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Enzalutamide, Radiation Therapy and Hormone Therapy in Treating Patients With Intermediate or High-Risk Prostate Cancer

Primary Purpose

Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage IIB Prostate Cancer

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Enzalutamide

Goserelin acetate

Leuprolide acetate

Radiation therapy

About this trial

This is an interventional treatment trial for Adenocarcinoma of the Prostate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Prostate adenocarcinoma without distant metastatic disease with either Gleason score ≥ 7, PSA ≥ 10 ng/ml, or T2b or greater disease
Age > 18
Performance Status: ECOG 0-1
Hematologic (minimal values):
- Absolute neutrophil count > 1,500/mm3
- Hemoglobin > 8.0 g/dl
- Platelet count > 100,000/mm3
Hepatic function
- Total bilirubin < Upper limit of normal (ULN)(except for Gilbert's disease)
- AST (SGOT) < 1.5 x ULN
- ALT (SGPT) < 1.5 x ULN
Creatinine < 1.5 x ULN
Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.

Exclusion Criteria:

Patients with a history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold
History of urological surgery or procedures predisposing to GU complications after radiation (will be determined by radiation oncologist)
History of diverticulitis, rectal bleeding or other lower GI diseases predisposing to GI complications after radiation (will be determined by radiation oncologist)
History of prior chemotherapy or pelvic irradiation,
History of prior invasive malignant cancer(s) within the last 5 years except adequately treated or controlled basal cell or squamous cell carcinoma of the skin.
Documented distant metastatic disease. NOTE: pelvic lymphadenopathy is NOT excluded.
Prior radical prostatectomy or cryosurgery for prostate cancer or bilateral orchiectomy.
No experimental medications within 30 days of study entry
Patients currently taking the following medications:
- CYP2C8 inhibitors (e.g. Gemfibrozil)
- CYP2C8 inducers (e.g. rifampin)
- CYP3A4 inhibitors (itraconazole)
- CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine)

Sites / Locations

Thomas Jefferson University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (enzalutamide, radiation therapy, hormone therapy)

Arm Description

Patients receive enzalutamide PO QD for 6 months. Beginning 2 weeks after start of enzalutamide, patients receive LHRH agonist therapy with goserelin acetate SC or leuprolide acetate IM or SC for 6 months (intermediate risk patients) or 24 months (high risk patients) post-radiation therapy. Beginning 8 weeks after the start of LHRH therapy, patients undergo either IMRT or VMAT daily five days a week for 8 weeks.

Outcomes

Primary Outcome Measures

Acute toxicities, monitored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 criteria

An exact 2-sided binomial 90% confidence interval will be computed and reported. Toxicity will be monitored and if there is greater than 10% incidence of grade 3 or higher gastrointestinal (GI)/genitourinary (GU)/fatigue lasting more than 7 days despite optimal treatment, the trial will be re-evaluated.

Secondary Outcome Measures

Change in PSA levels

Evaluated using linear mixed models. Mixed models will make use of all available data, and can estimate individual levels of change.

Quality of life (QoL), measured using the EPIC, AUA symptom index, and the PROMIS Fatigue Scale

QoL measures will also be assessed via linear mixed models, as an exploratory evaluation of potential clinical correlates, such as age, race, stage, Gleason score, etc.

Full Information

NCT ID

NCT02023463

First Posted

December 23, 2013

Last Updated

October 6, 2023

Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

Collaborators

Astellas Pharma Inc, Medivation, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02023463

Brief Title

Enzalutamide, Radiation Therapy and Hormone Therapy in Treating Patients With Intermediate or High-Risk Prostate Cancer

Official Title

Phase Ib Trial of Enzalutamide in Combination With Radiation Therapy and LHRH Agonist Therapy in the Management of Intermediate and High-Risk Prostate Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

April 2, 2014 (Actual)

Primary Completion Date

July 10, 2017 (Actual)

Study Completion Date

January 1, 2040 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

Collaborators

Astellas Pharma Inc, Medivation, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This phase I trial studies the side effects and best way to give enzalutamide, radiation therapy, and hormone therapy in treating patients with intermediate or high-risk prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as enzalutamide, may lessen the amount of androgens made by the body. Radiation therapy uses high energy x rays to kill tumor cells. Giving enzalutamide, radiation therapy, and hormone therapy may be an effective treatment for prostate cancer.

Detailed Description

PRIMARY OBJECTIVE: 1) To assess the safety of the combination of neoadjuvant and concurrent enzalutamide with an luteinizing-hormone-releasing hormone (LHRH) agonist and radiation therapy. SECONDARY OBJECTIVES: To determine the efficacy of the combination of enzalutamide with an LHRH agonist and radiation therapy using prostate specific antigen (PSA) kinetics. To determine the efficacy of the combination of enzalutamide with an LHRH agonist and radiation therapy using PSA nadir. To describe patient-reported outcomes including: Expanded Prostate Cancer Index Composite (EPIC), American Urological Association (AUA) Symptom Index, PROstate magnetic resonance (MR) Imaging Study (PROMIS) Fatigue Scale. OUTLINE: Patients receive enzalutamide orally (PO) once daily (QD) for 6 months. Beginning 2 weeks after start of enzalutamide, patients receive LHRH agonist therapy with goserelin acetate subcutaneously (SC) or leuprolide acetate intramuscularly (IM) or SC for 6 months (intermediate risk patients) or 24 months (high risk patients) post-radiation therapy. Beginning 8 weeks after the start of LHRH agonist therapy, patients undergo either intensity modulated radiation therapy (IMRT) or volumetric arc therapy (VMAT) daily five days a week for 8 weeks. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer, Stage IV Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (enzalutamide, radiation therapy, hormone therapy)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Enzalutamide

Other Intervention Name(s)

Xtandi, MDV3100

Intervention Description

Given PO

Intervention Type

Drug

Intervention Name(s)

Goserelin acetate

Other Intervention Name(s)

Goserelin, Zoladex

Intervention Description

Given SC

Intervention Type

Drug

Intervention Name(s)

Leuprolide acetate

Other Intervention Name(s)

Leuprorelin, Leuprolide

Intervention Description

Given IM or SC

Intervention Type

Radiation

Intervention Name(s)

Radiation therapy

Other Intervention Name(s)

irradiation, radiotherapy, therapy, radiation

Intervention Description

Undergo image-guided radiation therapy

Primary Outcome Measure Information:

Title

Acute toxicities, monitored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 criteria

Description

Time Frame

Up to 1 month post completion of enzalutamide

Secondary Outcome Measure Information:

Title

Change in PSA levels

Description

Evaluated using linear mixed models. Mixed models will make use of all available data, and can estimate individual levels of change.

Time Frame

Baseline up to 6 months

Title

Quality of life (QoL), measured using the EPIC, AUA symptom index, and the PROMIS Fatigue Scale

Description

QoL measures will also be assessed via linear mixed models, as an exploratory evaluation of potential clinical correlates, such as age, race, stage, Gleason score, etc.

Time Frame

Baseline up to 1 year

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Prostate adenocarcinoma without distant metastatic disease with either Gleason score ≥ 7, PSA ≥ 10 ng/ml, or T2b or greater disease Age > 18 Performance Status: ECOG 0-1 Hematologic (minimal values): Absolute neutrophil count > 1,500/mm3 Hemoglobin > 8.0 g/dl Platelet count > 100,000/mm3 Hepatic function Total bilirubin < Upper limit of normal (ULN)(except for Gilbert's disease) AST (SGOT) < 1.5 x ULN ALT (SGPT) < 1.5 x ULN Creatinine < 1.5 x ULN Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. Exclusion Criteria: Patients with a history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold History of urological surgery or procedures predisposing to GU complications after radiation (will be determined by radiation oncologist) History of diverticulitis, rectal bleeding or other lower GI diseases predisposing to GI complications after radiation (will be determined by radiation oncologist) History of prior chemotherapy or pelvic irradiation, History of prior invasive malignant cancer(s) within the last 5 years except adequately treated or controlled basal cell or squamous cell carcinoma of the skin. Documented distant metastatic disease. NOTE: pelvic lymphadenopathy is NOT excluded. Prior radical prostatectomy or cryosurgery for prostate cancer or bilateral orchiectomy. No experimental medications within 30 days of study entry Patients currently taking the following medications: CYP2C8 inhibitors (e.g. Gemfibrozil) CYP2C8 inducers (e.g. rifampin) CYP3A4 inhibitors (itraconazole) CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert Den, MD

Organizational Affiliation

Thomas Jefferson University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Thomas Jefferson University

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.JeffersonHospital.org

Description

Thomas Jefferson University Hospitals

Learn more about this trial

Enzalutamide, Radiation Therapy and Hormone Therapy in Treating Patients With Intermediate or High-Risk Prostate Cancer

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