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Everolimus in Treating Patients With Newly Diagnosed Localized Prostate Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by Case Comprehensive Cancer Center.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00526591
First received: September 5, 2007
Last updated: June 14, 2012
Last verified: June 2012

September 5, 2007
June 14, 2012
September 2007
July 2011   (final data collection date for 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 ] [ Designated as safety issue: No ]
    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.
  • Margin status [ Time Frame: After 8 weeks of therapy at the time of prostatectomy ] [ Designated as safety issue: No ]
    Margin status will be assessed by light microscopic examination of histological sections.
  • Capsular penetration [ Time Frame: After 8 weeks of therapy at the time of prostatectomy ] [ Designated as safety issue: No ]
  • Toxicity profile of each dose [ Time Frame: at daily dose for 8 weeks ] [ Designated as safety issue: Yes ]
    Toxicity will be assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAEv3.0, (http://ctep.cancer.gov/forms/CTCAEv3.pdf)).
  • Proportion of patients who are P0 (i.e. no clinically detectable tumor in the pathologic specimen) at surgery
  • Margin status
  • Capsular penetration
  • Toxicity profile of each dose
Complete list of historical versions of study NCT00526591 on ClinicalTrials.gov Archive Site
  • PSA doubling time [ Time Frame: at 4 weeks and 8 weeks during treatment and post-op ] [ Designated as safety issue: No ]
    Time-to-event data, such as PSA doubling time will be summarized using the method of Kaplan and Meier.
  • Effect of treatment on biological and molecular markers [ Time Frame: After 8 weeks of therapy ] [ Designated as safety issue: No ]
    Immunohistochemical Staining of Cellular and Molecular Markers in Prostate Tumor Tissue
  • PSA doubling time
  • Effect of treatment on biological and molecular markers
Not Provided
Not Provided
 
Everolimus in Treating Patients With Newly Diagnosed Localized Prostate Cancer
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • Drug: everolimus
    Low-dose Cohort: Patients will receive 5.0mg P.O. daily continuously for 8 weeks; High-dose Cohort: Patients will receive 10mg P.O. daily continuously for 8 weeks
    Other Name: RAD-001
  • Procedure: conventional surgery
    Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).
  • Experimental: Low-dose Cohort
    Patients will receive 5.0mg P.O. daily continuously for 8 weeks
    Interventions:
    • Drug: everolimus
    • Procedure: conventional surgery
  • Active Comparator: High-dose Cohort
    Patients will receive 10mg P.O. daily continuously for 8 weeks
    Interventions:
    • Drug: everolimus
    • Procedure: conventional surgery
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
17
Not Provided
July 2011   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed newly diagnosed, localized adenocarcinoma of the prostate, meeting any of the following criteria:

    • Clinical stage T2a, T2b, T2c, or T3 disease (any grade or PSA)
    • Gleason score 7 (4+3 only) or ≥ 8 (any stage or PSA)
    • Serum PSA ≥ 10 ng/dL (any grade or stage)
    • Any stage, PSA, or Gleason score AND ≥ 35% chance of biochemical failure at 5 years based on Kattan's nomogram
  • Recommended for radical prostatectomy
  • Normal testosterone level
  • No pure neuroendocrine or small cell prostate cancer
  • No metastatic disease by CT scan, MRI, bone scan, or X-ray
  • No clinical evidence of CNS metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • 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
  • 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

Exclusion criteria:

  • 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
    • 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
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00526591
CASE21806, P30CA043703, CASE-21806, CASE-21806-CC256
Yes
Case Comprehensive Cancer Center
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Jorge A. Garcia, MD Case Comprehensive Cancer Center
Case Comprehensive Cancer Center
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP