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Prostate CancerPhase 2NCT00526591

Everolimus in Treating Patients With Newly Diagnosed Localized Prostate Cancer

A Phase 2 study testing Everolimus and conventional surgery in people with Prostate Cancer, run by Jorge A. Garcia, MD at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving everolimus before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Read more about this study

Who is it for?
Ages 18 to 120 years, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Everolimus and conventional surgery
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
Sep 2007to Aug 2011
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 120 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%
  • ANC ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Hemoglobin ≥ 8 g/dL
  • AST and ALT ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
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  • Creatinine ≤ 1.5 times ULN
  • PT/PTT normal (no anticoagulants)
  • No active unresolved infection
  • No known HIV positivity
  • Fertile patients must use effective contraception during and for 6 months after completion of study therapy

Who cannot join

  • Known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus or temsirolimus) or to its excipients
  • Gastrointestinal (GI) disease, condition, or symptoms that may significantly impair GI function and alter the absorption of everolimus, including any of the following:
  • Ulcerative disease
  • Uncontrolled nausea
  • Vomiting
  • Diarrhea
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  • Malabsorption syndrome
  • Other active malignancy or malignancy at ≥ 30% risk for relapse after completion of therapy, except nonmelanoma skin cancer
  • Uncontrolled concurrent illness including, but not limited to, any of the following:
  • Ongoing or active infection (e.g., bacterial, viral or fungal)
  • Severely impaired lung function
  • Uncontrolled diabetes (fasting serum glucose > 1.5 times ULN)
  • Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent hepatitis)
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would limit study compliance
  • Any underlying medical condition which, in the principal investigator's opinion, will make the administration of everolimus hazardous OR obscure the interpretation of adverse events
  • PRIOR CONCURRENT THERAPY:
  • More than 4 weeks since major surgery
  • More than 3 months since finasteride
  • No prior or concurrent radiotherapy to the prostate gland or pelvis
  • No prior hormones (e.g., luteinizing hormone-releasing hormone [LHRH] agonists, LHRH antagonists, or antiandrogens [e.g., bicalutamide, flutamide, or nilutamide]) and/or PC-SPES (or PC-x product) or estrogen-containing nutraceuticals
  • No prior rapamycin mTOR inhibitor
  • No prior small bowel resection that may significantly impair GI function and alter the absorption of everolimus
  • No prior or concurrent immunotherapy, chemotherapy, or other investigational therapy for prostate cancer
  • No other concurrent investigational or commercial agents
  • No other concurrent anticancer agents
  • No concurrent, chronic treatment with systemic steroids (except inhaled or topical steroids) or another immunosuppressive agent
  • No concurrent live vaccines
  • No concurrent strong inhibitors or inducers of the isoenzyme CYP3A administered as systemic therapy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44195

Other trials in United States

About this study

Official title: Randomized Phase II Study of Two Different Doses of RAD-001 (Everolimus) as Neo-Adjuvant Therapy in Patients With Localized Prostate Cancer

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving everolimus before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This randomized phase II trial is studying the side effects and how well everolimus works in treating patients with newly diagnosed localized prostate cancer.

Read the detailed description

OBJECTIVES:

Primary

  • To determine the clinical effects of everolimus, in terms of pathologic response (i.e., histologic P0, margin status, or capsular penetration) and surgical outcome, in patients with newly diagnosed localized prostate cancer treated with two different doses of everolimus prior to radical prostatectomy.
  • To evaluate the safety and tolerability of this drug in these patients.

Secondary

  • To determine the effect of this drug on prostate-specific antigen (PSA) levels in these patients.
  • To determine the effect of this drug on levels of expression of PTEN, Akt, phospho-mTOR (i.e., Se2448), phospho-p70 S6 kinase (i.e., Thre389), phospho-Smad3 (i.e., Ser433/435), phospho-Smads 1/5 (i.e., Ser463/465), AR, and TUNEL in these patients.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive low-dose oral everolimus once daily for up to 8 weeks in the absence of unacceptable toxicity.
  • Arm II: Patients receive high-dose oral everolimus once daily for up to 8 weeks in the absence of unacceptable toxicity.

Within 7 days after the last dose of everolimus, all patients undergo radical prostatectomy with bilateral pelvic lymphadenectomy.

Tumor biopsy specimens acquired prior to treatment and prostate tumor tissue acquired at the time of radical prostatectomy are evaluated for biomarker correlative studies. Tissue samples are assessed by immunohistochemistry (IHC) and tissue microarray analysis for expression of cellular and molecular biomarkers (i.e., p-S6, p-4E-BP1, and p-Akt) that correlate with response. Prostatectomy specimens are also assessed by pathologic analysis for histopathologic response (i.e., pathologic stage, Gleason score, margin status, and tumor size).

After completion of study therapy, patients are followed at 6 weeks.

Conditions
Prostate Cancer
Keywords
adenocarcinoma of the prostate, stage I prostate cancer, stage II prostate cancer, stage III 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.

  • EverolimusDrug

    Also called RAD-001

    Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week

  • conventional surgeryProcedure or surgery

    Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).

Study groups in NCT00526591
Study groupRoleWhat they receive
Low-dose Everolimus CohortExperimental5mg Everolimus daily continuously for 8 weeks and conventional surgery
Receives: Drug: Everolimus; Procedure: conventional surgery
High-dose Everolimus CohortActive comparator10mg Everolimus daily continuously for 8 weeks and conventional surgery
Receives: Drug: Everolimus; Procedure: conventional surgery

What is being measured

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

  1. Proportion of Patients Who Are P0 (i.e., no Clinically Detectable Tumor in the Pathologic Specimen) at Surgery

    Specimens are fixed in formalin for 24 hours.Specimens are the cut at 3 mm intervals perpendicular to the rectal surface and the sections are examined grossly and microscopically on routine Hematoxylin and Eosin stain (H\&E) (pathologic complete response or P0) will be defined as responders.

    Measured: After 8 weeks of therapy at the time of prostatectomy

  2. Toxicity Profile of Each Dose (Number of Patients With Worst Grade Toxicity)

    Toxicity will be assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAEv3.0)

    Measured: at daily dose for 8 weeks

Secondary outcomes (1)

  1. Change in PSA

    Time-to-event data, such as change in PSA will be summarized using the method of Kaplan and Meier.

    Measured: Up to 16 weeks after start of study

Timeline

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

  1. First posted10 Sep 2007 (estimated)
  2. Study startSep 2007
  3. Primary completionJul 2011
  4. Study completionAug 2011

Why it stopped: Slow accrual

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
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00526591
Sponsor's protocol ID
CASE21806
Other IDs
P30CA043703, CASE-21806, CASE-21806-CC256
Status last verified
Nov 2018
First submitted
5 Sep 2007
Last updated
6 Dec 2018
Data monitoring committee
Yes

Publications

  • Koshkin VS, Mir MC, Barata P, Gul A, Gupta R, Stephenson AJ, Kaouk J, Berglund R, Magi-Galluzzi C, Klein EA, Dreicer R, Garcia JA. Randomized phase II trial of neoadjuvant everolimus in patients with high-risk localized prostate cancer. Invest New Drugs. 2019 Jun;37(3):559-566. doi: 10.1007/s10637-019-00778-4. Epub 2019 Apr 30.

    PubMed 31037562

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Everolimus and conventional surgery in people with Prostate Cancer, run by Jorge A. Garcia, MD at 1 site 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 11 inclusion and 31 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: stopped early, as of the sponsor's last update on 6 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 6 Dec 2018). 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?

Proportion of Patients Who Are P0 (i.e., no Clinically Detectable Tumor in the Pathologic Specimen) at Surgery (time frame: After 8 weeks of therapy at the time of prostatectomy). The study lists 2 primary outcomes in all. 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 NCT00526591, 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 Dec 2018.

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