Castration Resistant Prostate Cancer Clinical Trial
Official title:
A Phase II Study of Increased-Dose Abiraterone Acetate in Patients With Castration Resistant Prostate Cancer (CRPC)
Verified date | August 2020 |
Source | University of California, San Francisco |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The purpose of this study is to find out what effects, good and/or bad,an increased dose of Abiraterone Acetate in combination with prednisone has on patients and their prostate cancer. This study will investigate whether an increased-dose (2,000mg daily) is safe and potentially effective when given to patients whose cancer has grown while taking the standard dose.
Status | Completed |
Enrollment | 41 |
Est. completion date | February 27, 2017 |
Est. primary completion date | February 27, 2017 |
Accepts healthy volunteers | No |
Gender | Male |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Have signed an informed consent document indicating that the subjects understands the purpose of and procedures required for the study and are willing to participate in the study - Be willing/able to adhere to the prohibitions and restrictions specified in this protocol - Written Authorization for Use and Release of Health and Research Study Information has been obtained - Male aged 18 years and above - Able to swallow the study drug whole as a tablet - Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken - Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 1 week after last study drug administration. - Have a baseline serum potassium of = 3.5 milliequivalents per litre (mEq/L) - Have aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin levels < 1.5 x upper limit of normal (ULN) - Have a serum albumin of = 3.0 g/dL - Total bilirubin = 1.5 x ULN (In patients with known Gilbert Syndrome, a total bilirubin = 3.0 x ULN, with direct bilirubin = 1.5 x ULN is acceptable) - Have a platelet count of = 100,000/µL - Have an absolute neutrophil count of > 1500 cell/mm3 - Have a calculated creatinine clearance = 60 mL/min - Have a hemoglobin of = 9.0 g/dL - Have histologically confirmed adenocarcinoma of the prostate. - No prior therapy with chemotherapy for metastatic prostate cancer. - Have metastatic disease based on a positive bone scan or objective imaging on CT scan. - Have ongoing gonadal androgen deprivation therapy with Luteinizing hormone-releasing hormone (LHRH) analogues or orchiectomy. Patients who have not had an orchiectomy must be maintained on effective LHRH analogue therapy for the duration of the trial. - Testosterone < 50 ng/dL. - Progressive disease after androgen deprivation: PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least 2 weeks apart. If the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to document progression. - Antiandrogen Withdrawal (AAWD): Patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen. - Disease progression after antiandrogen withdrawal is defined as 2 consecutive rising PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue progression. - For patients receiving flutamide, at least one of the PSA values must be obtained 4 weeks or more after flutamide discontinuation. - For patients receiving bicalutamide or nilutamide, at least one of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation. - No antiandrogen withdrawal response is expected in patients in whom antiandrogen therapy did NOT result in a decline in PSA or in those patients in whom the response to antiandrogens was < 3 months. Therefore, it is not necessary to wait for AAWD in patients without PSA decline on an anti-androgen or in those in whom a PSA response lasted < 3 months. - Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 - Life expectancy of = 12 weeks. Exclusion Criteria: - Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated - Known brain metastasis - Uncontrolled hypertension (systolic BP = 160 mmHg or diastolic BP = 95 mmHg) Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment - Active or symptomatic viral hepatitis or chronic liver disease - History of pituitary or adrenal dysfunction - Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50 % at baseline - Atrial Fibrillation, or other cardiac arrhythmia requiring medical therapy - Administration of an investigational therapeutic within 30 days of screening - Have poorly controlled diabetes - Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents - Have a pre-existing condition that warrants long-term corticosteroid use in excess of study dose - Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients - Any condition which, in the opinion of the investigator, would preclude participation in this trial. - Pure small cell carcinoma of the prostate or any mixed histology cancer of the prostate (eg: neuroendocrine) which contains < 50% adenocarcinoma. - Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid within 4 weeks prior to first dose of study drug. - Prior therapy with Abiraterone Acetate or other CYP17 inhibitor(s) including TAK-700 or TOK-001, or investigational agent(s) targeting the androgen receptor for metastatic prostate cancer. - Prior therapy with ketoconazole for > 2 weeks for prostate cancer. - Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug, except for any combination of the following: - Conventional multivitamin supplements - Selenium - Lycopene - Soy supplements - Prior radiation therapy completed < 4 weeks prior to enrollment - Prior chemotherapy for castration resistant prostate cancer. Patients who have received chemotherapy for early stage prostate cancer (e.g. as part of a neoadjuvant or adjuvant trial) or for other malignancies are eligible provided that >1 year has passed since the administration of the last chemotherapy dose. - Any "currently active" second malignancy, other than non-melanoma skin cancer. Patients are not considered to have a "currently active" malignancy, if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse over next year. - Active psychiatric illnesses/social situations that would limit compliance with protocol requirements. - Patients in whom urgent chemotherapy, in the opinion of the treating physician, is indicated should not be enrolled in this study. |
Country | Name | City | State |
---|---|---|---|
United States | Oregon Health and Science University | Portland | Oregon |
United States | University of California, San Francisco | San Francisco | California |
Lead Sponsor | Collaborator |
---|---|
Terence Friedlander, MD | Janssen Biotech, Inc. |
United States,
Friedlander TW, Graff JN, Zejnullahu K, Anantharaman A, Zhang L, Paz R, Premasekharan G, Russell C, Huang Y, Kim W, Aggarwal RR, Lin AM, Fong L, Alumkal JJ, Beer TM, Sharifi N, Alyamani M, Dittamore R, Small EJ, Paris PL, Ryan CJ. High-Dose Abiraterone Ac — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Patients With PSA Response From Dose Escalation | A PSA response for the dose escalation group is defined as a participant with a documented PSA decline after 12 weeks of therapy with standard-dose, then had disease progression, and then achieved a =30% PSA decline after 12 weeks from the start of dose escalation therapy. | Up to 12 weeks from start of dose escalation | |
Secondary | Number of Participants With Worst-grade, Treatment-related Toxicities for Dose Escalation Group | Frequency of any treatment-related toxicity with increased-dose Abiraterone Acetate by maximum observed grade will be tabulated for the study cohort. Toxicities will be graded for management according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 as a measure of patient safety. | Up to 24 months | |
Secondary | Time to PSA Progression for Dose Escalation Cohort | Time to PSA progression as defined by RECIST criteria or by the Prostate Cancer Working Group 2 (PCWG) criteria for patients whom were treated with increased dose Abiraterone Acetate. | up to 24 months | |
Secondary | Progression Free Survival for Dose Escalation Cohort | Progression free survival for patients treated with increased dose Abiraterone Acetate | up to 24 months | |
Secondary | Serum Concentration Levels of Abiraterone Acetate Over Time | Pharmacokinetic assessment at the initiation of standard dose therapy, at the time of initial disease progression, at the time of a response to increased dose of abiraterone acetate and at the time of disease progression on increased-dose therapy. | Up to 24 months | |
Secondary | Correlation of Circulating Testosterone Levels at Baseline and Week 12 | Pearson's correlation coefficients ("r") will be calculated to summarize the relationship between testosterone values at baseline and at 12 weeks. Testosterone labs will be obtained at an earlier time point if the patient comes off study for disease progression before week 12. Coefficients are on a continuous scale ranging from -1 to +1 with a value of -1 indicating a perfect negative linear association of testosterone levels between the 2 time points, a value of 0 indicating no association between testosterone levels between the two time points, and a value of +1 indicating a positive linear association of testosterone levels between the two time points. | Baseline and Week 12 | |
Secondary | Comparison of Circulating Testosterone Levels Between Primary-Resistant Patients and Responders | The distribution of the baseline testosterone levels and the change in hormone level at 12 weeks will be compared between patients experiencing a PSA decline >30% (responders) and patients without such a PSA decline (primary-resistant) using a two group t statistic. Measurements will be obtained at an earlier time point if the patient comes off study for disease progression before week 12. | Baseline and Week 12 | |
Secondary | Correlation of Circulating Dehydroepiandrosterone (DHEA) Levels From Baseline to Week 12 | Pearson's correlation coefficients ("r") will be calculated to summarize the relationship between DHEA values at baseline and at 12 weeks. DHEA labs will be obtained at an earlier time point if the patient comes off study for disease progression before week 12. Coefficients are on a continuous scale ranging from -1 to +1 with a value of -1 indicating a perfect negative linear association of DHEA levels between the 2 time points, a value of 0 indicating no association between DHEA levels between the two time points, and a value of +1 indicating a positive linear association of DHEA levels between the two time points. | Baseline and Week 12 | |
Secondary | Comparison of Circulating DHEA Levels Between Primary-Resistant and Responders | The distribution of the baseline DHEA levels and the change in hormone level at 12 weeks will be compared between patients experiencing a PSA decline >30% (responders) and patients without such a PSA decline (primary-resistant) using a two group t statistic. Measurements will be obtained at an earlier time point if the patient comes off study for disease progression before week 12. | Baseline and Week 12 | |
Secondary | Correlation of Circulating Dehydroepiandrosterone-sulfate (DHEA-S) Levels at Baseline and Week 12 | Pearson's correlation coefficients ("r") will be calculated to summarize the relationship between DHEA-S values at baseline and at 12 weeks. DHEA-S labs will be obtained at an earlier time point if the patient comes off study for disease progression before week 12. Coefficients are on a continuous scale ranging from -1 to +1 with a value of -1 indicating a perfect negative linear association of DHEA-S levels between the 2 time points, a value of 0 indicating no association between DHEA-S levels between the two time points, and a value of +1 indicating a positive linear association of DHEA-S levels between the two time points. | Baseline and Week 12 | |
Secondary | Comparison of Circulating DHEA-S Levels Between Primary-Resistant Patients and Responders | The distribution of the baseline DHEA-S levels and the change in hormone level at 12 weeks will be compared between patients experiencing a PSA decline >30% (responders) and patients without such a PSA decline (primary-resistant) using a two group t statistic. Measurements will be obtained at an earlier time point if the patient comes off study for disease progression before week 12. | Baseline and Week 12 | |
Secondary | Correlation of Circulating Androstenedione Levels at Baseline and Week 12 | Pearson's correlation coefficients ("r") will be calculated to summarize the relationship between androstenedione values at baseline and at 12 weeks. Androstenedione labs will be obtained at an earlier time point if the patient comes off study for disease progression before week 12. Coefficients are on a continuous scale ranging from -1 to +1 with a value of -1 indicating a perfect negative linear association of androstenedione levels between the 2 time points, a value of 0 indicating no association between androstenedione levels between the two time points, and a value of +1 indicating a positive linear association of androstenedione levels between the two time points. | Baseline and Week 12 | |
Secondary | Comparison of Circulating Androstenedione Levels Between Primary-Resistant Patients and Responders | The distribution of the baseline androstenedione levels and the change in hormone level at 12 weeks will be compared between patients experiencing a PSA decline >30% (responders) and patients without such a PSA decline (primary-resistant) using a two group t statistic. Measurements will be obtained at an earlier time point if the patient comes off study for disease progression before week 12. | Baseline and Week 12 |
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