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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Prostate Cancer

Thank you

Trial Information

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

- 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

- 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.

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

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Assess the safety of combination therapy of ketoconazole, hydrocortisone, dutasteride and lapatinib

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Glenn Bubley, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beth Israel Deaconess Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

August 2009

Completion Date:

Related Keywords:

  • Prostate Cancer
  • castration resistant prostate cancer
  • KHAD
  • Prostatic Neoplasms



Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
Dana-Farber Cancer Institute Boston, Massachusetts  02115