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Everolimus in Treating Patients With Newly Diagnosed Localized Prostate Cancer

14 november 2018 uppdaterad av: Jorge A. Garcia, MD

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.

Studieöversikt

Status

Avslutad

Betingelser

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

17

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

    • Ohio
      • Cleveland, Ohio, Förenta staterna, 44195
        • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 120 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Manlig

Beskrivning

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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Low-dose Everolimus Cohort
5mg Everolimus daily continuously for 8 weeks and conventional surgery
Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week
Andra namn:
  • RAD-001
Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).
Aktiv komparator: High-dose Everolimus Cohort
10mg Everolimus daily continuously for 8 weeks and conventional surgery
Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week
Andra namn:
  • RAD-001
Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Proportion of Patients Who Are P0 (i.e., no Clinically Detectable Tumor in the Pathologic Specimen) at Surgery
Tidsram: 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.
After 8 weeks of therapy at the time of prostatectomy
Toxicity Profile of Each Dose (Number of Patients With Worst Grade Toxicity)
Tidsram: 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)
at daily dose for 8 weeks

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Change in PSA
Tidsram: 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.
Up to 16 weeks after start of study

Andra resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Effect of Treatment on Biological and Molecular Markers
Tidsram: After 8 weeks of therapy
Immunohistochemical Staining of Cellular and Molecular Markers in Prostate Tumor Tissue
After 8 weeks of therapy

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Utredare

  • Huvudutredare: Jorge A. Garcia, MD, Case Comprehensive Cancer Center

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 september 2007

Primärt slutförande (Faktisk)

1 juli 2011

Avslutad studie (Faktisk)

1 augusti 2011

Studieregistreringsdatum

Först inskickad

5 september 2007

Först inskickad som uppfyllde QC-kriterierna

5 september 2007

Första postat (Uppskatta)

10 september 2007

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

6 december 2018

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

14 november 2018

Senast verifierad

1 november 2018

Mer information

Termer relaterade till denna studie

Andra studie-ID-nummer

  • CASE21806
  • P30CA043703 (U.S.S. NIH-anslag/kontrakt)
  • CASE-21806 (Annan identifierare: Case Comprehensive Cancer Center)
  • CASE-21806-CC256 (Annan identifierare: Cancer Center IRB)

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Nej

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

produkt tillverkad i och exporterad från U.S.A.

Nej

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Kliniska prövningar på Everolimus

3
Prenumerera