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Everolimus in Treating Patients With Newly Diagnosed Localized Prostate Cancer
This study has been terminated.
First Received: September 5, 2007   Last Updated: March 25, 2008   History of Changes
Sponsors and Collaborators: Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00526591
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: everolimus
Procedure: conventional surgery
Procedure: diagnostic procedure
Procedure: enzyme inhibitor therapy
Procedure: immunohistochemistry staining method
Procedure: laboratory biomarker analysis
Procedure: neoadjuvant therapy
Phase II

MedlinePlus related topics: Cancer Prostate Cancer Surgery
Drug Information available for: Everolimus
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized
Official Title: Randomized Phase II Study of Two Different Doses of RAD-001 (Everolimus) as Neo-Adjuvant Therapy in Patients With Localized Prostate Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of patients who are P0 (i.e., no clinically detectable tumor in the pathologic specimen) at surgery [ Designated as safety issue: No ]
  • Margin status [ Designated as safety issue: No ]
  • Capsular penetration [ Designated as safety issue: No ]
  • Toxicity profile of each dose [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • PSA doubling time [ Designated as safety issue: No ]
  • Effect of treatment on biological and molecular markers [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: September 2007
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00526591

Locations
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Study Chair: Jorge A. Garcia, MD Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000564323, CASE-21806, CASE-21806-CC256, NOVARTIS-CASE-21806
Study First Received: September 5, 2007
Last Updated: March 25, 2008
ClinicalTrials.gov Identifier: NCT00526591     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the prostate
stage I prostate cancer
stage II prostate cancer
stage III prostate cancer

Study placed in the following topic categories:
Everolimus
Oxymetazoline
Immunologic Factors
Prostatic Diseases
Genital Neoplasms, Male
Phenylephrine
Adjuvants, Immunologic
Urogenital Neoplasms
Genital Diseases, Male
Adenocarcinoma
Immunosuppressive Agents
Prostatic Neoplasms

Additional relevant MeSH terms:
Everolimus
Genital Neoplasms, Male
Prostatic Diseases
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Urogenital Neoplasms
Enzyme Inhibitors
Genital Diseases, Male
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Prostatic Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009