Intermittent Androgen Deprivation Therapy for Stage IV Castration Sensitive Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03511196
• Other study ID #: MCC-19367
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: September 17, 2018
• Est. completion date: June 2024

Study information

• Verified date: February 2024
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 17
• Est. completion date: June 2024
• Est. primary completion date: June 22, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma of the Prostate
• Advanced Prostate Cancer
• Hypersensitivity
• Prostate Cancer
• Prostatic Neoplasms
• Stage IV Prostate Cancer

Intervention

Drug:
• Adaptive Androgen Deprivation Therapy (ADT)
ADT with Leuprolide, Goserelin, or Triptorelin, as GnRH agonist, every 4 weeks as outlined in study arm description.
• Abiraterone
Prednisone 5 mg once a day with food.
• Prednisone
Abiraterone 1000 mg daily with empty stomach.

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (1)

Zhang J, Gallaher J, Cunningham JJ, Choi JW, Ionescu F, Chatwal MS, Jain R, Kim Y, Wang L, Brown JS, Anderson AR, Gatenby RA. A Phase 1b Adaptive Androgen Deprivation Therapy Trial in Metastatic Castration Sensitive Prostate Cancer. Cancers (Basel). 2022 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Participant Retention	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.	12 months from participant's first dose of ADT
Secondary	Median Time to Progression From the First Dose of Androgen Deprivation Therapy (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).	12 months from participant's first dose of ADT
Secondary	Median Time to Radiographic Progression From the 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).	12 months from participant's first dose of ADT

External Links

•   Moffitt Cancer Center Clinical Trials website