AzTrials
AzTrials

Castration Resistant Metastatic Prostate CancerPhase 2TransformerNCT02286921

Testosterone Revival Abolishes Negative Symptoms, Fosters Objective Response and Modulates Enzalutamide Resistance

A Phase 2 study testing Testosterone cypionate, Enzalutamide and Testosterone Enanthate in people with Castration Resistant Metastatic Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Asymptomatic men with progressive metastatic Castration-resistant prostate cancer (CRPC) post- treatment with abiraterone acetate (pre-chemotherapy for metastatic disease) will be treated on a randomized, multi-Institutional open label study to determine if treatment with intramuscular T given on a dose/schedule… Read more about this study

Who is it for?
Ages 18 to 80 years, men only
What is being tested?
Testosterone cypionate, Enzalutamide and Testosterone Enanthate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
222 participants
Where
17 sitesUnited States
Study dates
Jan 2015to 21 Feb 2020
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 to 80 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Eastern Cooperative Oncology Group Performance status ≤2
  • Age ≥18 years
  • Histologically-confirmed adenocarcinoma of the prostate
  • Treated with continuous androgen ablative therapy (either surgical castration or luteinizing hormone-releasing hormone agonist/antagonist)
  • Documented castrate level of serum testosterone (<50 ng/dl)
  • Metastatic disease radiographically documented by CT/MRI or bone scan.
Show all 29Show fewer
  • Must have had disease progression while on abiraterone acetate alone or abiraterone acetate in combination with other investigational agents based on:
  • Prostate-specific antigen progression defined as an increase in Prostate-specific antigen, as determined by 2 separate measurements taken at least 1 week apart
  • And/Or
  • Radiographic disease progression, based on RECIST 1.1 in patients with measurable soft tissue lesions, or PCWG2 for patients with bone disease
  • Screening Prostate-specific antigen must be ≥ 1.0 ng/mL.
  • Prior treatment with additional second line hormone therapies is allowed.
  • No prior treatment with enzalutamide, Apalutamide (ARN-509), Darolutamide (ODM-201), galeterone or other investigational androgen receptor targeted treatment is allowed.
  • Prior docetaxel for hormone-sensitive prostate cancer is permitted if ≤ 6 doses were given in conjunction with first-line androgen deprivation therapy and >12 months since last dose of docetaxel.
  • Prior treatment with Provenge vaccine and 223Radium (Xofigo) is allowed if >4 weeks from last dose.
  • Patients must be withdrawn from abiraterone for ≥ 2 weeks.
  • Patients must be weaned off prednisone and be off therapy for ≥ 1 week prior to starting therapy.
  • Acceptable liver function:
  • Bilirubin < 2.5 times institutional upper limit of normal (ULN)
  • aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) < 2.5 times ULN
  • Acceptable renal function:
  • Serum creatinine < 2.5 times ULN
  • Acceptable hematologic status:
  • Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
  • Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
  • Hemoglobin ≥ 9 g/dL.
  • At least 4 wks since prior radiation.
  • Ability to understand and willingness to sign a written informed consent document.
  • Patients on either treatment arm will be considered for crossover if they demonstrate evidence of radiographic disease progression.

Who cannot join

  • Pain due to metastatic prostate cancer requiring treatment intervention.
  • Eastern Cooperative Oncology Group Performance status ≥3
  • Prior treatment with enzalutamide is prohibited
  • Prior treatment with docetaxel or cabazitaxel for metastatic castration-resistant prostate cancer is prohibited.
  • Requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement well documented to be due to prostate cancer or benign prostatic hyperplasia (BPH).
  • Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g. femoral metastases with concern over fracture risk, severe and extensive spinal metastases with concern over spinal cord compression, extensive liver metastases)
Show all 13Show fewer
  • Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
  • Active uncontrolled infection, including known history of HIV/AIDS or hepatitis B or C.
  • Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
  • Patients receiving anticoagulation therapy with Coumadin are not eligible for study. [Patients on non-coumadin anticoagulants (Lovenox, Xarelto, etc.) are eligible for study. Patients on Coumadin who can be transitioned to lovenox prior to starting study treatments will be eligible].
  • Patients with prior history of a thromboembolic event within the last 12 months that is not being treated with systemic anticoagulation are excluded.
  • Patients allergic to sesame seed oil or cottonseed oil are excluded.
  • Major surgery (eg, requiring general anesthesia) within 3 weeks before screening, or has not fully recovered from prior surgery (ie, unhealed wound). Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate.

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Piedmont Cancer Institute

    Atlanta, Georgia, 30318

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • University of Maryland

    Baltimore, Maryland, 21201

  • SKCCC at Johns Hopkins

    Baltimore, Maryland, 21205

  • Unversity of Alabama

    Birmingham, Alabama, 35294

  • University of Chicago

    Chicago, Illinois, 60637

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • City of Hope

    Duarte, California, 91010

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08901

  • Tulane University Medical Center

    New Orleans, Louisiana, 70112

  • Neraska Cancer Specialists

    Omaha, Nebraska, 68130

  • Allegheny Health Network

    Pittsburgh, Pennsylvania, 15212

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • University of Washing

    Seattle, Washington, 98109

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

Other trials in United States

About this study

Official title: A Randomized Phase II Study Comparing Bipolar Androgen Therapy vs. Enzalutamide in Asymptomatic Men With Castration Resistant Metastatic Prostate Cancer

Asymptomatic men with progressive metastatic Castration-resistant prostate cancer (CRPC) post- treatment with abiraterone acetate (pre-chemotherapy for metastatic disease) will be treated on a randomized, multi-Institutional open label study to determine if treatment with intramuscular T given on a dose/schedule designed to result in rapid cycling from the polar extremes of supraphysiologic to near castrate levels [i.e. Bipolar Androgen Therapy (BAT)] will improve primary and secondary objectives vs. enzalutamide as standard therapy.

Read the detailed description

Eligible patients will have metastatic CRPC with no disease related symptoms and progression on Androgen deprivation therapy and will have progressed post-treatment with abiraterone. Patients will continue on Androgen deprivation therapy with Luteinising Hormone Releasing Hormone agonist (i.e. Zoladex, Trelstar, Eligard or Lupron) or Luteinising Hormone Releasing Hormone antagonist (Degarelix) if not surgically castrated throughout the duration of the study to inhibit endogenous testosterone production. Patients will be randomized 1:1 and stratified based on duration of prior abiraterone acetate therapy (6 months or less or greater than 6 months). Patients randomized to BAT (Arm A) will receive intramuscular injections with either testosterone cypionate or testosterone enanthate at a dose of 400 mg every 28 days. This dose was selected based on data demonstrating that it produces an initial supraphysiologic serum level of T (i.e. > 1500 ng/dL or 3-10 times normal level) with eugonadal levels achieved at the end of two weeks and near castrate levels after 28 days. Patients randomized to enzalutamide (Arm B) will receive daily oral dose of 160 mg. Each cycle is defined as 28 days.

Patients will have Prostate-specific antigen level and symptoms assessment checked every cycle. Every 3 cycles patients will have repeat bone/CT scans to evaluate treatment response status. On CT scan, radiographic progression will be defined by RECIST criteria (i.e. >20% increase in the sum of target lesions). On bone scan, radiographic progression will be defined by PCWG2 criteria as ≥ 2 new bone lesions. However, for the first reassessment scan only, patients should remain on study and have a confirmatory scan performed 12 weeks (3 cycles) later. If this confirmatory scan shows 2 or more additional new lesions, this defines progression. The date of progression is the date of the first reassessment bone scan. If the confirmatory scan does not show any additional new lesions, patient remains on study. If progression is observed on subsequent bone scans, a confirmatory scan is not required; the date of this bone scan is the date of progression.

Patients with Prostate-specific antigen progression but with disease response or stable disease on imaging studies will remain on study until radiographic or other clinical progression criteria are met. Patients with radiographic disease progression will not receive continued BAT (arm A) or enzalutamide (arm B) and will be eligible for crossover to the opposite therapy. Patients on the BAT arm A can cross over to receive enzalutamide at time of progression or can choose to go off study and be treated with other standard of care treatments. Patients on the enzalutamide arm B will be allowed to cross-over to receive BAT or can choose to go off study and be treated with other standard of care treatments.

Patients with clinical progression due to prostate cancer must meet study exclusion criteria to be permitted to cross-over to the opposite treatment. Patients with clinical progression due to pain from prostate cancer are not permitted to cross-over.

Being tested
Testosterone cypionate, Enzalutamide, Testosterone Enanthate
Keywords
Testosterone, Enzalutamide, Abiraterone, Androgen Ablative Therapies, Bipolar Androgen Therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Testosterone cypionateDrug

    Also called Depo-Testosterone Injection

    Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate.

  • EnzalutamideDrug

    Also called Xtandi

    Enzalutamide is a white crystalline non-hygroscopic solid. It is practically insoluble in water. Enzalutamide is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. The inactive ingredients are caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, and black iron oxide.

  • Testosterone EnanthateDrug

    Also called Delatestryl

    Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.

Study groups in NCT02286921
Study groupRoleWhat they receive
Arm A: Testosterone cypionate or testosterone enanthateExperimentalPatients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days.
Receives: Drug: Testosterone cypionate; Drug: Testosterone Enanthate
Arm B: EnzalutamideExperimentalPatients randomized to enzalutamide will be prescribed enzalutamide 40 mg tablets and instructed to take 4 tablets per day orally for 28 days/cycle.
Receives: Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival as Measured by Number of Months Until Clinical or Radiographic Progression

    Time to clinical progression will be defined as months from randomization to any of the following (whichever occurs earlier):

    • Cancer pain requiring initiation of chronic administration of opiate analgesia (oral opiate use for ≥3 weeks; parenteral opiate use for ≥7 days. Patients with cancer pain requiring opiate analgesia for relief should also be assessed by the investigator for the need for initiating systemic chemotherapy or palliative radiation.
    • Development of a skeletal-related event (SRE): pathologic fracture, spinal cord compression, or need for surgical intervention or radiation therapy to the bone.
    • Development of clinically significant symptoms due to loco-regional tumor progression (e.g. urinary obstruction) requiring surgical intervention or radiation therapy.

    Measured: up to 2 years

Secondary outcomes (13)

  1. Radiographic Progression

    Number of months until 20% increase in the sum of target lesions on CT scans.

    Measured: up to 2 years

  2. Prostate-Specific Antigen Response Rate

    Number of participants achieving a Prostate-Specific Antigen decline ≥ 50% according to Prostate Cancer Working Group (PCWG2) criteria.

    Measured: Up to 2 years

  3. Objective Response Rate as Determined by RECIST

    Number of participants with partial (PR) or complete response (CR) as defined by response evaluation criteria in solid tumors (RECIST), where CR is a disappearance of all target lesions and PR is ≥30% reduction in the sum of the longest diameter of target lesions.

    Measured: Up to 2 years

  4. Time to Prostate-Specific Antigen Progression

    Reported as number of months till Prostate-Specific Antigen increase of greater or equal to 50% according to Prostate Cancer Working Group (PCWG2) criteria.

    Measured: Up to 2 years

  5. Quality of Life as Assessed by the Positive Affect Score of the Positive and Negative Affect Schedule (PANAS)

    The Positive Affect Score is calculated by adding the scores on items 1, 3, 5, 9, 10, 12, 14, 16, 17, and 19. Scores can range from 10 - 50, with higher scores representing higher levels of positive affect.

    Measured: up to 1 year

  6. Quality of Life as Assessed by the Negative Affect Score of the Positive and Negative Affect Schedule (PANAS)

    The Negative Affect Score is calculated by adding the scores on items 2, 4, 6, 7, 8, 11, 13, 15, 18, and 20. Scores can range from 10 - 50, with lower scores representing lower levels of negative affect.

    Measured: up to 1 year

  7. Change in Quality of Life as Assessed by the International Index of Erectile Function (IIEF) Questionnaire

    The IIEF assesses erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), orgasmic satisfaction (OS). Each of domains are scored on a scale of 0 to 5 with a lower score indicating a bad quality sex life. The IIEF questionnaire has a total score that ranges from 5 to 25 with lower score indicating less erectile dysfunction. A positive change in the score reflects better outcome.

    Measured: up to 1 year

  8. Quality of Life as Assessed by Short Form 36

    All questions are scored on a scale from 0 to 100. The total score from all of the questions answered is divided by the total number of the questions answered yielding a global score from 0-100 with 100 representing the highest level of functioning possible.

    Measured: up to 1 year

  9. Quality of Life as Assessed by FACIT Fatigue Scale

    The Functional Assessment of Chronic Illness Therapy - Fatigue has a score range of 0-52 with higher scores indicating better quality of life.

    Measured: up to 1 year

  10. Pain Severity as Assessed by the Brief Pain Inventory

    Severity is calculated by adding the scores for questions 2, 3, 4 and 5 and then dividing by 4. This gives a severity score out of 10, high score indicates more severe pain.

    Measured: 1 year

  11. Pain Interference as Assessed by the Brief Pain Inventory

    Interference is calculated by adding the scores for questions 8a, b, c, d, e, f and g and then dividing by 7. This gives an interference score out of 10, higher score indicates more pain interference.

    Measured: 1 year

  12. Overall Survival

    Time until death for any reasons

    Measured: up to 3 years

  13. Progression Free Survival on Crossover Treatment

    Time from initiation of therapy to progression on crossover treatment

    Measured: up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Nov 2014 (estimated)
  2. Study startJan 2015
  3. Primary completion26 Oct 2018
  4. Study completion21 Feb 2020

Resources

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
222 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02286921
Sponsor's protocol ID
J14146
Other IDs
IRB00046414, W81XWH-14-2-0189
Acronym
Transformer
Status last verified
Jul 2020
First submitted
22 Oct 2014
Last updated
6 Nov 2020
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Denmeade SR, Wang H, Agarwal N, Smith DC, Schweizer MT, Stein MN, Assikis V, Twardowski PW, Flaig TW, Szmulewitz RZ, Holzbeierlein JM, Hauke RJ, Sonpavde G, Garcia JA, Hussain A, Sartor O, Mao S, Cao H, Fu W, Wang T, Abdallah R, Lim SJ, Bolejack V, Paller CJ, Carducci MA, Markowski MC, Eisenberger MA, Antonarakis ES. TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Metastatic Prostate Cancer. J Clin Oncol. 2021 Apr 20;39(12):1371-1382. doi: 10.1200/JCO.20.02759. Epub 2021 Feb 22.

    PubMed 33617303

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Testosterone cypionate, Enzalutamide and Testosterone Enanthate in people with Castration Resistant Metastatic Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 17 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 29 inclusion and 13 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 6 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 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 1 May 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?

Progression Free Survival as Measured by Number of Months Until Clinical or Radiographic Progression (time frame: up to 2 years). 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 NCT02286921, 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 6 Nov 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in