RAD1: Abiraterone Prednisone and Hormonal Therapy Before and During Radiation Therapy in Localized Prostate Cancer

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT01023061
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 24
• Locations: 2
• Arm: 1
• Duration (Months): 66
• Patients Per Site: 12
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial studies the side effects and how well abiraterone acetate, prednisone, and leuprolide acetate or goserelin before and during radiation therapy works in treating patients with localized or locally advanced prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as abiraterone acetate, leuprolide acetate, and goserelin, may lessen the amount of androgens made by the body. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving abiraterone acetate and leuprolide acetate or goserelin before or together with radiation therapy may be an effective treatment for prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Prostate; Stage II Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer	Drug: abiraterone acetate; Drug: prednisone; Drug: leuprolide acetate; Other: laboratory biomarker analysis; Radiation: external beam radiation therapy; Drug: goserelin acetate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate the safety of abiraterone (abiraterone acetate) and prednisone with luteinizing hormone-releasing hormone agonist given as neoadjuvant and concurrent therapy with external beam radiation in patients with localized prostate cancer.

2. To determine whether pharmacologic suppression of the prostatic androgen axis by inhibition of androgen production with abiraterone can decrease tissue androgen levels to below those observed with gonadotropin-releasing hormone (GnRH) agonist suppression of testicular androgens.

SECONDARY OBJECTIVES:

1. To determine whether treatment with abiraterone acetate with luteinizing releasing hormone agonist will be more effective than agonist with bicalutamide in inducing inhibition of androgen-regulated gene expression and increased apoptotic cell death as assessed by immunohistochemistry, complementary deoxyribonucleic acid (cDNA) microarray analysis and reverse transcription-polymerase chain reaction (RT-PCR).

2. To evaluate time to prostate-specific antigen progression in patients treated with GnRH agonist with abiraterone acetate.

OUTLINE:

Patients receive abiraterone acetate orally and prednisone once daily for 24 weeks. Patients also receive leuprolide acetate or goserelin in weeks 1 and 13. Patients undergo external beam radiotherapy starting in week 15 for 8.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Radiation With Androgen Deprivation: Abiraterone Acetate, Prednisone and Luteinizing Hormone Releasing Hormone Agonist Prior to Radiation Therapy
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (antihormone therapy and radiation therapy) Patients receive abiraterone acetate and prednisone daily for 24 weeks. Patients also receive leuprolide acetate or goserelin in weeks 1 and 13. Patients undergo external beam radiotherapy starting in week 15 for 8.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.	Drug: abiraterone acetate; Given PO; Other Names: Zytiga ; Drug: prednisone; Given PO; Other Names: DeCortin Deltra ; Drug: leuprolide acetate; Given via injection; Other Names: Enantone Lupron Lupron Depot ; Other: laboratory biomarker analysis; Correlative study; Radiation: external beam radiation therapy; Undergo radiotherapy; Drug: goserelin acetate; Given via injection; Other Names: Zoladex

Outcome Measures

Primary Outcome Measures

1. Incidence of Acute and Chronic Grade 3 or Greater Toxicity as Evaluated Using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 [Up to 24 months after initiation of radiation therapy]

   Incidence of acute and chronic grade 3 or greater toxicity as evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0he distribution of time to late adverse events (observed severities of adverse events over time) will be estimated using the Kaplan-Meier method.

2. Levels of Dihydrotestosterone (DHT) and Testosterone in Prostate Biopsy Sample Assessed by Mass Spectrometry [Week 12]

   The levels from patients treated in this study will be compared to a control set of biopsies acquired from a separate but similar population of men with intermediate and high risk prostate cancer treated with three months of combined Luteinizing hormone releasing hormone agonist and bicalutamide as part of standard of care.

Secondary Outcome Measures

1. Median Time to Prostate Specific Antigen Progression [6 months]

   Defined as the date of an increase of 2ng/mL or more above the Prostate specific antigen nadir achieved after completion of radiation with the date of progression defined as the date on which that value was measured. Distribution of time-to-event variables will be estimated using the Kaplan-Meier product-limit method. Estimated with two-sided 95% confidence intervals.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Willing and able to provide written informed consent

• Patients must allow biopsy prior to neoadjuvant therapy and at the time of fiducial placement

• Written Authorization for Use and Release of Health and Research Study Information has been obtained

• Histologically proven adenocarcinoma of the prostate

• Patients must be candidates for short or long term androgen deprivation in combination with external beam radiotherapy (RT) based on the following criteria:

• Intermediate Risk Disease: T2b/c, or Gleason 7, or Prostate Specific Antigen 10-20

• High Risk Disease: Gleason 8-10, or Prostate specific antigen> 20, or T3/4

• Patients may not have received any prior pharmacologic therapy or radiation therapy (RT) for prostate cancer

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Karnofsky >= 60%

• Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the androgen axis will be determined following review of their case by the Principal Investigator

• White blood cell count: >= 3,000/mm^3

• Absolute granulocyte count: >= 1,000/mm^3

• Platelets: >= 100,000/mm^3

• Hemoglobin >= 10g/dL

• Potassium >= 3.5 mmol/L

• Serum creatinine: =< 1.5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST) < 2.5 x ULN

• Alanine transaminase (ALT) < 2.5 x ULN

• Total bilirubin: =< 1.5 x ULN (except for patients with documented Gilbert's disease)

Exclusion Criteria:

• Patients may not be receiving any investigational agents

• Concurrent enrollment in another clinical investigational drug or device study is prohibited

• The concurrent administration of other anticancer therapy, including cytotoxic or hormonal agents (except Luteinizing hormone releasing hormone agonists), or immunotherapy, is prohibited during neoadjuvant concurrent and adjuvant therapy

• Patients who are currently receiving active therapy for other neoplastic disorders will not be eligible

• Patients with histologic evidence of small cell carcinoma of the prostate will not be eligible

• Patients with hypogonadism or severe androgen deficiency as defined by serum testosterone less than 100 ng/dL will not be eligible

• History of pituitary or adrenal dysfunction

• Patients who are receiving any androgens, estrogens or progestational agents, or who received any of these agents within the 6 months prior to evaluation will not be eligible

• Patients who are taking drugs which affect androgen metabolism (e.g. spironolactone, ketoconazole, finasteride, dutasteride) will not be eligible

• Concomitant therapy with any of the following listed is prohibited: 5 alpha-reductase inhibitor (finasteride, dutasteride); ketoconazole, diethylstilbestrol, and other preparations such as saw palmetto thought to have endocrine effects on prostate cancer; radiopharmaceuticals such as strontium (89Sr) or samarium (153Sm); Aldactone, Spironol (spironolactone); estrogens, testosterone, progesterones, herbal medications

• Patients who received any of these agents within the 6 months prior to evaluation will be reviewed for eligibility by the Principal Investigator on a case by case basis

• Use of other investigational drug therapy for any reason is prohibited

• Patients with inflammatory bowel disease or other autoimmune conditions which might affect the radiated colon or rectum

• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia which is symptomatic or requires active therapy, recent deep venous thrombosis, pulmonary emboli, cerebrovascular accident or ischemia will not be eligible

• Patients who have chronic active hepatitis or acute hepatitis will not be eligible

• Patients with dementia/psychiatric illness/social situations that would limit compliance with study requirements or would prohibit the understanding and/or giving of informed consent will not be eligible

• Patients with medical conditions, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained will not be eligible

• Uncontrolled hypertension within the screening period (systolic blood pressure [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 congestive heart failure of any severity

• Other active malignancy, except non-melanoma skin cancer and superficial bladder cancer

• History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug

• Patients with diabetes not controlled with diet alone (i.e. requiring insulin or oral hypoglycemics)

• Patients unwilling to use contraceptives while on study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
2	MultiCare Regional Cancer Center - Tacoma	Tacoma	Washington	United States	98405

Sponsors and Collaborators

• University of Washington
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Robert Montgomery, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

• Cho E, Mostaghel EA, Russell KJ, Liao JJ, Konodi MA, Kurland BF, Marck BT, Matsumoto AM, Dalkin BL, Montgomery RB. External beam radiation therapy and abiraterone in men with localized prostate cancer: safety and effect on tissue androgens. Int J Radiat Oncol Biol Phys. 2015 Jun 1;92(2):236-43. doi: 10.1016/j.ijrobp.2015.01.020. Epub 2015 Mar 12.

• Responsible Party: Bruce Montgomery, Principal Investigator, University of Washington
• ClinicalTrials.gov Identifier: NCT01023061
• Other Study ID Numbers: 7048; NCI-2009-01346; 7048 - AbiRAD; 7048; P30CA015704
• First Posted: Dec 2, 2009
• Last Update Posted: Jun 6, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Prostatic Neoplasms; Prednisone; Leuprolide; Goserelin; Abiraterone Acetate

Study Results

Participant Flow

Arm/Group Title	Treatment (Antihormone Therapy and Radiation Therapy)
Arm/Group Description	Patients receive abiraterone acetate and prednisone daily for 24 weeks. Patients also receive leuprolide acetate or goserelin in weeks 1 and 13. Patients undergo external beam radiotherapy starting in week 15 for 8.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. abiraterone acetate: Given orally prednisone: Given orally leuprolide acetate: Given via injection laboratory biomarker analysis: Correlative study external beam radiation therapy: Undergo radiotherapy goserelin acetate: Given via injection
Period Title: Overall Study
STARTED	24
COMPLETED	22
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Treatment (Antihormone Therapy and Radiation Therapy)
Arm/Group Description	Patients receive abiraterone acetate and prednisone for 24 weeks. Patients also receive leuprolide acetate or goserelin in weeks 1 and 13. Patients undergo external beam radiotherapy starting in week 15 for 8.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. abiraterone acetate: Given orally prednisone: Given orally leuprolide acetate: Given via injection laboratory biomarker analysis: Correlative study external beam radiation therapy: Undergo radiotherapy goserelin acetate: Given via injection
Overall Participants	24
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	61 (9.1)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	24 100%
Region of Enrollment (participants) [Number]
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of Acute and Chronic Grade 3 or Greater Toxicity as Evaluated Using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0
Description	Incidence of acute and chronic grade 3 or greater toxicity as evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0he distribution of time to late adverse events (observed severities of adverse events over time) will be estimated using the Kaplan-Meier method.
Time Frame	Up to 24 months after initiation of radiation therapy

Outcome Measure Data

Analysis Population Description

Treated patients

Arm/Group Title	Treatment (Antihormone Therapy and Radiation Therapy)
Arm/Group Description	Patients receive abiraterone acetate PO and prednisone PO for 24 weeks. Patients also receive leuprolide acetate or goserelin in weeks 1 and 13. Patients undergo external beam radiotherapy starting in week 15 for 8.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. abiraterone acetate: Given PO prednisone: Given PO leuprolide acetate: Given via injection laboratory biomarker analysis: Correlative study external beam radiation therapy: Undergo radiotherapy goserelin acetate: Given via injection
Measure Participants	22
Count of Participants [Participants]	6 25%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Antihormone Therapy and Radiation Therapy)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.01
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Levels of Dihydrotestosterone (DHT) and Testosterone in Prostate Biopsy Sample Assessed by Mass Spectrometry
Description	The levels from patients treated in this study will be compared to a control set of biopsies acquired from a separate but similar population of men with intermediate and high risk prostate cancer treated with three months of combined Luteinizing hormone releasing hormone agonist and bicalutamide as part of standard of care.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Treated patients with measurable tissue DHT

Arm/Group Title	Treatment (Antihormone Therapy and Radiation Therapy)
Arm/Group Description	Patients receive abiraterone acetate PO and prednisone PO for 24 weeks. Patients also receive leuprolide acetate or goserelin in weeks 1 and 13. Patients undergo external beam radiotherapy starting in week 15 for 8.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. abiraterone acetate: Given PO prednisone: Given PO leuprolide acetate: Given via injection laboratory biomarker analysis: Correlative study external beam radiation therapy: Undergo radiotherapy goserelin acetate: Given via injection
Measure Participants	22
Median (90% Confidence Interval) [pg/mg]	0.050

3. Secondary Outcome

Title	Median Time to Prostate Specific Antigen Progression
Description	Defined as the date of an increase of 2ng/mL or more above the Prostate specific antigen nadir achieved after completion of radiation with the date of progression defined as the date on which that value was measured. Distribution of time-to-event variables will be estimated using the Kaplan-Meier product-limit method. Estimated with two-sided 95% confidence intervals.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Treated patients

Arm/Group Title	Treatment (Antihormone Therapy and Radiation Therapy)
Arm/Group Description	Patients receive abiraterone acetate PO and prednisone PO for 24 weeks. Patients also receive leuprolide acetate or goserelin in weeks 1 and 13. Patients undergo external beam radiotherapy starting in week 15 for 8.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. abiraterone acetate: Given PO prednisone: Given PO leuprolide acetate: Given via injection laboratory biomarker analysis: Correlative study external beam radiation therapy: Undergo radiotherapy goserelin acetate: Given via injection
Measure Participants	22
Mean (Standard Deviation) [years]	5 (1)

Adverse Events

Time Frame	Median follow-up 21 months
Adverse Event Reporting Description	Tracked grade 1 and 2 toxicities >10% and grade 3 toxicities that were either possibly or probably related to radiation, abiraterone or prednisone, or Luteinizing hormone releasing hormone agonist.
Arm/Group Title	Treatment (Antihormone Therapy and Radiation Therapy)
Arm/Group Description	Patients receive abiraterone acetate and prednisone for 24 weeks. Patients also receive leuprolide acetate or goserelin in weeks 1 and 13. Patients undergo external beam radiotherapy starting in week 15 for 8.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. abiraterone acetate: Given orally prednisone: Given orally leuprolide acetate: Given via injection laboratory biomarker analysis: Correlative study external beam radiation therapy: Undergo radiotherapy goserelin acetate: Given via injection
All Cause Mortality
	Treatment (Antihormone Therapy and Radiation Therapy)
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Serious Adverse Events
	Treatment (Antihormone Therapy and Radiation Therapy)
	Affected / at Risk (%)	# Events
Total	0/22 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Antihormone Therapy and Radiation Therapy)
	Affected / at Risk (%)	# Events
Total	19/22 (86.4%)
Blood and lymphatic system disorders
Lymphopenia	19/22 (86.4%)	19
Cardiac disorders
Hypertension	8/22 (36.4%)	8
Gastrointestinal disorders
Diarrhea	9/22 (40.9%)	9
General disorders
fatigue	15/22 (68.2%)	15
insomnia	3/22 (13.6%)	3
Hepatobiliary disorders
Hyperbilirubinemia	5/22 (22.7%)	5
Investigations
hypokalemia syndrome	12/22 (54.5%)	12
Metabolism and nutrition disorders
ALT and AST: increased	7/22 (31.8%)	7
Renal and urinary disorders
urinary tract discomfort	19/22 (86.4%)	19
Reproductive system and breast disorders
erectile dysfunction	7/22 (31.8%)	7
Vascular disorders
Hot flashes	15/22 (68.2%)	15

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.