Non-metastatic, Hormone naïve Prostate CancerPhase 2NCT02256111
EXTEND Exercise Trial
A Phase 2 study testing Enzalutamide, Androgen deprivation therapy and Supervised exercise training in people with Non-metastatic, Hormone naïve Prostate Cancer, run by Duke University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Non-metastatic, Hormone naïve Prostate Cancer
- What is being tested?
- Enzalutamide, Androgen deprivation therapy and Supervised exercise training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 May 2015to 17 Jul 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Show all 49Show fewer
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Duke University Medical Center
Durham, North Carolina, 27710
Memorial Sloan Kettering Cancer Center
New York, New York, 10017
About this study
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
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.
- Being tested
- Enzalutamide, Androgen deprivation therapy, Supervised exercise training
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnzalutamideDrug
Also called Xtandi
Androgen deprivation therapyDrug
Supervised exercise trainingBehavioural
| Study group | Role | What they receive |
|---|---|---|
| ENZ+ADT+Usual care | Experimental | The usual care arm will receive treatment with enzalutamide with androgen deprivation therapy, with no supervised exercise training. Receives: Drug: Enzalutamide; Drug: Androgen deprivation therapy |
| ENZ+ADT+Exercise | Experimental | The ENZ+ADT+Exercise arm will receive treatment with enzalutamide plus androgen deprivation therapy along with supervised exercise training. Receives: Drug: Enzalutamide; Drug: Androgen deprivation therapy; Behavioral: Supervised exercise training |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: From week 1 to week 17
Secondary outcomes (14)
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
Measured: Baseline to 17 weeks
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
Measured: Baseline to 17 weeks
Effects on Serum Glucose
Mean change in fasting serum glucose between week 17 and baseline.
Measured: Baseline to 17 weeks
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.
Measured: Baseline to 17 weeks
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.
Measured: 29 months from study initiation
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.
Measured: 29 months from study initiation
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.
Measured: 48 days
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.
Measured: 16 weeks
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
Measured: Baseline to 17 weeks
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.
Measured: Baseline to 17 weeks
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.
Measured: Baseline to 17 weeks
Effects on Serum Insulin
Mean change in fasting serum insulin between week 17 and baseline.
Measured: Baseline to 17 weeks
Effects on Blood Hemoglobin (Hgb)
Mean change in blood hemoglobin (Hgb) A1C between week 17 and baseline.
Measured: Baseline to 17 weeks
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.
Measured: Baseline to 17 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2014 (estimated)
- Study start13 May 2015
- Primary completion21 Feb 2018
- Study completion17 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-metastatic, Hormone naïve Prostate CancerStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Harrison, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02256111
- Sponsor's protocol ID
- Pro00053924
- Status last verified
- Mar 2019
- First submitted
- 22 Aug 2014
- Last updated
- 18 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 35273377
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02256111
- Acronym / sponsor ID
- Pro00053924
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- 13 May 2015 (actual)
- Primary completion
- 21 Feb 2018 (actual)
- Study completion
- 17 Jul 2018 (actual)
- First posted
- 3 Oct 2014 (estimated)
- Results
- Posted 18 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ENZ+ADT+Usual care | Experimental | Drug: Enzalutamide, Drug: Androgen deprivation therapyThe usual care arm will receive treatment with enzalutamide with androgen deprivation therapy, with no supervised exercise training. |
| ENZ+ADT+Exercise | Experimental | Drug: Enzalutamide, Drug: Androgen deprivation therapy, Behavioral: Supervised exercise trainingThe ENZ+ADT+Exercise arm will receive treatment with enzalutamide plus androgen deprivation therapy along with supervised exercise training. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (49 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnzalutamideAlso: Xtandi | Drug | ENZ+ADT+Exercise, ENZ+ADT+Usual care |
| Androgen deprivation therapy | Drug | ENZ+ADT+Exercise, ENZ+ADT+Usual care |
| Supervised exercise training | Behavioural | ENZ+ADT+Exercise |
Primary outcome
Change in VO2peak in Usual Care Versus Exercise Training Arms
Time frame: From week 1 to week 17
Mean change in peak oxygen uptake (VO2peak) from week 1 to week 17 in the usual care and exercise training groups
14 secondary outcomes
17-week Change in Functional Capacity as Measured by Chair-stand Test
Time frame: Baseline to 17 weeks
17-week Change in Upper and Lower Extremity Maximal Muscular Strength
Time frame: Baseline to 17 weeks
Effects on Serum Glucose
Time frame: Baseline to 17 weeks
Change in the Effect on Patient Reported Outcomes (PROs) of Interest Over Time
Time frame: Baseline to 17 weeks
Eligibility Rate
Time frame: 29 months from study initiation
Acceptance Rate
Time frame: 29 months from study initiation
Adherence Rate
Time frame: 48 days
Attrition Rate
Time frame: 16 weeks
17-week Change in Functional Capacity as Measured by Time Up and Go Test
Time frame: Baseline to 17 weeks
17-week Change in Functional Capacity as Measured by Six Minute Walk Test
Time frame: Baseline to 17 weeks
17-week Change in Muscle Cross-sectional Area (CSA)
Time frame: Baseline to 17 weeks
Effects on Serum Insulin
Time frame: Baseline to 17 weeks
Effects on Blood Hemoglobin (Hgb)
Time frame: Baseline to 17 weeks
Effects on Body Composition
Time frame: Baseline to 17 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35273377Harrison 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Harrison, MD principal investigator
Duke University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Enzalutamide, Androgen deprivation therapy and Supervised exercise training in people with Non-metastatic, Hormone naïve Prostate Cancer, run by Duke University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 49 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in VO2peak in Usual Care Versus Exercise Training Arms (time frame: From week 1 to week 17). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02256111, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2019.