modified Charlson comorbidity index (CCI) =4 (Attachment 2); 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade 0 or 1 (Attachment 2); 7. Adequate organ function determined by the following local laboratory values: • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5x upper limit of normal (ULN); total bilirubin =1.5x ULN, • Serum creatinine =2x ULN, • Thrombocytes =140x10^9/l, • Hemoglobin =120 g/l (no transfusion is allowed within 3 months prior to enrollment); 8. To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must use a condom during sexual activity while on study drug and for 3 months following the last dose of study drug. Donation of sperm is not allowed during the Treatment Phase and for 3 months following the last dose of study drug. 9. Be able to swallow whole study drug tablets, undergo prostate MR, prostate seeds implantation and prostate radiotherapy in supine position. 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 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Presence of distant metastasis on conventional imaging or 68Ga PSMA/PET (clinical stage M1). Isolated pelvic nodal disease below the iliac vessels bifurcation (clinical stage N1) is not an exclusion. 2. Prior treatment with LHRH agonist/antagonist analogue or anti-androgen or both for >3 months prior to enrollment; 3. Bilateral orchiectomy; 4. History of pelvic radiation; 5. Prior systemic (e.g., chemotherapy) or local (e.g., radical prostatectomy, cryotherapy) treatment for prostate cancer; 6. Prior treatment with enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents (including cyproterone acetate) for prostate cancer; 7. Prior treatment with systemic glucocorticoids =4 weeks prior to enrollment or subject expected to require long-term use of corticosteroids during the study; 8. Use of first-generation antiandrogen (e.g., bicalutamide) =4 weeks prior to enrollment; 9. Use of 5-a reductase inhibitors (e.g., dutasteride, finasteride) =4 weeks prior to enrollment; 10. Use of any investigational agent =4 weeks prior to enrollment; 11. Current chronic use of opioid analgesics, for =3 weeks for oral or =7 days for non-oral formulations; 12. Major surgery =4 weeks prior to enrollment; 13. 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 enrollment; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect); 14. Current or prior treatment with anti-epileptic medications for the treatment of seizures; 15. Gastrointestinal conditions affecting absorption; 16. Known or suspected contraindications or hypersensitivity to apalutamide or LHRH agonists/antagonist 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 subject.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is the assessment of efficacy and safety of the combination of ADT, apalutamide and stereotactic radiotherapy on the localized or locally advanced high-risk prostate cancer. Efficacy assessment is determined by the biochemical control rate after 5 years, and biochemical progression is defined according to RTOG – ASTRO Phoenix consensus criteria (a rise by 2 ng/mL or more above the nadir PSA with the date of failure determined "at call"). Safety assessment is determined by the rate of clinically significant G2 and G3 gastrointestinal and genitourinary toxicity. ;Secondary Objective: The secondary objectives are the assessment of patient´s quality of life using the validated questionnaires, and the assessment of metastasis free survival based on 68Ga PSMA PET/CT. Time to distant metastasis is defined as the time from enrollment to the date of the first occurrence of bone or soft tissue distant metastasis on 68Ga PSMA PET/CT. ;Primary end point(s): 5 –year biochemical control rate defined as a percentage of surviving patients without biochemical progression after 5 years since the treatment start (assessed by Kaplan-Meier estimate) ;Timepoint(s) of evaluation of this end point: 7 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Major secondary endpoint: Metastasis free survival based on PSMA PET/CT (assessed by Kaplan-Meier estimate). Time to distant metastasis is defined as the time from enrollment to the date of the first occurrence of radiographic or pathological bone or soft tissue distant metastasis 68Ga PSMA PET/CT Other secondary endpoints: 5 –year biochemical control rate with PSA <0.2 ng/mL 5 –year prostate cancer specific survival 5 – year overall survival (OS). OS is defined as the time from enrollment to date of death from any cause. Incidence of acute and late side effects and complications associated with radiotherapy and systemic treatment evaluated by Common Terminology Criteria of Adverse Event (CTC AE) and Patient Reported Outcomes (PRO) including QoL questionnaires Effect of the planned interventions on QoL (I-PSS, EPIC-26, FACT-P, EQ-5D-5L, PRO-CTCAE™ (short version)) ;Timepoint(s) of evaluation of this end point: 7 years | — |
Countries
Slovakia
Contacts
Public ContactMUDr. Beata Cecetková, PhD.
TWMA, s.r.o.
Outcome results
None listed