Adaptive Abiraterone Therapy for Metastatic Castration Resistant Prostate Cancer

• ClinicalTrials.gov Identifier: NCT02415621
• Recruitment Status: Active, not recruiting
• First Posted: April 14, 2015
• Last Update Posted: January 4, 2023
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Tracking Information

• First Submitted Date: April 9, 2015
• First Posted Date: April 14, 2015
• Last Update Posted Date: January 4, 2023
• Actual Study Start Date: April 13, 2015
• Actual Primary Completion Date: August 12, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 9, 2015)

Prostatic Specific Antigen (PSA) Response Rate [ Time Frame: End of cycle 2: 2 months per participant ]

PSA response rate (defined as 50% decline of pre abiraterone PSA) at cycle 2. Rate in black participants, non-black participants, and participants overall.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 9, 2015)

• Median Radiographic Progression-Free Survival (rPFS) [ Time Frame: Up to 36 months ]
  Radiographic progression defined by any of the following: 1.) Progression of measureable lesions per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over pretreatment baseline if no decrease during therapy) using the same imaging techniques as baseline, as well as an absolute increase of at least 0.5 cm. 2.) Progression on bone scan is defined as 2 or more new lesions on radionuclide bone scans. 3.) Unequivocal progression evidenced by appearance of 2 or more new measurable lesions at least 2 cm in short axis. Rate in black participants, non-black participants, and participants overall.
• Median Time to Performance Status Deterioration [ Time Frame: Up to 36 months ]
  Median Time to Eastern Cooperative Oncology Group (ECOG) Performance status in deterioration. 0 - Fully active, able to carry on all pre-disease performance without restriction; 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work; 2- Ambulatory and capable of self-care but unable to carry out any work activities; up and about more than 50% of waking hours; 3 - Capable of limited self-care, confined to bed or chair more than 50% of waking hours; 4 - Completely disabled; cannot carry on any self-care; totally confined to bed or chair. Rate in black participants, non-black participants, and participants overall.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Adaptive Abiraterone Therapy for Metastatic Castration Resistant Prostate Cancer
• Official Title: A Pilot Study of Adaptive Abiraterone Therapy for Metastatic Castration Resistant Prostate Cancer

Brief Summary

Abiraterone is approved in the United States by the U.S. Food and Drug Administration (FDA) to treat metastatic prostate cancer at 1000 mg daily.

The purpose of this study is to find out if an on and off schedule of taking abiraterone would prolong the participant's cancer's response to this drug and maintain their functionality to perform their daily activities.

Detailed Description

In this pilot study, 10 black participants and 15 non-black participants will be enrolled after achieving 50% or more decline of their prostatic specific antigen (PSA) while on abiraterone for asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer (mCRPC). Abiraterone will be stopped and will not be re-initiated until there is 50% or more increase of the PSA. Each time abiraterone is stopped, it will be defined as the start of a new adaptive therapy cycle. Participants who cannot achieve a 50% decline of their PSA after restarting abiraterone will continue abiraterone until they develop radiographic disease progression. If the decline in performance status does not occur at the time of radiographic disease progression, participants will be followed until they develop radiographic disease progression.

The study will be terminated early if less than 3 of the first 10 enrolled participants can complete 2 cycles of the adaptive abiraterone.

• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

Drug: Abiraterone Acetate

1000 mg by mouth (PO) every day (QD)

Other Name: Zytiga

Study Arms

Abiraterone Acetate Therapy

Study schedule involves stopping FDA Approved abiraterone after participants achieve a good PSA response (50% or more decline of pre-abiraterone PSA) and then restarting abiraterone after their PSA reaches the level of pre-abiraterone PSA.

Intervention: Drug: Abiraterone Acetate

• Publications *: Zhang J, Cunningham JJ, Brown JS, Gatenby RA. Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer. Nat Commun. 2017 Nov 28;8(1):1816. doi: 10.1038/s41467-017-01968-5.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 24, 2020): 19
• Original Estimated Enrollment (submitted: April 9, 2015): 40
• Estimated Study Completion Date: December 2023
• Actual Primary Completion Date: August 12, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate (the availability archival prostate tumor sample is preferred not required)
• Asymptomatic or minimally symptomatic (not requiring opioids for cancer related pain) metastatic castration resistant prostate cancer (CRPC) patients on abiraterone as standard of care and achieved at least 50% decline of their pre-treatment prostatic specific antigen (PSA)
• Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
• Adequate organ function
• Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections or major surgery within 28 days prior to study enrollment
• Prior surgical castration or concurrent use of gonadotropin-releasing hormone (GnRH) analogue (i.e. medical castration) with testosterone at screening <50 ng/dL.
• Ability to give written informed consent

Exclusion Criteria:

• Except GnRH analogue therapy, any other therapies for prostate cancer (excluding bisphosphonate and denosumab) must be discontinued 3 weeks before the first dose of study drugs.
• Prior treatments with Cyp 17 inhibitors like TAK-700/Orteronel, ketoconazole, radium 223 or docetaxel (up to 6 cycles of docetaxel given in the non CRPC setting is allowed). Prior treatment with Sipuleucel-T is allowed.
• Documented central nervous system (CNS) metastases or liver metastasis
• 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. Potential participants 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: May be rescreened after adjustments of antihypertensive medications
• Unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 [National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03], New York Heart Association (NYHA) 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02415621
• Other Study ID Numbers: MCC-17981
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jingsong Zhang, M.D., Ph.D.; H. Lee Moffitt Cancer Center and Research Institute

• PRS Account: H. Lee Moffitt Cancer Center and Research Institute
• Verification Date: December 2022