Adaptive Abiraterone Therapy for Metastatic Castration Resistant Prostate Cancer
The purpose of this phase II 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.
- 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 PSA
- Performance status ECOG 0-2
- Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be < 2.5 x upper limit of normal (ULN)
- Total bilirubin < 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
- 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
- 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 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; 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 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 4.03), 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 tablets
- Subjects with delayed healing of wounds, ulcers, and/or bone fractures
- Inability to comply with protocol requirements
Locations & Contacts
Contact: Cortlin P. Croft
Trial Objectives and Outline
I. Describe the percentage of abiraterone responsive (defined as 50% decline of prostate specific antigen [PSA]) blacks and non-blacks who remain to be responsive to abiraterone (abiraterone acetate) after completing 2 adaptive treatment cycles.
I. Describe the radiographic progression free survival (rPFS) in blacks and non-blacks undergoing adaptive abiraterone therapy.
II. Describe the time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration in blacks and non-blacks undergoing adaptive abiraterone therapy.
I. Detect the intra-tumor heterogeneity of androgen receptor (AR), cytochrome P450 family 17 (Cyp17), CD86 and CD163 immunohistochemistry (IHC) stains and the gene expression of inflammatory biomarkers, AR and AR related genes on formalin-fixed, paraffin-embedded (FFPE) blocks of prostate tumors.
II. Assess the CYP17 (rs743572) polymorphism among study subjects.
III. Measure the changes in circulating tumor cell (CTC) numbers, HOXB13 status and AR alterations among the isolated CTCs.
IV. Develop a mathematical model for adaptive abiraterone therapy.
V. Health economics of adaptive abiraterone therapy versus standard of care.
VI. To develop imaging habitat biomarkers to track diseases progression using the patients scans and compare with conventional progression variables (like PSA).
VII. Compare the AR, Cyp17 IHC stains as well as imaging biomarkers with a retrospective cohort of metastatic castration-resistant prostate cancer (mCRPC) patients who took daily abiraterone as standard of care.
Beginning when the PSA increases to the pre abiraterone acetate baseline, patients receive abiraterone acetate orally (PO) daily. Abiraterone acetate will be stopped after PSA declines to 50% or more below its baseline. Each time abiraterone acetate is stopped, it will be defined as the start of a new adaptive therapy course. Courses repeat in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 4-6 weeks or more frequently if clinically indicated.
Trial Phase & Type
Moffitt Cancer Center
Secondary IDs NCI-2015-00648, 15.01.0005, MCC17981
Clinicaltrials.gov ID NCT02415621