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Trial record 23 of 278 for:    prostate cancer AND localized | ( Map: United States )

Everolimus in Treating Patients With Newly Diagnosed Localized Prostate Cancer

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ClinicalTrials.gov Identifier: NCT00526591
Recruitment Status : Terminated (Slow accrual)
First Posted : September 10, 2007
Results First Posted : December 6, 2018
Last Update Posted : December 6, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jorge A. Garcia, MD, Case Comprehensive Cancer Center

Brief 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.

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 or disease Intervention/treatment Phase
Prostate Cancer Drug: Everolimus Procedure: conventional surgery Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of Two Different Doses of RAD-001 (Everolimus) as Neo-Adjuvant Therapy in Patients With Localized Prostate Cancer
Study Start Date : September 2007
Actual Primary Completion Date : July 2011
Actual Study Completion Date : August 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Low-dose Everolimus Cohort
5mg Everolimus daily continuously for 8 weeks and conventional surgery
Drug: Everolimus
Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week
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).

Active Comparator: High-dose Everolimus Cohort
10mg Everolimus daily continuously for 8 weeks and conventional surgery
Drug: Everolimus
Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week
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).




Primary Outcome Measures :
  1. 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 ]
    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.

  2. Toxicity Profile of Each Dose (Number of Patients With Worst Grade Toxicity) [ Time Frame: at daily dose for 8 weeks ]
    Toxicity will be assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAEv3.0)


Secondary Outcome Measures :
  1. Change in PSA [ Time Frame: Up to 16 weeks after start of study ]
    Time-to-event data, such as change in PSA will be summarized using the method of Kaplan and Meier.


Other Outcome Measures:
  1. Effect of Treatment on Biological and Molecular Markers [ Time Frame: After 8 weeks of therapy ]
    Immunohistochemical Staining of Cellular and Molecular Markers in Prostate Tumor Tissue



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00526591


Locations
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United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Jorge A. Garcia, MD
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jorge A. Garcia, MD Case Comprehensive Cancer Center

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Jorge A. Garcia, MD, Principal Investigator, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00526591     History of Changes
Other Study ID Numbers: CASE21806
P30CA043703 ( U.S. NIH Grant/Contract )
CASE-21806 ( Other Identifier: Case Comprehensive Cancer Center )
CASE-21806-CC256 ( Other Identifier: Cancer Center IRB )
First Posted: September 10, 2007    Key Record Dates
Results First Posted: December 6, 2018
Last Update Posted: December 6, 2018
Last Verified: November 2018
Keywords provided by Jorge A. Garcia, MD, Case Comprehensive Cancer Center:
adenocarcinoma of the prostate
stage I prostate cancer
stage II prostate cancer
stage III prostate cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Genital Diseases, Male
Sirolimus
Everolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents