Intermittent Androgen Deprivation Therapy for Stage IV Castration Sensitive Prostate Cancer

Sponsor

H. Lee Moffitt Cancer Center and Research Institute (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03511196

Collaborator

(none)

Enrollment

Location

Arm

68.5

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Adaptive Androgen Deprivation Therapy (ADT) plus Standard of Care. The purpose of this study is to develop adaptive therapy for high risk metastatic castration sensitive prostate cancer (mCSPC).

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer Stage IV Prostate Cancer Advanced Prostate Cancer Adenocarcinoma of the Prostate	Drug: Adaptive Androgen Deprivation Therapy (ADT) Drug: Abiraterone Drug: Prednisone	Early Phase 1

Detailed Description

Investigators proposed this pilot feasibility study to use prostate specific antigen (PSA) response and testosterone level to guide the treatment with androgen deprivation therapy (ADT) [Leuprolide, Goserelin, and Triptorelin are the most commonly used GnRH agonists for ADT] and/or abiraterone plus prednisone. Adaptive therapy is a program of chemotherapy where the type and dosage of drug changes in an attempt to kill more of the cancer.

Abiraterone acetate with prednisone is a standard of care treatment for mCRPC (metastatic castration resistant prostate cancer). It works by interrupting the male hormone (androgen) making process in the testes, adrenal glands, and tumors. This helps to prevent the growth of tumors that need these hormones to grow.

Study Design

Study Type:

Interventional

Actual Enrollment :

17 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b Study of Adaptive Androgen Deprivation Therapy for State IV Castration Sensitive Prostate Cancer

Actual Study Start Date :

Sep 17, 2018

Actual Primary Completion Date :

Jun 22, 2022

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adaptive ADT+ Standard of Care Participants will undergo 12-16 weeks of GnRH analog, along with 8-12 weeks of combinational therapy with GnRH analog and abiraterone plus prednisone. 14 participants who achieve >75% PSA decline after the run-in period will be enrolled. GnRH analog and abiraterone will be stopped after study enrollment. PSA and testosterone level will be measured every 4 weeks during the run-in period, then every 6 weeks after study enrollment. Imaging studies with CT and bone scan will be performed at the time of study enrollment and these will be considered baseline scans. Study treatment will be restarted if participant's PSA reaches 2 fold or higher of his baseline PSA. Selection of treatment will be based on participant's testosterone level.	Drug: Adaptive Androgen Deprivation Therapy (ADT) ADT with Leuprolide, Goserelin, or Triptorelin, as GnRH agonist, every 4 weeks as outlined in study arm description. Other Names: GnRH agonist Drug: Abiraterone Prednisone 5 mg once a day with food. Other Names: Standard of Care Zytiga Drug: Prednisone Abiraterone 1000 mg daily with empty stomach. Other Names: Standard of Care Glucocorticoid

Arm

Intervention/Treatment

Experimental: Adaptive ADT+ Standard of Care

Participants will undergo 12-16 weeks of GnRH analog, along with 8-12 weeks of combinational therapy with GnRH analog and abiraterone plus prednisone. 14 participants who achieve >75% PSA decline after the run-in period will be enrolled. GnRH analog and abiraterone will be stopped after study enrollment. PSA and testosterone level will be measured every 4 weeks during the run-in period, then every 6 weeks after study enrollment. Imaging studies with CT and bone scan will be performed at the time of study enrollment and these will be considered baseline scans. Study treatment will be restarted if participant's PSA reaches 2 fold or higher of his baseline PSA. Selection of treatment will be based on participant's testosterone level.

Drug: Adaptive Androgen Deprivation Therapy (ADT)

ADT with Leuprolide, Goserelin, or Triptorelin, as GnRH agonist, every 4 weeks as outlined in study arm description.

Other Names:

GnRH agonist

Drug: Abiraterone

Prednisone 5 mg once a day with food.

Other Names:

Standard of Care

Zytiga

Drug: Prednisone

Abiraterone 1000 mg daily with empty stomach.

Other Names:

Standard of Care

Glucocorticoid

Outcome Measures

Primary Outcome Measures

Rate of Participant Retention [12 months from participant's first dose of ADT]
Percentage of participants who remain on study at month 12. The study will be terminated early if 2 or more of the first 6 enrolled subjects discontinued study due to cancer progression within a year of study enrollment.

Secondary Outcome Measures

Median Time to Progression From the First Dose of Androgen Deprivation Therapy (ADT) [12 months from participant's first dose of ADT]
Median time to prostate specific antigen (PSA) progression while on androgen deprivation therapy (ADT), abiraterone and prednisone. Progression is per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and the Prostate Cancer Clinical Trials Working Group 3 (PCWG3).
Median Time to Radiographic Progression From the First Dose of ADT [12 months from participant's first dose of ADT]
Median time to radiographic progression while on ADT, abiraterone and prednisone. Progression is per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and the Prostate Cancer Clinical Trials Working Group 3 (PCWG3).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed adenocarcinoma of the prostate.
75% prostate specific antigen (PSA) decline after 12 to 16 weeks of run in period with Gonadotropin-releasing Hormone (GnRH) analog abiraterone plus prednisone.
Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
Adequate organ function Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be < 2.5 x upper limit of normal (ULN), total bilirubin less than 1.5 X ULN, estimated creatinine clearance must be >40 mL/min, absolute neutrophil count (ANC) > 1500/l, hemoglobin above 9 g/dl, platelet count > 100,000/l
Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections or major surgery within 28 days prior to study enrollment
Ability to give written informed consent

Exclusion Criteria:

Prior GnRH analog with GnRH analogue for non-metastatic prostate cancer within 12 months prior to study enrollment or >3 months of GnRH analog in the metastatic setting
Prior treatments with TAK-700/Orteronel, ketoconazole, apalutamide or enzalutamide.
Documented central nervous system metastases or liver metastasis
Prior surgical castration
Requiring opioids for cancer related pain.
Treatment with any investigational compound within 30 days prior to the first dose of study drugs
Diagnosis or treatment for another systemic malignancy within 2 years before the first dose of study drugs, or previously diagnosed with another malignancy & have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
Uncontrolled hypertension despite appropriate medical therapy (blood pressure of greater than 160 mmHg systolic and 90 mmHg diastolic at 2 separate measurements no more than 60 minutes apart during the Screening period). Note: Patients may be rescreened after adjustments of antihypertensive medications
Unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 (NCI CTCAE, version 5), New York Association Class III or IV heart failure
Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C not contained with anti-viral therapy, life threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in investigator's opinion, potentially interfere with participation in this study.
Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of study drugs, including difficulty swallowing tables.
Delayed healing of wounds, ulcers, and/or bone fractures
Inability to comply with protocol requirements