Ketoconazole, Hydrocortisone, Dutasteride and Lapatinib (KHAD-L) in Prostate Cancer (KHLAD)

This study is currently recruiting participants.
Verified December 2013 by Dana-Farber Cancer Institute
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Massachusetts General Hospital
Prostate Cancer Foundation Clinical Research Consortium
GlaxoSmithKline
Information provided by (Responsible Party):
Dana-Farber Cancer Institute ( Beth Israel Deaconess Medical Center )
ClinicalTrials.gov Identifier:
NCT00953576
First received: August 4, 2009
Last updated: December 18, 2013
Last verified: December 2013

August 4, 2009
December 18, 2013
August 2009
August 2014   (final data collection date for primary outcome measure)
  • Assess the safety of combination therapy of ketoconazole, hydrocortisone, dutasteride and lapatinib [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Establish the MTD of KHAD plus lapatinib [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The goal of the study was to determine what dose of lapatinib was safe and tolerable in combination with ketoconazole
  • Determine the pharmacokinetics of lapatinib when used in combination with KHAD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Assess the safety of combination therapy of ketoconazole, hydrocortisone, dutasteride and lapatanib [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Establish the MTD of KHAD plus lapatanib [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Determine the pharmacokinetics of lapatanib when used in combination with KHAD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00953576 on ClinicalTrials.gov Archive Site
Not Provided
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Ketoconazole, Hydrocortisone, Dutasteride and Lapatinib (KHAD-L) in Prostate Cancer
A Phase I/II Trial of Ketoconazole, Hydrocortisone, Dutasteride and Lapatinib (KHAD-L) in Castration Resistant Prostate Cancer With Pre- and Post-therapy Tumor Biopsies

The purpose of this research study is to determine the safety of giving ketoconazole, hydrocortisone and dutasteride (KHAD) with lapatinib. The investigators believe that there is evidence in castrate resistant prostate cancer that two growth factor receptors (EGFr and Her 2 /neu )are increased in prostate cancer cells. Both these receptors are turned off by the drug lapatinib. By adding lapatinib to this trial, the investigators hope that the investigators can turn off the signaling from the receptors and therefore make the participant's cancer more responsive to KHAD treatment.

  • For the initial four weeks of the study, participants will receive the drugs ketoconazole, dutasteride and hydrocortisone daily (KHAD treatment). Ketoconazole will be taken orally three times a day, hydrocortisone will be taken orally twice a day and dutasteride will be taken orally once a day.
  • During the 3rd or 4th week of KHAD treatment participants will undergo a CT-guided bone biopsy.
  • After completion of 4 weeks on KHAD treatment, participants will start taking lapatinib along with KHAD starting from week 5. Lapatinib is taken orally once a day.
  • During the 3rd or 4th week of KHAD and Lapatinib (KHLAD) treatment, participants will undergo a CT-guided bone biopsy.
Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • Drug: ketoconazole
    Taken orally three times daily
  • Drug: hydrocortisone
    Taken orally twice daily
  • Drug: dutasteride
    Taken orally once a day
  • Drug: lapatinib
    Starting week 5, taken orally once daily
Experimental: KHAD+L
Ketoconazole, Hydrocortisone, Dutasteride and Lapatinib
Interventions:
  • Drug: ketoconazole
  • Drug: hydrocortisone
  • Drug: dutasteride
  • Drug: lapatinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
24
Not Provided
August 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with CRPC with metastatic bone disease. At least one site of metastatic disease must be amenable to a needle biopsy. Bone sites include lumbar vertebrae, pelvic bones and long bones. Excluded sites are thoracic, cervical vertebrae, skull and rib lesions
  • Patients may have had a number of previous hormonal therapies including ketoconazole and abiraterone, provided these were discontinued >3 months before starting the trial
  • Patients may have had any number of previous cytotoxic therapies
  • Castrate resistant disease as defined by PSA working group. Patients must have a rise in PSA on two successive determinations at least one week apart and PSA levels 5ng/ml or greater and testosterone levels <50
  • Adequate renal, hepatic and bone marrow function as outlined in protocol
  • PTT< 60, INR <1.5NL unless on warfarin therapy
  • > 6 month life expectancy
  • At least a 4 week interval from previous treatment other than LHRH analog and bisphosphonates. Patients on bicalutamide must have discontinued this medication for at least 6 weeks to be eligible
  • Patients receiving bisphosphonate can be maintained on this therapy
  • No major surgery or radiation therapy within 4 weeks
  • No strontium-89 or samarium-153 therapy within 4 weeks
  • ECG showing normal QT interval
  • No thromboembolism in past 6 months
  • Age > 18 years
  • Investigator must check current patient medications against the list of CYP3A4 inhibitors and inducers prior to registration
  • Echocardiogram or MUGA demonstrating ejection fraction within institutional normal limits

Exclusion Criteria:

  • No previous therapy with lapatinib
  • No previous therapy with ketoconazole within 3 months of starting trial
  • The use of complementary therapy directed at prostate cancer treatment excluding the following: green tea, commercial multivitamin preparations. Vitamin B complex, C, D, E and multivitamins are permitted if these are being taken at less than 3 times the RDA
  • The concomitant use of drugs known to be narrow therapeutic index CYP3A4 substrates are excluded
  • Drugs that are sensitive to CYP3A4 substrates are excluded
  • Patients taking drugs that may further prolong QT intervals and present a known risk for Torsades de Pointes are excluded.
  • Patients who have alcohol or drug dependence currently or in the last 6 months are excluded from this study
  • Any other events, other than those defined above, in the opinion of the investigator, may make the patient ineligible for this trial
  • No contraindication to biopsy such as bleeding disorders. Patients on anticoagulants such as warfarin must be able to safely stop the drug for a three-day period. Patients may not go on heparin during this time
  • No active malignancy other than skin cancer or superficial bladder cancer
  • Cardiac disease: congestive heart failure > class II NYHA. Patients must no have unstable angina or new onset angina or myocardial infarction within the past 6 months. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. Patients must have an ejection fraction within normal limits at the enrolling institution based on an echocardiogram
  • Uncontrolled hypertension defined as sustained BP > 160 and diastolic > 100 despite optimal medical management
  • Known HIV or chronic Hep B or C
  • Thrombolic or embolic events such as CVA within the last 6 months
  • Pulmonary hemorrhage or any bleeding event CTCAE Grade 2 or greater within 6 months of first dose of study drug of KHAD
  • Serious non-healing wound, ulcer, or bone fracture
  • Evidence of history of bleeding diathesis or coagulopathy
  • Major surgery or significant traumatic injury within 4 weeks of first study drug of KHAD
Male
18 Years and older
No
Contact: Glenn Bubley, MD 617-735-2062
United States
 
NCT00953576
08-374
Yes
Dana-Farber Cancer Institute ( Beth Israel Deaconess Medical Center )
Beth Israel Deaconess Medical Center
  • Dana-Farber Cancer Institute
  • Brigham and Women's Hospital
  • Massachusetts General Hospital
  • Prostate Cancer Foundation Clinical Research Consortium
  • GlaxoSmithKline
Principal Investigator: Glenn Bubley, MD Beth Israel Deaconess Medical Center
Dana-Farber Cancer Institute
December 2013

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