search
Back to results

EXTEND Exercise Trial

Primary Purpose

Non-metastatic, Hormone naïve Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Enzalutamide
Androgen deprivation therapy
Supervised exercise training
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-metastatic, Hormone naïve Prostate Cancer

Eligibility Criteria

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

Inclusion Criteria:

  1. Male age ≥ 18 years.
  2. Histologically-confirmed adenocarcinoma of the prostate.
  3. Completion of appropriate prior treatment with local therapy (i.e., prostatectomy, radiation therapy or equivalent), per NCCN Guidelines.
  4. Detectable PSA, defined as PSA ≥0.01 ng/ml
  5. Appropriate for treatment with ADT in the opinion of the treating physician.
  6. Serum total testosterone ≥150 ng/dL (5.2 nmol/L).
  7. ECOG performance status of ≤ 1 (Appendix A)
  8. Planned treatment with castration therapy (GnRH agonist/antagonist) for ≥8 months.
  9. Must not have any of the following absolute contraindications to cardiopulmonary exercise testing and/or aerobic training as determined by the attending oncologist:

    Absolute Contraindications

    • Acute myocardial Infarction (within 3-5 days of any planned study procedures)
    • Unstable angina
    • Uncontrolled arrhythmia causing symptoms or hemodynamic compromise
    • Recurrent syncope
    • Active endocarditis
    • Acute myocarditis or pericarditis
    • Symptomatic severe aortic stenosis
    • Uncontrolled heart failure
    • Acute (within 3 months) pulmonary embolus or pulmonary infarction
    • Thrombosis of lower extremities
    • Suspected dissecting aneurysm
    • Uncontrolled asthma
    • Pulmonary edema
    • Room air desaturation at rest <85%
    • Respiratory failure
    • Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e. infection, renal failure, thyrotoxicosis)
    • Mental impairment leading to inability to cooperate.
  10. Able to swallow enzalutamide and comply with study requirements.
  11. Must be able to complete an acceptable cardiopulmonary exercise test (CPET) at baseline (see Section 9), defined as at least one of the following:

    • Achieving a plateau in oxygen consumption concurrent with an increase in power output;
    • Respiratory exchange ratio ≥ 1.1 (RER);
    • Volitional exhaustion with a rating of perceived exertion ≥ 17 (RPE)
  12. Must be able to complete an acceptable muscular strength test (assessed using calculated one-repetition maximum (1-RM)) at baseline (see Section 9), in the opinion of the fitness specialist, exercise physiologist, or trained designee administering the test.
  13. Life expectancy of ≥ 12 months.
  14. Must use a condom if having sex with a pregnant woman.
  15. Male subject and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration. Two acceptable methods of birth control thus include the following:

    • Condom (barrier method of contraception); AND

    One of the following is required:

    • Established use of oral, or injected or implanted hormonal method of contraception by the female partner;
    • Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner;
    • Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner;
    • Tubal ligation in the female partner;
    • Vasectomy or other procedure resulting in infertility (e.g., bilateral orchiectomy), for more than 6 months
  16. Subjects must have normal organ and marrow function as defined below:

    • absolute neutrophil count >1,500/µL
    • platelets >100,000/µL
    • total bilirubin <2.5 X institutional upper limit of normal
    • AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal
    • Creatinine ≤ 2.0 OR creatinine clearance >30 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.

Exclusion Criteria:

  1. Definite evidence of metastatic prostate cancer, in the opinion of the treating physician. Pelvic and retroperitoneal lymph nodes < 2.0 cm in short axis are allowed.
  2. Subjects who have had treatments with GnRH agonists/antagonists and/or anti-androgens within 1 year of randomization.
  3. Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA values (e.g., saw palmetto) or systemic corticosteroids for prostate cancer within 4 weeks of day 29 visit (start of Enzalutamide and ADT).
  4. Subjects who have had radiotherapy within 12 weeks prior to entering the study or those who have not recovered from adverse events due to agents or therapies administered for treatment of prostate cancer more than 4 weeks earlier (except urinary, rectal, and sexual side effects related to prostatectomy or radiotherapy are permitted)
  5. Subjects who have had any surgical procedure (i.e. TURP, etc.) within 4 weeks prior to entering the study.
  6. Subjects who are receiving any other investigational agents.
  7. Significant cardiovascular disease, including:

    • Symptomatic left ventricular dysfunction or known baseline left ventricular ejection fraction (LVEF) by multigated acquisition scan (MUGA) or echocardiogram (ECHO) of < lower limit of institutional normal (LLN). "Symptomatic" is defined as New York Heart Association (NYHA) Class II or greater. Note: MUGA and ECHCO do NOT need to be measured to establish eligibility for this study.
    • Uncontrolled hypertension (in the opinion of the treating provider).
    • Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug.
    • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) within 12 months of first dose of study drug.
    • Uncontrolled cardiac arrhythmias.
    • Coronary or peripheral artery bypass graft within 6 months of first dose of study drug.
    • History of CVA, TIA, or rest claudication within 6 months of first dose of study drug.
  8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements (in the opinion of the treating provider).
  9. Subjects with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs the ability to swallow and retain enzalutamide are excluded.
  10. History of another invasive cancer within 5 years of randomization with the exceptions of (a) non-melanoma skin cancers and (b) American Joint Committee on Cancer (AJCC) Stage 0 or 1 cancers that have a remote probability of recurrence, in the opinion of the treating physician, in consultation with the principal investigator.
  11. Known or suspected brain metastasis or leptomeningeal disease.
  12. History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past. Also, history of loss of consciousness or transient ischemic attack within 12 months of the Day 1 visit.

Sites / Locations

  • Memorial Sloan Kettering Cancer Center
  • Duke University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

ENZ+ADT+Usual care

ENZ+ADT+Exercise

Arm Description

The usual care arm will receive treatment with enzalutamide with androgen deprivation therapy, with no supervised exercise training.

The ENZ+ADT+Exercise arm will receive treatment with enzalutamide plus androgen deprivation therapy along with supervised exercise training.

Outcomes

Primary Outcome Measures

Change in VO2peak in Usual Care Versus Exercise Training Arms
Mean change in peak oxygen uptake (VO2peak) from week 1 to week 17 in the usual care and exercise training groups

Secondary Outcome Measures

17-week Change in Functional Capacity as Measured by Chair-stand Test
Mean change in number of seconds to perform the chair-stand test between baseline and week 17. This test measures the time taken to complete 5 repetitions of the sit-to-stand maneuver from a chair without an arm rest at 43 cm in height and 47.5 cm in depth. This test provides an indicator of functional performance of lower body strength; quicker times indicate greater strength
17-week Change in Upper and Lower Extremity Maximal Muscular Strength
Mean change in upper and lower extremity maximal muscular strength as measured by the voluntary one-repetition max (1-RM) and muscular endurance as measured by 70% of 1-RM between week 17 and baseline
Effects on Serum Glucose
Mean change in fasting serum glucose between week 17 and baseline.
Change in the Effect on Patient Reported Outcomes (PROs) of Interest Over Time
Mean change in PROs aggregate score between week 17 and baseline. PROs include the FACT-Prostate (FACT-P, range 0 to 104), FACIT-Fatigue (FACIT-F, range 0 to 52), and the Godin Leisure Questionnaire. Higher scores indicate better quality of life.
Eligibility Rate
Eligibility rate is defined as the number of subjects found to be eligible divided by the number approached for the study. Note that ineligible subjects are not randomized. This is reported as a percent.
Acceptance Rate
Acceptance rate is defined as the number of patients agreeing to participate divided by total number randomized. This is reported as a percent.
Adherence Rate
Adherence rate is defined as the percentage of days that each patient fulfilled the assigned exercise prescription of the 48 days. The median percentage is reported.
Attrition Rate
Attrition rate is defined as the percent of subjects who complete the 16 week exercise training program. This outcome applies only to the exercise arm.
17-week Change in Functional Capacity as Measured by Time Up and Go Test
Mean change in number of seconds to complete the timed up and go test between week 17 and baseline. This test requires patients to stand up from a chair with armrests, walk 3m, turn around, return to the chair, and sit down
17-week Change in Functional Capacity as Measured by Six Minute Walk Test
Mean change in distance covered during the six minute walk test between week 17 and baseline. This test requires patients to cover the longest distance possible in six minutes under the supervision of an exercise physiologist or designee.
17-week Change in Muscle Cross-sectional Area (CSA)
Mean change in muscle cross sectional area of the dominant quadricep, hamstring, and total mid-thigh between week 17 and baseline. Cross-sectional area was measured using magnetic resonance imaging with a 3.0T-scanner.
Effects on Serum Insulin
Mean change in fasting serum insulin between week 17 and baseline.
Effects on Blood Hemoglobin (Hgb)
Mean change in blood hemoglobin (Hgb) A1C between week 17 and baseline.
Effects on Body Composition
Mean change in lean body mass and fat body mass between week 17 and baseline as measured by a DEXA Scan.

Full Information

First Posted
August 22, 2014
Last Updated
March 28, 2019
Sponsor
Duke University
search

1. Study Identification

Unique Protocol Identification Number
NCT02256111
Brief Title
EXTEND Exercise Trial
Official Title
EXTEND: Safety and Efficacy of EXercise Training in Men Receiving ENzalutamide in Combination With Conventional Androgen Deprivation Therapy for Hormone Naïve Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
May 13, 2015 (Actual)
Primary Completion Date
February 21, 2018 (Actual)
Study Completion Date
July 17, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will examine the effect of supervised exercise training on cardiopulmonary function in men receiving the combination of enzalutamide (ENZ) and androgen deprivation therapy (ADT) for treatment of non-metastatic, hormone-naïve prostate cancer. No study to date has examined the efficacy, tolerability, and safety of exercise training to prevent and/or mitigate common adverse toxicities in men receiving combination androgen suppression therapy for hormone-naïve prostate cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-metastatic, Hormone naïve Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ENZ+ADT+Usual care
Arm Type
Experimental
Arm Description
The usual care arm will receive treatment with enzalutamide with androgen deprivation therapy, with no supervised exercise training.
Arm Title
ENZ+ADT+Exercise
Arm Type
Experimental
Arm Description
The ENZ+ADT+Exercise arm will receive treatment with enzalutamide plus androgen deprivation therapy along with supervised exercise training.
Intervention Type
Drug
Intervention Name(s)
Enzalutamide
Other Intervention Name(s)
Xtandi
Intervention Type
Drug
Intervention Name(s)
Androgen deprivation therapy
Intervention Type
Behavioral
Intervention Name(s)
Supervised exercise training
Primary Outcome Measure Information:
Title
Change in VO2peak in Usual Care Versus Exercise Training Arms
Description
Mean change in peak oxygen uptake (VO2peak) from week 1 to week 17 in the usual care and exercise training groups
Time Frame
From week 1 to week 17
Secondary Outcome Measure Information:
Title
17-week Change in Functional Capacity as Measured by Chair-stand Test
Description
Mean change in number of seconds to perform the chair-stand test between baseline and week 17. This test measures the time taken to complete 5 repetitions of the sit-to-stand maneuver from a chair without an arm rest at 43 cm in height and 47.5 cm in depth. This test provides an indicator of functional performance of lower body strength; quicker times indicate greater strength
Time Frame
Baseline to 17 weeks
Title
17-week Change in Upper and Lower Extremity Maximal Muscular Strength
Description
Mean change in upper and lower extremity maximal muscular strength as measured by the voluntary one-repetition max (1-RM) and muscular endurance as measured by 70% of 1-RM between week 17 and baseline
Time Frame
Baseline to 17 weeks
Title
Effects on Serum Glucose
Description
Mean change in fasting serum glucose between week 17 and baseline.
Time Frame
Baseline to 17 weeks
Title
Change in the Effect on Patient Reported Outcomes (PROs) of Interest Over Time
Description
Mean change in PROs aggregate score between week 17 and baseline. PROs include the FACT-Prostate (FACT-P, range 0 to 104), FACIT-Fatigue (FACIT-F, range 0 to 52), and the Godin Leisure Questionnaire. Higher scores indicate better quality of life.
Time Frame
Baseline to 17 weeks
Title
Eligibility Rate
Description
Eligibility rate is defined as the number of subjects found to be eligible divided by the number approached for the study. Note that ineligible subjects are not randomized. This is reported as a percent.
Time Frame
29 months from study initiation
Title
Acceptance Rate
Description
Acceptance rate is defined as the number of patients agreeing to participate divided by total number randomized. This is reported as a percent.
Time Frame
29 months from study initiation
Title
Adherence Rate
Description
Adherence rate is defined as the percentage of days that each patient fulfilled the assigned exercise prescription of the 48 days. The median percentage is reported.
Time Frame
48 days
Title
Attrition Rate
Description
Attrition rate is defined as the percent of subjects who complete the 16 week exercise training program. This outcome applies only to the exercise arm.
Time Frame
16 weeks
Title
17-week Change in Functional Capacity as Measured by Time Up and Go Test
Description
Mean change in number of seconds to complete the timed up and go test between week 17 and baseline. This test requires patients to stand up from a chair with armrests, walk 3m, turn around, return to the chair, and sit down
Time Frame
Baseline to 17 weeks
Title
17-week Change in Functional Capacity as Measured by Six Minute Walk Test
Description
Mean change in distance covered during the six minute walk test between week 17 and baseline. This test requires patients to cover the longest distance possible in six minutes under the supervision of an exercise physiologist or designee.
Time Frame
Baseline to 17 weeks
Title
17-week Change in Muscle Cross-sectional Area (CSA)
Description
Mean change in muscle cross sectional area of the dominant quadricep, hamstring, and total mid-thigh between week 17 and baseline. Cross-sectional area was measured using magnetic resonance imaging with a 3.0T-scanner.
Time Frame
Baseline to 17 weeks
Title
Effects on Serum Insulin
Description
Mean change in fasting serum insulin between week 17 and baseline.
Time Frame
Baseline to 17 weeks
Title
Effects on Blood Hemoglobin (Hgb)
Description
Mean change in blood hemoglobin (Hgb) A1C between week 17 and baseline.
Time Frame
Baseline to 17 weeks
Title
Effects on Body Composition
Description
Mean change in lean body mass and fat body mass between week 17 and baseline as measured by a DEXA Scan.
Time Frame
Baseline to 17 weeks

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male age ≥ 18 years. Histologically-confirmed adenocarcinoma of the prostate. Completion of appropriate prior treatment with local therapy (i.e., prostatectomy, radiation therapy or equivalent), per NCCN Guidelines. Detectable PSA, defined as PSA ≥0.01 ng/ml Appropriate for treatment with ADT in the opinion of the treating physician. Serum total testosterone ≥150 ng/dL (5.2 nmol/L). ECOG performance status of ≤ 1 (Appendix A) Planned treatment with castration therapy (GnRH agonist/antagonist) for ≥8 months. Must not have any of the following absolute contraindications to cardiopulmonary exercise testing and/or aerobic training as determined by the attending oncologist: Absolute Contraindications Acute myocardial Infarction (within 3-5 days of any planned study procedures) Unstable angina Uncontrolled arrhythmia causing symptoms or hemodynamic compromise Recurrent syncope Active endocarditis Acute myocarditis or pericarditis Symptomatic severe aortic stenosis Uncontrolled heart failure Acute (within 3 months) pulmonary embolus or pulmonary infarction Thrombosis of lower extremities Suspected dissecting aneurysm Uncontrolled asthma Pulmonary edema Room air desaturation at rest <85% Respiratory failure Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e. infection, renal failure, thyrotoxicosis) Mental impairment leading to inability to cooperate. Able to swallow enzalutamide and comply with study requirements. Must be able to complete an acceptable cardiopulmonary exercise test (CPET) at baseline (see Section 9), defined as at least one of the following: Achieving a plateau in oxygen consumption concurrent with an increase in power output; Respiratory exchange ratio ≥ 1.1 (RER); Volitional exhaustion with a rating of perceived exertion ≥ 17 (RPE) Must be able to complete an acceptable muscular strength test (assessed using calculated one-repetition maximum (1-RM)) at baseline (see Section 9), in the opinion of the fitness specialist, exercise physiologist, or trained designee administering the test. Life expectancy of ≥ 12 months. Must use a condom if having sex with a pregnant woman. Male subject and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration. Two acceptable methods of birth control thus include the following: Condom (barrier method of contraception); AND One of the following is required: Established use of oral, or injected or implanted hormonal method of contraception by the female partner; Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner; Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner; Tubal ligation in the female partner; Vasectomy or other procedure resulting in infertility (e.g., bilateral orchiectomy), for more than 6 months Subjects must have normal organ and marrow function as defined below: absolute neutrophil count >1,500/µL platelets >100,000/µL total bilirubin <2.5 X institutional upper limit of normal AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal Creatinine ≤ 2.0 OR creatinine clearance >30 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal. Exclusion Criteria: Definite evidence of metastatic prostate cancer, in the opinion of the treating physician. Pelvic and retroperitoneal lymph nodes < 2.0 cm in short axis are allowed. Subjects who have had treatments with GnRH agonists/antagonists and/or anti-androgens within 1 year of randomization. Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA values (e.g., saw palmetto) or systemic corticosteroids for prostate cancer within 4 weeks of day 29 visit (start of Enzalutamide and ADT). Subjects who have had radiotherapy within 12 weeks prior to entering the study or those who have not recovered from adverse events due to agents or therapies administered for treatment of prostate cancer more than 4 weeks earlier (except urinary, rectal, and sexual side effects related to prostatectomy or radiotherapy are permitted) Subjects who have had any surgical procedure (i.e. TURP, etc.) within 4 weeks prior to entering the study. Subjects who are receiving any other investigational agents. Significant cardiovascular disease, including: Symptomatic left ventricular dysfunction or known baseline left ventricular ejection fraction (LVEF) by multigated acquisition scan (MUGA) or echocardiogram (ECHO) of < lower limit of institutional normal (LLN). "Symptomatic" is defined as New York Heart Association (NYHA) Class II or greater. Note: MUGA and ECHCO do NOT need to be measured to establish eligibility for this study. Uncontrolled hypertension (in the opinion of the treating provider). Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug. History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) within 12 months of first dose of study drug. Uncontrolled cardiac arrhythmias. Coronary or peripheral artery bypass graft within 6 months of first dose of study drug. History of CVA, TIA, or rest claudication within 6 months of first dose of study drug. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements (in the opinion of the treating provider). Subjects with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs the ability to swallow and retain enzalutamide are excluded. History of another invasive cancer within 5 years of randomization with the exceptions of (a) non-melanoma skin cancers and (b) American Joint Committee on Cancer (AJCC) Stage 0 or 1 cancers that have a remote probability of recurrence, in the opinion of the treating physician, in consultation with the principal investigator. Known or suspected brain metastasis or leptomeningeal disease. History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past. Also, history of loss of consciousness or transient ischemic attack within 12 months of the Day 1 visit.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Harrison, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35273377
Citation
Harrison MR, Davis PG, Khouri MG, Bartlett DB, Gupta RT, Armstrong AJ, McNamara MA, Zhang T, Anand M, Onyenwoke K, Edwardson S, Craig D, Michalski M, Wu Y, Oyekunle T, Coyne B, Coburn A, Jones LW, George DJ. A randomized controlled trial comparing changes in fitness with or without supervised exercise in patients initiated on enzalutamide and androgen deprivation therapy for non-metastatic castration-sensitive prostate cancer (EXTEND). Prostate Cancer Prostatic Dis. 2022 Mar;25(1):58-64. doi: 10.1038/s41391-022-00519-4. Epub 2022 Mar 10.
Results Reference
derived

Learn more about this trial

EXTEND Exercise Trial

We'll reach out to this number within 24 hrs