Apalutamide, Radiotherapy and LHRH Agonist in High-Risk Hormone-Sensitive Prostate Cancer Patients Assessed by PSMA-PET

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Nov 2020 → ongoing

Decision date (initial)

2024-03-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Janssen Pharmaceutica NV

External identifiers

EU CT number

2023-505852-23-00

EudraCT number

2019-002957-46

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

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.

Conditions and MedDRA coding

High risk recurrent prostate cancer previously treated with radical prostatectomy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 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. 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. 3. Histologically confirmed adenocarcinoma of the prostate.
4. 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. 5. Criterion deleted per Amendment 2
6. 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. 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. 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. 9. Eastern Cooperative Oncology Group Performance Status Grade 0 or 1.
10. 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. 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. 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 another highly effective method of contraception during the Treatment Period and for 3 months after the last dose of study drug.
13. 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 drug.
14. 14. Criterion added per Amendment 1. Participants receiving bone-loss prevention treatment with bone-sparing agents indicated for the treatment of osteoporosis at doses and dosing schedules appropriate for the treatment of osteoporosis (eg, denosumab [Prolia®], zoledronic acid [Reclast®]) must be on stable doses for at least 4 weeks before randomization.
15. 15.Criterion added per Amendment 2. Participant is indicated and planned to receive whole pelvic SRT for BCR prostate cancer.

Exclusion criteria 20

1. 1. History of pelvic radiation for malignancy.
2. 2. Criterion deleted per Amendment 1.
3. 3. Previous treatment with ADT for prostate cancer.
4. 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. 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. 6. Pathological finding consistent with small cell, or neuroendocrine carcinoma of the prostate.
7. 7. Any of the following within 6 months prior to firial infarction, symptomatist dose of study treatment: severe or unstable angina, myocardc 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. 8. Use of 5-alpha-reductase inhibitor ≤4 weeks prior to randomization.
9. 9. Use of investigational agent ≤4 weeks prior to randomization.
10. 10. Not applicable; criterion numbering omitted from initial protocol in error.
11. 11. Prior chemotherapy for prostate cancer.
12. 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. 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. 14. Chronic, active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction.
15. 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. 16. Treatment with drugs known to lower the seizure threshold within 4 weeks prior to randomization.
17. 17. Known or suspected contraindications or hypersensitivity to apalutamide, LHRH agonist or any of the components of the formulations.
18. 18. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant.
19. 19. Criterion deleted per Amendment 1.
20. 20.Criterion added per Amendment 2. Any evidence of prostate cancer metastasis on CT/MRI of the chest/abdomen/pelvis or 99mTc whole-body bone scan, at any time prior to screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen - Cilag International

Sponsor organisation

Janssen - Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Third parties 3

Locations

13 EU/EEA countries · 72 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 46 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications