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Prostate AdenocarcinomaPhase 2NCT02268175

Enzalutamide/Leuprolide +/- Abiraterone/Pred in Prostate

A Phase 2 study testing Enzalutamide, Abiraterone Acetate and Prednisone in people with Prostate Adenocarcinoma and Prostate Cancer, run by Dana-Farber Cancer Institute at 4 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

This study is comparing the effectiveness of enzalutamide with or without abiraterone acetate for men with high-risk, localized prostate cancer. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Enzalutamide, Abiraterone Acetate and Prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
4 sitesUnited States
Study dates
Oct 2014to Dec 2021
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 greater than or equal 18 years of age.
  • Histologically confirmed adenocarcinoma of the prostate without histological variants (including overt neuroendocrine differentiation, small cell neuroendocrine carcinoma features, sarcomatoid features, pure ductal adenocarcinoma, squamous or transitional cell carcinoma).
  • Must have tissue available from the pre-treatment diagnostic biopsy (tissue blocks if possible; if not possible, 10 unstained slides from each positive core sample for a total of 30 slides).
  • Must have three core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained). Prostate biopsy must be within three months from screening.
  • Participants must have the following features:
  • Intermediate-risk disease defined as Gleason 4+3=7 disease OR
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  • High-risk disease defined as Gleason 8-10 OR PSA > 20 ng/dL OR T3 disease (by prostate MRI)
  • No evidence of metastatic or nodal disease as determined by radionuclide bone scans CT/MRI.
  • Participants must be candidates for RP and considered surgically resectable by urologic evaluation.
  • ECOG performance status 0 to 1 (Appendix A).
  • Participants must have normal organ and marrow function as defined below:
  • WBC ≥ 3,000/mcL
  • ANC ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Serum potassium ≥ 3.5 mmol/L
  • AST, ALT, and total bilirubin ≤ 1.5 x Institutional ULN
  • Calculated creatinine clearance ≥ 60 mL/min
  • PTT ≤ 60, INR ≤ 1.5 x Institutional ULN unless on warfarin therapy (investigator would need to determine if safe for participant to stop warfarin prior to biopsy and warfarin therapy)
  • Controlled blood pressure defined as a systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg on no more than three anti-hypertensive agents. Drug formulations containing two or more anti-hypertensive agents will be counted based on the number of active agents in each formulation.

Who cannot join

  • Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, ARN-509 and others), CYP17 inhibitors (including abiraterone, TAK-700, galeterone, ketoconazole, and others), estrogens, LHRH agonist/antagonists. Prior therapy with 5α-reductace inhibitors is allowed. LHRH therapy allowed if begun within 4 weeks of day 1.
  • Prior chemotherapy, radiation therapy, or immunotherapy for prostate cancer.
  • Prior systemic treatment with an azole drug within four weeks of screening visit.
  • Hypogonadism or severe androgen deficiency as defined by screening serum testosterone < 200 ng/dL.
  • Clinically significant cardiovascular disease including:
  • Acute coronary syndrome within 6 months of screening visit;
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  • Hypotension defined as a systolic blood pressure < 86 mmHg;
  • Bradycardia defined as a heart rate of < 50 beats per minute, unless pharmaceutically induced and thus reversible (i.e. beta blockers);
  • Uncontrolled angina (requiring escalating doses of nitrates) within 3 months of screening visit;
  • Congestive heart failure NYHA Class III or IV or subjects with a history of congestive heart failure NYHA Class III or IV, unless screening ECHO results in left ventricular ejection fraction that ≥ 45%;
  • History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes);
  • Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on screening EKG > 470 msec;
  • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
  • History of seizure or any condition or concurrent medication that may predispose to seizure.
  • Thromboembolism within 6 months of screening visit.
  • Severe hepatic impairment (Child-Pugh Class C).
  • Active or symptomatic viral hepatitis or chronic liver disease.
  • History of pituitary or adrenal dysfunction.
  • GI disorders which may interfere with the absorption of the study drug.
  • Pre-existing condition that warrants long-term corticosteroid use.
  • Concomitant use of medications that may alter pharmacokinetics of abiraterone or enzalutamide.
  • Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1) individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, or 2) individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: non-muscle invasive bladder cancer, basal cell or squamous cell carcinoma of the skin.
  • Major surgery or radiation therapy within 30 days of screening.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21231

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • University of Washington

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase II Randomized Study of Enzalutamide+Leuprolide Versus Enzalutamide+Leuprolide+Abiraterone Acetate+Prednisone as Neoadjuvant Therapy for HIgh-Risk Prostate Cancer Undergoing Prostatectomy

This study is comparing the effectiveness of enzalutamide with or without abiraterone acetate for men with high-risk, localized prostate cancer.

Read the detailed description

In this research study, the investigators are comparing the effectiveness of enzalutamide with or without abiraterone acetate for men with high-risk, localized prostate cancer.

Abiraterone acetate with prednisone and enzalutamide are currently FDA-approved for use in the treatment of patients with metastatic castration-resistant prostate cancer, however they are investigational for the treatment of localized prostate cancer. Abiraterone acetate works by decreasing the production of male sex hormones, which cause prostate cancer growth. Enzalutamide works by blocking the effects of male sex hormones, which cause prostate cancer growth.

The FDA (the U.S. Food and Drug Administration) has not approved the combination of enzalutamide and abiraterone acetate as neoadjuvant therapy for high risk prostate cancer undergoing prostatectomy but each drug has been approved for the treatment of more advanced prostate cancer.

Participants will be randomized to one of two study arms. Randomization means that the participant is put into a group by chance. It is like flipping a coin. Neither participant nor the research doctor will choose what group participants are randomized to.

The names of the study medications involved in this study are:

  • Enzalutamide
  • Abiraterone Acetate
  • Prednisone
  • Leuprolide Acetate
Being tested
Enzalutamide, Abiraterone Acetate, Prednisone, Leuprolide Acetate
Keywords
prostate adenocarcinoma, advanced prostate cancer, high risk prostate cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • EnzalutamideDrug

    Also called XTANDI

    160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Can be taken with or without food.

  • Abiraterone AcetateDrug

    Also called Zytiga

    1000 mg (four 250 mg tablets), oral, once daily, 28 days (4 weeks) 6 cycles maximum. No food should be consumed for at least two hours before the dose and for at least one hour after the dose.

  • PrednisoneDrug

    5 mg, oral, once daily, 28 days (4 weeks) 6 cycles maximum.Take with food, preferred to be taken in the morning .

  • Leuprolide AcetateDrug

    Also called - Lupron Depot-3 Month, - Lupron Depot-4 Month, - Lupron Depot, - Lupron

    Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.

Study groups in NCT02268175
Study groupRoleWhat they receive
ARM 1ExperimentalParticipants will be randomized in a 2:1 ratio to neoadjuvant treatment (ARM 1) or (ARM 2). Participants will receive the assigned study treatment per cycle * Enzalutamide- Once daily at prespecified dose, orally * Abiraterone Acetate- Once daily at prespecified dose, orally * Prednisone-Once daily at prespecified dose, orally * Leuprolide Acetate-Intermuscular injection at prespecified dose and duration
Receives: Drug: Enzalutamide; Drug: Abiraterone Acetate; Drug: Prednisone; Drug: Leuprolide Acetate
ARM 2ExperimentalParticipants will be randomized in a 2:1 ratio to neoadjuvant treatment (ARM 1) or (ARM 2). Participants will receive the assigned study treatment per cycle. * Enzalutamide- once daily at prespecified dose, orally * Leuprolide Acetate- Intermuscular injection at prespecified dose and duration
Receives: Drug: Enzalutamide; Drug: Leuprolide Acetate

What is being measured

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

  1. Percentage of Participants With Pathologic Complete Response (pCR) or Minimal Residual Disease (MRD)

    pCR is defined as the absence of morphologically identifiable carcinoma in the radical prostatectomy (RP) specimen. MRD is defined as the largest cross-sectional dimension of residual tumor measuring </= 0.5 cm. If the tumor is multifocal, the size of the largest focus will be used to determine the size of the residual tumor.

    Measured: after RP approximately 24 weeks from study entry

Secondary outcomes (4)

  1. Participants With Pathologic Complete Response (pCR)

    pCR is defined as the absence of morphologically identifiable carcinoma in the radical prostatectomy (RP) specimen.

    Measured: after RP approximately 24 weeks from study entry

  2. Residual Cancer Burden (RCB)

    RCB was analyzed using radical prostatectomy (RP) tissue. The largest area of tumor was measured by ruler and the longest tumor dimension in this area was used as the dimension for calculation.

    Measured: after RP approximately 24 weeks from study entry

  3. Positive Surgical Margin Status

    Participants were classified by presence or absence of positive surgical margins defined as margins, which are the edges of the removed tumor, that show some cancer cells.

    Measured: after RP approximately 24 weeks from study entry

  4. Median Prostate Specific Antigen (PSA) Nadir

    PSA nadir is the lowest PSA level recorded during neoadjuvant therapy.

    Measured: PSA was assessed at baseline and every cycle during neoadjuvant therapy (up to 24 weeks).

Timeline

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

  1. First posted20 Oct 2014 (estimated)
  2. Study startOct 2014
  3. Primary completionJan 2018
  4. Study completionDec 2021

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
Single group
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02268175
Sponsor's protocol ID
14-283
Status last verified
Mar 2022
First submitted
14 Oct 2014
Last updated
19 Apr 2022
Data monitoring committee
Yes

Publications

  • Lin HM, Yang X, Centenera MM, Huynh K, Giles C, Dehairs J, Swinnen JV, Hoy AJ, Meikle PJ, Butler LM, Taplin ME, Horvath LG. Circulating Lipid Profiles Associated With Resistance to Androgen Deprivation Therapy in Localized Prostate Cancer. JCO Precis Oncol. 2024 Jul;8:e2400260. doi: 10.1200/PO.24.00260.

    PubMed 39074346

  • McKay RR, Ye H, Xie W, Lis R, Calagua C, Zhang Z, Trinh QD, Chang SL, Harshman LC, Ross AE, Pienta KJ, Lin DW, Ellis WJ, Montgomery B, Chang P, Wagner AA, Bubley GJ, Kibel AS, Taplin ME. Evaluation of Intense Androgen Deprivation Before Prostatectomy: A Randomized Phase II Trial of Enzalutamide and Leuprolide With or Without Abiraterone. J Clin Oncol. 2019 Apr 10;37(11):923-931. doi: 10.1200/JCO.18.01777. Epub 2019 Feb 27.

    PubMed 30811282

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Enzalutamide, Abiraterone Acetate and Prednisone in people with Prostate Adenocarcinoma and Prostate Cancer, run by Dana-Farber Cancer Institute at 4 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 19 inclusion and 23 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 19 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 8 Oct 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?

Percentage of Participants With Pathologic Complete Response (pCR) or Minimal Residual Disease (MRD) (time frame: after RP approximately 24 weeks from study entry). 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 NCT02268175, which also lists 2 linked publications.

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 19 Apr 2022.

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