A Study of an Intermittent ADT Approach with Apalutamide Monotherapy in Participants with mCSPC

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

22 Nov 2023 → ongoing

Decision date (initial)

2023-09-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacogenomic, Efficacy

To determine if the intermittent use of ADT provides non-inferior radiographic progression-free survival (rPFS) measured by 18-month event-free survival and reduce the burden of hot flash measured as 18-month severity adjusted hot flash score for participants with mCSPC who reached PSA <0.2 ng/mL after 6 months of treatment with apalutamide and ADT combination therapy

Conditions and MedDRA coding

Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. 1. Be ≥18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater) at the time of informed consent.
2. 10. Participants should have: - Hemoglobin ≥9.0 g/dL, without transfusion or growth factors within 1 week - Neutrophils ≥1.0 x 103/μL - Platelets ≥50 x 103/μL, without transfusion or growth factors within 1 week
3. 11. Human immunodeficiency virus-positive participants are eligible if they meet all of the following: a. No detectable viral load (ie, <50 copies/mL) at screening b. CD4+ count >300 cells/mm3 at screening c. No acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of screening d. Receiving highly active antiretroviral therapy (HAART). Any changes in HAART due to resistance/progression should occur at least 3 months prior to screening. A change in HAART due to toxicity is allowed up to 4 weeks prior to screening. Note: HAART that could interfere with study treatment is excluded (consult the sponsor for a review of medications prior to enrollment).
4. 12. A participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for at least 3 months after receiving the last dose of study treatment. If the participant’s partner is a person of childbearing potential, the participant must use condoms (with or without spermicide) and the sexual partner of the participant must also be practicing a highly effective method of contraception where conception is possible. A vasectomized participant must still use a condom (with or without spermicide) and the partner is also required to use a highly effective method of contraception where conception is possible
5. 13. A participant must agree not to donate sperm for the purposes of reproduction during the study and for at least 3 months after receiving the last dose of study treatment. If applicable, participants should consider preservation of sperm prior to study treatment as anti-cancer treatments may impair fertility.
6. 14. A participant must agree not to plan to conceive a child while enrolled in this study or within 3 months after the last dose of study treatment.
7. 15. Criterion amended per Amendment 1
8. 16. Be willing and able to adhere to the lifestyle restrictions specified in this protocol.
9. 17. Must be able to take whole apalutamide tablets by swallowing alone or with another vehicle (eg, applesauce).
10. 2. Diagnosis of prostate cancer prior to screening with histologically or cytologically confirmed adenocarcinoma of the prostate.
11. 3. Criterion amended per Amendment 2 3.1a For participants not undergoing Gender-affirming care: Metastatic prostate cancer disease documented by conventional imaging (eg, CT, MRI, or bone scan) and/or NGI demonstrating ≥2 distinct extraprostatic sites of metastasis. Note: When historical conventional imaging is not available, baseline examination must be done during screening. 3.1b For participants undergoing Gender-affirming care: No evidence of metastasis by either conventional imaging (eg, CT, MRI, or bone scan) and/or NGI is also acceptable.
12. 4. No pathologic finding consistent with small cell, ductal, or neuroendocrine carcinoma of the prostate.
13. 5. Criterion amended per Amendment 2 5.1a For Participants not undergoing Gender-affirming care: Testosterone levels >50 ng/dL at screening, except for those who may have received ADT prior to screening. Participants are allowed to have received up to 3 months of ADT prior to enrollment. 5.1b For Participants undergoing Gender-affirming care: There is no testosterone level requirement for inclusion.
14. 6. Can have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
15. 7. Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. Participants with ECOG PS 2 or 3 are eligible for the study if the ECOG PS score is related to stable physical limitations (eg, wheelchair-bound due to prior spinal cord injury) and not related to prostate cancer or associated therapy.
16. 8. Participants with no underlying hepatic metastases are eligible if they have: - Aspartate aminotransferase (AST) <3 x upper limit of normal (ULN) - Alanine aminotransferase (ALT) <3 x ULN - Total bilirubin <1.5 x ULN (isolated total bilirubin ≥1.5 x ULN with conjugated [direct] bilirubin <1.5 xULN is allowed for those participants with known congenital nonhemolytic hyperbilirubinemias)
17. 9. Participants with known hepatic metastases are eligible if they have: - AST <5 x ULN - ALT <5 x ULN - Total bilirubin <3 x ULN (isolated total bilirubin ≥3 x ULN with conjugated [direct] bilirubin <1.5 x ULN is allowed for those participants with known congenital nonhemolytic hyperbilirubinemias)
18. 15.1 Must sign 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.

Exclusion criteria 18

1. 1. History of seizure or known condition that has been determined to significantly predispose to seizure per investigator (including, but not limited to, loss of consciousness within 1 year prior to screening, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect).
2. 10. Treatment with drugs known to lower the seizure threshold within 4 weeks prior to enrollment.
3. 11. Current or prior treatment with anti-epileptic medications for the treatment of seizures.
4. 12. Prior treatment with next-generation anti-androgens (eg, apalutamide, darolutamide, enzalutamide), cytochrome P450 (CYP)17 inhibitors (eg, abiraterone acetate), chemotherapy for metastatic prostate cancer, immunotherapy (eg, sipuleucel-T), or radiopharmaceutical agents, or other treatments for prostate cancer except those listed in exclusion criteria #8.
5. 13. Participants who have undergone a bilateral orchiectomy with the exception of participants who completed this as part of their gender-affirming care or a result of a variation in physical sex development.
6. 14. Criterion amended per Amendment 1
7. 15. a. Active hepatitis of infectious origin. Seropositive for hepatitis B: defined by a positive test for hepatitis B surface antigen (HBsAg). Participants with resolved infection (ie, participants who are HBsAg negative with positive antibodies to total hepatitis B core antigen [anti-HBc] must be screened using real-time polymerase chain reaction (RT-PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are RT-PCR positive will be excluded. Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by RT-PCR. b. Known hepatitis C infection or positive serologic testing for hepatitis C virus (anti- HCV antibody). Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C ribonucleic acid (RNA) test is obtained at screening or within 3 months prior to first dose of study treatment. c. Other clinically active liver disease of infectious origin.
8. 16. Criterion amended per Amendment 1
9. 2. Pelvic lymph nodes as only site of metastasis (defined as N1 disease = metastasis in regional lymph node(s); regional = true pelvic nodes below the bifurcation of common iliac arteries).
10. 3. Known allergies, hypersensitivity, or intolerance to excipients of apalutamide (refer to the IB).
11. 4. Any of the following within 6 months prior to screening: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, uncontrolled, hypertension, clinically significant 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.
12. 5. Gastrointestinal disorder affecting absorption.
13. 6. Participant has active (new or progressive) brain metastases for whom the treating physician determines that central nervous system (CNS) specific treatment is required immediately or during the first cycle of therapy. Those with active (new or progressive) brain metastases for whom the treating physician determines that CNS specific treatment is not required immediately or during the first cycle of therapy are eligible for inclusion.
14. 7. Participant with leptomeningeal disease-related to cancer.
15. 8. Prior treatment for metastatic prostate cancer, with the exception of ≤3 months of ADT combined with focal radiation to an oligometastatic site since the diagnosis of mCSPC. Note: 1 single course of palliative radiotherapy will be allowed prior to screening for symptomatic bone metastases (it can be conventional or stereotactic radiosurgery/stereotactic body radiotherapy). This course must have been completed at least 14 days prior to Screening. Note: Participants who received localized treatment for prostate cancer are eligible to enter the study. For localized or locally advanced prostate cancer, participants must have received ≤3 years total of ADT and all other forms of prior systemic therapies for prostate cancer and all such therapies were completed ≥1 year prior to the first dose of apalutamide (except for participants who receive gender-affirming hormone therapy or exogenous hormones as part of gender-affirming care or a result of a variation in physical sex development).
16. 9. Participant who received surgical intervention for the treatment of prostate cancer within 28 days of study drug initiation. Note: Participants are permitted to receive high dose radiotherapy (eg, palliative) to the prostate as part of their treatment plan as directed by their treating physician. However, participants should not receive high dose radiotherapy (eg, palliative) to the prostate within 4 weeks prior to randomization and 4 weeks after randomization.
17. 14.1 Received an investigational treatment, blood product support, growth factor support or invasive surgical procedure (not including surgical castration) within 28 days or 5 half-lives (whichever is longer) before the planned first dose of study treatment or is currently enrolled in an investigational study.
18. 16.1 Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. France Only: Protected Persons as defined by articles L. 1121-5 to L.1121-8 of the Public Health Code.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. - 18-month radiographic progression-free survival rate. Radiographic progression will be assessed by investigators using conventional imaging - 18-month percent change in severity adjusted hot flash score

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 6

Locations

3 EU/EEA countries · 16 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 65 files

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

Application history

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