Apalutamide Plus Intermittent Hormone Therapy Versus Intermittent Hormone Therapy Alone in Prostate Cancer

• Status: Withdrawn
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: Male

Summary

This study is open to men who have biochemical recurrence (BCR, increased PSA) following local treatment of their prostate cancer. Androgen deprivation therapy (ADT) is a standard treatment option, but is only effective for 16-24 months and has a number of side effects that impact quality of life. These side effects may include fatigue, hot flushing, loss of sex drive, brain fog, decreased bone mineral density, loss of muscle mass, mild anemia (low levels of red blood cells that can make people feel tired and weak), diabetes (low blood sugar), heart disease, metabolic syndromes (sometimes called "pre-diabetes" and includes obesity, increased blood pressure, high levels of cholesterol and triglycerides in blood), and risk of fractures. An alternative to continuous ADT is intermittent administration, where patients are given "breaks" from ADT to let their testosterone levels return to baseline. There are a number of potential benefits to intermittent hormone therapy (IHT): (1) longer time to the development of resistance; (2) improved patient quality of life owing to recovery from adverse effects, particularly sexual function; and (3) substantial cost savings owing to less time spent receiving medication. Leuprolide is the name of the ADT / IHT drug.

Apalutamide is an investigational drug, which means it has not been approved by the Food and Drug Administration (FDA). It is an antitumor drug, taken by mouth. The purpose of this study is to determine the ability of Apalutamide to extend the time between the first two injections of leuprolide and improve quality of life. This study will also look at the safety of Apalutamide and the effects that Apalutamide has on prostate cancer.

Men will be randomized (like flipping a coin) to receive:

• Group A: Leuprolide + Apalutamide or

• Group B: Leuprolide only (until second leuprolide injection), then leuprolide + Apalutamide 45 men will be in Group A and 21 men will be in Group B. Leuprolide is given as an intramuscular shot that lasts for 3 months intermittently and Apalutamide is taken by mouth (4 tablets) daily. Each cycle is 4 weeks long.

Intermittent treatment with Apalutamide + leuprolide will continue until continuous leuprolide is needed to maintain undetectable PSA levels (i.e., PSA levels rise above undetectable level unless leuprolide is given without pause, every 3 months).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Robert J Amato; The University of Texas Health Science Center, Houston
• Collaborator: Janssen Scientific Affairs, LLC
• Treatments: Hormones; Leuprolide

Criteria

Inclusion Criteria:

• Age ≥ 18 years

• Patients with a diagnosis of adenocarcinoma of the prostate

• Patients with BCR (PSA becomes detectable, with absolute value ≥1) following prostatectomy who have no evidence of metastatic disease based on radiographic assessment.

• Patients with BCR following radiation therapy who have no radiographic involvement per mpMRI and CT (RTOG-ASTRO Phoenix criteria), size of pelvic nodes ≤1 cm, and whose MRI-directed prostate biopsies are negative.

• Patients must be free of serious comorbidity as determined by investigator.

• Clinical laboratory values at screening:

• Serum testosterone level ≥150 ng/dL

• Hemoglobin ≥9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization

• Platelet count ≥100,000 /µL independent of transfusion and/or growth factors within 3 months prior to randomization

• Serum albumin ≥3.0 g/dL

• GFR >45 mL/min

• Serum potassium ≥3.5 mmol/L

• Serum total bilirubin ≤1.5 × ULN (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN

• Medications known to lower the seizure threshold (see list under prohibited meds, Appendix 3) must be discontinued or substituted at least 4 weeks prior to study entry.

• Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.

• Written, informed consent to participate in this study.

Exclusion Criteria:

• PSA doubling time >12 months

• Positive for HIV or chronic hepatitis B or hepatitis C infection

• Another primary malignancy that has not been in remission for at least 2 years. Non-melanoma skin cancer allowed.

• Use of herbal products that may decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within 4 weeks of screening laboratory studies.

• Any other condition, including concurrent medical condition, social circumstance or drug dependency, which in the opinion of the investigator could compromise patient safety and/or compliance with study requirements

• History of any of the following:

• Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)

• 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 within 6 months prior to randomization Any condition that in the opinion of the investigator, would preclude participation in this study

• Current evidence of any of the following:

• Uncontrolled hypertension

• Gastrointestinal disorder affecting absorption

• Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis) Any condition that in the opinion of the investigator, would preclude participation in this study