Ketoconazole, Hydrocortisone, Dutasteride and Lapatinib (KHAD-L) in Prostate Cancer
Information source: Dana-Farber Cancer Institute
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Prostate Cancer
Intervention: ketoconazole (Drug); hydrocortisone (Drug); dutasteride (Drug); lapatinib (Drug)
Phase: Phase 1/Phase 2
Status: Active, not recruiting
Sponsored by: Beth Israel Deaconess Medical Center Official(s) and/or principal investigator(s): Glenn Bubley, MD, Principal Investigator, Affiliation: Beth Israel Deaconess Medical Center
Summary
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.
Clinical Details
Official title: 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
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Assess the safety of combination therapy of ketoconazole, hydrocortisone, dutasteride and lapatinibEstablish the MTD of KHAD plus lapatinib Determine the pharmacokinetics of lapatinib when used in combination with KHAD
Detailed description:
- 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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Male.
Criteria:
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
Locations and Contacts
Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, United States
Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States
Additional Information
Starting date: August 2009
Last updated: April 8, 2015
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