Clinical trial NCT01717053: Abiraterone, Radiotherapy and Short-Term Androgen Deprivation in Unfavorable Localized Prostate Cancer
Official title: A Phase II Trial of Abiraterone Acetate, Radiotherapy and Short-Term Androgen Deprivation in Men With Unfavorable Risk Localized Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Janssen Pharmaceuticals
First posted: 2012-10-30
Enrollment: 37
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The addition of abiraterone acetate to standard treatment of radiotherapy and short-term androgen deprivation will increase the frequency of undetectable PSA.

Detailed description: This is a single arm two-site study of 37 men with unfavorable prostate cancer (defined as having a single high risk factor). Patients will concurrently initiate 6 months of standard-of-care GNRH agonist therapy and once daily abiraterone acetate/prednisone. After 2 months of lead-in hormonal treatment, definitive standard-of-care prostate/seminal vesicle radiotherapy will be delivered, to a total dose of 75-80 Gy.

Eligibility criteria: Inclusion Criteria:

* One of the following high risk criteria:
* Gleason Score 7 with PSA ≤ 20 ng/ml and clinical T1-2, or
* Gleason Score 8-10, PSA ≤ 20 ng/ml and clinical T1-2a, or
* PSA 10.1-40 ng/ml with GS \< 7 and clinical T1-2, or
* Clinical T3 with Gleason Score \< 7 and PSA ≤ 10 ng/ml.
* ECOG Performance Status ≤ 1
* Digital rectal exam within 90 days of registration on study
* CBC with differential with adequate bone marrow function defined as follows:
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3, Platelets \> 100,000/µL and Hemoglobin ≥ 9g/dL
* Serum potassium ≥ 3.5 mEq/L
* Serum albumin \> 3.0 g/dl
* Total bilirubin \< 1.5 X of institutional upper limit of normal (ULN)
* AST(SGOT)/ALT(SGPT) \< 1.5 X ULN
* Calculated creatinine clearance \> 60 mL/min
* Age \> 18 years
* Able to swallow a whole tablet and take abiraterone acetate on an empty stomach (defined as no food for two hours before and one hour after abiraterone acetate ingestion)
* Ability to understand and sign a written informed consent document
* Written authorization for use and release of health and research study information has been obtained
* Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
* Subjects who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protections as determined acceptable by the principal investigator during the study and for 1 week after the last dose of abiraterone acetate.

Exclusion Criteria:

* Bone, visceral or soft tissue metastasis, including lymph nodes (\>2 cm in longest diameter)
* Prior therapy for prostate cancer \[Exceptions: LHRH agonist or antagonist may have been initiated within 30 days prior to enrollment. Bicalutamide may have been given within 60 days of enrollment as long as it has been stopped at least 7 days before enrollment and total duration was no longer than 30 days. This is to allow enrollment of those who have been given bicalutamide as a bridge for LHRH agonist/antagonist. It is highly unlikely a short non-overlapping course of bicalutamide will interact with abiraterone acetate in a measurable way. Previous alpha-reductase inhibitor use allowed IF patient has not been taking for at least 30 days prior to abiraterone acetate initiation, OR if alpha reductase inhibitor was not used as a primary treatment of prostate cancer and the PSA on alpha-reductase inhibitor remains within eligibility when doubled. \]
* Known serum testosterone ≤ 150 ng/dl or symptoms of hypogonadism (fatigue, hot flashes, hair loss, loss of muscle mass, osteoporosis, low libido, depression) prior to ADT initiation not explained by other medical co-morbidity OR history of testosterone supplement. If questionable, serum testosterone level greater than 150 ng/dl can be used to exclude hypogonadism.
* Previous malignancy within 3 years other than non-melanomatous skin cancer and non-muscle invasive bladder cancer
* Previous pelvic radiotherapy that would prevent prostate/SV irradiation
* 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 therapy
* History of gastrointestinal disorders that may interfere with the absorption of study drug (including gastric bypass surgery)
* Concurrent spironolactone use
* Significant concurrent medical condition that would make prednisone/prednisolone use contraindicated or would interfere with the patient's ability to participate in the trial
* Receiving any investigational agents currently or within 30 days prior to study screening
* Prior demonstrated hypersensitivity, intolerance or allergy to abiraterone acetate, prednisone or their excipients
* Active co-morbidity, defined as follows:

  * Chronic liver disease with cirrhosis (Child-Pugh B or C) or active hepatitis B or C
  * History of pituitary or adrenal dysfunction
  * Poorly controlled diabetes mellitus (A1c \>9% or history of complications including peripheral neuropathy, end organ damage, hospitalization, amputation)
  * Poorly controlled glaucoma
  * 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 III-IV heart disease or known cardiac ejection fraction measurement of \< 50% at baseline.
  * Clinical evidence of active infection of any type, including active or symptomatic viral hepatitis.
  * Known immune deficiency and/or HIV-positive patients
  * Any medical condition that warrants long-term corticosteroid use in excess of study dose
* Patients taking strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital)
* Any condition that in the opinion of the Principal Investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing the study requirements

Primary outcomes:
measure: Percentage of Patients With Undetectable PSA (Prostate-Specific Antigen) at 1 Year
timeFrame: 1 year
Secondary outcomes:
measure: Time to PSA Nadir
timeFrame: 1 year
measure: PSA Nadir Value
timeFrame: 1 year, 2 years
measure: Percentage of Participants With Biochemical Progression-free Survival (BPFS)
timeFrame: 36 and 48 months
measure: Metastasis or Systemic Therapy
timeFrame: up to 5 years (60 months)
measure: Testosterone Recovery
timeFrame: up to 5 years
measure: PSA < 1.5ng/ml in Setting of Non-castrate Testosterone
timeFrame: 1 year, 2 years, 3 years, 4 years, 5 years
measure: Safety and Tolerability
timeFrame: 6 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Durham Regional Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Duke University
name: Daniel George, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koontz BF, Hoffman KE, Halabi S, Healy P, Anand M, George DJ, Harrison MR, Zhang T, Berry WR, Corn PG, Lee WR, Armstrong AJ. Combination of Radiation Therapy and Short-Term Androgen Blockade With Abiraterone Acetate Plus Prednisone for Men With High- and Intermediate-Risk Localized Prostate Cancer. Int J Radiat Oncol Biol Phys. 2021 Apr 1;109(5):1271-1278. doi: 10.1016/j.ijrobp.2020.11.059. Epub 2020 Nov 28.