Back to resultsIntermittent Androgen Deprivation Therapy for Stage IV Castration Sensitive Prostate Cancer
Primary Purpose
Prostate Cancer, Stage IV Prostate Cancer, Advanced Prostate Cancer
Status
Active
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Adaptive Androgen Deprivation Therapy (ADT)
Abiraterone
Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring stage IV castration sensitive prostate cancer, advanced castration sensitive prostate cancer
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, 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
Sites / Locations
- H. Lee Moffitt Cancer Center and Research Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Adaptive ADT+ Standard of Care
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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).
Full Information
NCT ID
NCT03511196
First Posted
April 18, 2018
Last Updated
October 18, 2023
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT03511196
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 17, 2018 (Actual)
Primary Completion Date
June 22, 2022 (Actual)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Stage IV Prostate Cancer, Advanced Prostate Cancer, Adenocarcinoma of the Prostate
Keywords
stage IV castration sensitive prostate cancer, advanced castration sensitive prostate cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Adaptive ADT+ Standard of Care
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Adaptive Androgen Deprivation Therapy (ADT)
Other Intervention Name(s)
GnRH agonist
Intervention Description
ADT with Leuprolide, Goserelin, or Triptorelin, as GnRH agonist, every 4 weeks as outlined in study arm description.
Intervention Type
Drug
Intervention Name(s)
Abiraterone
Other Intervention Name(s)
Standard of Care, Zytiga
Intervention Description
Prednisone 5 mg once a day with food.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
Standard of Care, Glucocorticoid
Intervention Description
Abiraterone 1000 mg daily with empty stomach.
Primary Outcome Measure Information:
Title
Rate of Participant Retention
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.
Time Frame
12 months from participant's first dose of ADT
Secondary Outcome Measure Information:
Title
Median Time to Progression From the First Dose of Androgen Deprivation Therapy (ADT)
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).
Time Frame
12 months from participant's first dose of ADT
Title
Median Time to Radiographic Progression From the First Dose of ADT
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).
Time Frame
12 months from participant's first dose of ADT
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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, 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jingsong Zhang, M.D., Ph.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
36358643
Citation
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 Oct 25;14(21):5225. doi: 10.3390/cancers14215225.
Results Reference
result
Links:
URL
https://www.moffitt.org/clinical-trials-research/clinical-trials/
Description
Moffitt Cancer Center Clinical Trials website
Learn more about this trial
Intermittent Androgen Deprivation Therapy for Stage IV Castration Sensitive Prostate Cancer
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