Clinical Trials /

Intermittent Androgen Deprivation Therapy for Stage IV Castration Sensitive Prostate Cancer

NCT03511196

Description:

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).

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Intermittent Androgen Deprivation Therapy for Stage IV Castration Sensitive Prostate Cancer
  • Official Title: A Phase 1b Study of Adaptive Androgen Deprivation Therapy for State IV Castration Sensitive Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: MCC-19367
  • NCT ID: NCT03511196

Conditions

  • Prostate Cancer
  • Stage IV Prostate Cancer
  • Advanced Prostate Cancer
  • Adenocarcinoma of the Prostate

Interventions

DrugSynonymsArms
Adaptive Androgen Deprivation Therapy (ADT)GnRH agonistAdaptive ADT+ Standard of Care
AbirateroneStandard of Care, ZytigaAdaptive ADT+ Standard of Care
PrednisoneStandard of Care, GlucocorticoidAdaptive ADT+ Standard of Care

Purpose

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).

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.
    

Trial Arms

NameTypeDescriptionInterventions
Adaptive ADT+ Standard of CareExperimentalParticipants 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.
  • Adaptive Androgen Deprivation Therapy (ADT)
  • Abiraterone
  • Prednisone

Eligibility Criteria

        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, abiraterone, 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of Participant Retention
Time Frame:12 months from participant's first dose of ADT
Safety Issue:
Description: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

Measure:Median Time to Progression From the First Dose of Androgen Deprivation Therapy (ADT)
Time Frame:12 months from participant's first dose of ADT
Safety Issue:
Description: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).
Measure:Median Time to Radiographic Progression From the First Dose of ADT
Time Frame:12 months from participant's first dose of ADT
Safety Issue:
Description: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).

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • stage IV castration sensitive prostate cancer
  • advanced castration sensitive prostate cancer

Last Updated

September 5, 2019