NCT02811809

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

Apalutamide Plus Intermittent Hormone Therapy (IHT) Versus IHT Alone in Prostate Cancer Patients With Biochemical Recurrence

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: The University of Texas Health Science Center, Houston · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Detailed description

Prostate-specific antigen (PSA) is a sensitive and specific biomarker of prostate tissue. Monitoring of PSA after local treatment for prostate cancer can assist in identifying patients who have only increased PSA (biochemical recurrence \[BCR\]) despite no symptoms, signs, or evidence of radiographic metastatic disease. This subpopulation of patients are referred to as having "biochemical failure." 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, diabetes, heart disease, metabolic syndromes 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, owing to the removal of constant pressure causing faster mutation of resistant cells; (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 antitumor drug, taken by mouth. It is a synthetic compound rationally designed to bind the androgen receptor (with higher affinity than enzalutamide or bicalutamide), prevent both nuclear translocation and DNA binding, and induce apoptosis. It has greater antitumor activity at a lower dose, achieves steady-state levels at a lower dose, and accumulates more into tumor tissue without building up in the brain, which both increases effectiveness and decreases the risk of seizure. Apalutamide's mechanism of action gives it the potential to extend the time to PSA increase during intermittent ADT, delaying the necessity for continuous ADT. Investigators will assess the potential applications of intermittent ADT plus Apalutamide for participants with BCR. This study will elucidate the potential of this regimen to reduce the burden of adverse events of continuous ADT and delay the development of hormone resistance. This is a randomized crossover study intended to determine the interval of ADT administration achievable with supportive Apalutamide treatment. Investigators will assess the significance of time to PSA recurrence, time to next leuprolide injection, time to testosterone recovery, duration of testosterone recovery, time to biochemical recurrence, percentage of men developing biochemical recurrence, number of detectable CTCs, and quality of life measures. Treatment will be 66 participants in 2:1 randomized crossover - 45 IHT + apalutamide:21 IHT only until second leuprolide injection, then IHT + apalutamide Apalutamide + IHT Participants will be treated with 240 mg (4 60 mg tablets) oral Apalutamide daily plus 22.5 mg 3-month depot intramuscular leuprolide intermittently. IHT Participants will receive 22.5 mg 3-month depot intramuscular leuprolide until PSA progression, when they will receive 240 mg oral Apalutamide daily plus 22.5 mg 3-month depot intramuscular leuprolide intermittently. Participants remain on study until continuous ADT is required to maintain castrate PSA levels (i.e., leuprolide is needed every 3 months to maintain PSA \<1 ng/dL).

Conditions

• Prostate Cancer

Interventions

Type	Name	Description
DRUG	Apalutamide	Apalutamide 240 mg (4 60mg tablets) daily
DRUG	IHT	Leuprolide 3-month depot 22.5 intramuscular dose

Timeline

• Start date: 2020-12-01
• Primary completion: 2024-12-01
• Completion: 2025-12-01
• First posted: 2016-06-23
• Last updated: 2020-02-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study