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Neoadjuvant Dasatinib Plus LHRH Analogue Therapy in High-Risk Localized Prostate Cancer
This study is currently recruiting participants.
Verified by Hoosier Oncology Group, March 2009
First Received: March 11, 2009   No Changes Posted
Sponsors and Collaborators: Hoosier Oncology Group
Bristol-Myers Squibb
Information provided by: Hoosier Oncology Group
ClinicalTrials.gov Identifier: NCT00860158
  Purpose

This trial will investigate the activity of dasatinib plus LHRH analogue therapy in high-risk localized prostate cancer.


Condition Intervention Phase
Prostate Cancer
Drug: Dasatinib
Drug: Leuprolide Acetate (LHRH Analogue)
Procedure: Radical Prostatectomy
Phase II

MedlinePlus related topics: Cancer Prostate Cancer
Drug Information available for: Gonadorelin Gonadorelin hydrochloride Leuprolide Leuprolide acetate Dasatinib LH-RH
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase II Study of Neoadjuvant Dasatinib Plus LHRH Analogue Therapy in High-Risk Localized Prostate Cancer

Further study details as provided by Hoosier Oncology Group:

Primary Outcome Measures:
  • To estimate the pathologic complete response (pCR) rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To estimate partial pathologic responses (pPR) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To estimate PSA response rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To estimate progression free survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To evaluate the impact of dasatinib plus LHRH on expression of selected biomarkers [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To estimate safety and tolerability of LHRH plus dasatinib [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 39
Study Start Date: March 2009
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Neoadjuvant dasatinib plus leuprolide acetate followed by radical prostatectomy
Drug: Dasatinib
Dasatinib 100 mg administered once daily per oral route for 28 consecutive days
Drug: Leuprolide Acetate (LHRH Analogue)
Leuprolide acetate 7.5 mg administered subcutaneously on day 1 every 28 days (+ 7 days).
Procedure: Radical Prostatectomy
Radical prostatectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered dasatinib dose.

Detailed Description:

OUTLINE: This is a multi-center study.

  • Dasatinib -100 mg administered once daily per oral route for 28 consecutive days.
  • Leuprolide acetate - 7.5 mg administered subcutaneously on day 1 every 28 days (+ 7 days).

The 28 days of dasatinib and leuprolide injection (plus the time required to recover from toxicity if encountered) is defined as a cycle. Patients will be treated for up to a maximum of 3 cycles of dasatinib and leuprolide acetate.

Radical Prostatectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery.

ECOG performance status 0 or 1

Hematopoietic:

  • Hemoglobin (Hgb) ≥ 8.0 g/dL
  • Platelets ≥ 100 K/mm3
  • Absolute neutrophil count (ANC) ≥ 1.0 K/mm3

Hepatic:

  • Total bilirubin < 2.0 X ULN
  • Aspartate aminotransferase (AST) < 2.5 X ULN
  • Alanine aminotransferase (ALT) < 2.5 X ULN

Renal:

  • Calculated creatinine clearance of ≥ 60 cc/min using the Cockcroft-Gault formula

Cardiovascular:

  • No uncontrolled angina, congestive heart failure or MI within 6 months prior to registration for protocol therapy.
  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate.
  • Clinical stage T1-T3a disease.
  • Must be willing to have a tumor biopsy, if previous tumor tissue unavailable for tumor marker analysis.
  • Kattan pre-operative nomogram-predicted (based on stage, PSA and Gleason score) 5-year risk of recurrence-free survival of 80% or less
  • Must be deemed eligible for radical prostatectomy.
  • Must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 6 weeks after treatment discontinuation.
  • Written informed consent and HIPAA authorization for release of personal health information.
  • Age > 18 years at the time of consent.

Exclusion Criteria:

  • No evidence of regional, lymph node or distant metastasis on clinical or radiological assessments. All baseline radiology studies must be performed within 28 days prior to registration for protocol therapy.
  • No prior malignancy in the past 2 years except for basal cell and squamous cell carcinoma of the skin. Other cancers with low potential for metastasis, such as in situ cancers (e.g., Grade 1, TA TCC (low grade superficial bladder cancer), and colonic polyp with focus of adenocarcinoma) can be enrolled after approval from the Sponsor Investigator.
  • No prior hormonal therapy with the exception of oral 5-alpha-reductase inhibitors (finasteride, dutasteride, etc.). Patients who have received prior oral anti-androgen therapies (bicalutamide, flutamide, nilutamide, etc.), prior LHRH agonist therapy (leuprolide, goserelin acetate, etc.), or prior orchiectomy are ineligible.
  • No prior systemic chemotherapy or radiotherapy for prostate cancer is allowed. Transurethral resection of the prostate for benign prostatic hypertrophy (BPH) and oral alpha-blockers (terazosin, tamsulosin, doxazosin) are permitted.
  • No history of hemorrhage or thrombotic events (cerebrovascular accident, deep vein thrombosis, pulmonary embolism, etc.) within 6 months prior to registration for protocol therapy.
  • No history of diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
  • No history of diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) of registration on protocol therapy.
  • No history of ongoing or recent (≤ 3 months of registration on protocol therapy) significant gastrointestinal bleeding
  • No ongoing anti-coagulation and/or anti-platelet therapies allowed.
  • No unresolved pleural or pericardial effusion of any grade within 3 months of registration for protocol therapy.
  • No uncontrolled angina, congestive heart failure or MI within 6 months prior to registration for protocol therapy.
  • No diagnosed congenital long QT syndrome.
  • No history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes).
  • No prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)
  • Following medications must be discontinued at least 7 days prior to registration for protocol therapy and be withheld for the duration of dasatinib therapy:
  • Drugs that are generally accepted to have a risk of causing Torsades de Pointes
  • Patient must not be receiving any prohibited CYP3A4 inhibitors /inducers/ substrates
  • Anti-coagulation and/or anti-platelet therapies - to avoid potential bleeding risks.
  • No major surgical procedure, open biopsy, or significant trauma within 28 days prior to registration for protocol therapy.
  • Ability to comply with study and/or follow-up procedures and requirements.
  • No treatment with any investigational agent for any medical condition within 28 days prior to registration for protocol therapy.
  • No clinically significant infections or any other condition which, in the investigator's opinion, deems the patient an unsuitable candidate to receive the study drug.
  • Ability to take oral medication (dasatinib must be swallowed whole).
  • No known history of hypokalemia that cannot be corrected prior to registration on protocol therapy.
  • No known history of hypomagnesemia that cannot be corrected prior to registration on protocol therapy.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00860158

Contacts
Contact: Noah Hahn, M.D. 317.274.0920 nhahn@iupui.edu
Contact: Peter Pletcher, M.B.A. 317.921.2050 gegould@iupui.edu

Locations
United States, Indiana
Indiana University Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Noah Hahn, M.D.     317-278-6942     nhahn@iupui.edu    
Contact: Kerry Bridges     317-274-2552     kdbridge@iupui.edu    
Sponsors and Collaborators
Hoosier Oncology Group
Bristol-Myers Squibb
Investigators
Study Chair: Noah Hahn, M.D. Hoosier Oncology Group
  More Information

Additional Information:
No publications provided

Responsible Party: Hoosier Oncology Group ( Noah Hahn, M.D. )
Study ID Numbers: HOG GU07-124
Study First Received: March 11, 2009
Last Updated: March 11, 2009
ClinicalTrials.gov Identifier: NCT00860158     History of Changes
Health Authority: United States: Food and Drug Administration

Study placed in the following topic categories:
Antineoplastic Agents, Hormonal
Prostatic Diseases
Genital Neoplasms, Male
Leuprolide
Dasatinib
Urogenital Neoplasms
Genital Diseases, Male
Protein Kinase Inhibitors
Prostatic Neoplasms

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Genital Neoplasms, Male
Prostatic Diseases
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Urogenital Neoplasms
Reproductive Control Agents
Genital Diseases, Male
Protein Kinase Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Leuprolide
Fertility Agents, Female
Dasatinib
Therapeutic Uses
Fertility Agents
Prostatic Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009