Ketoconazole With or Without Alendronate Sodium in Treating Patients With Metastatic Prostate Cancer
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Stage IV Prostate Cancer; Bone Metastases; Adenocarcinoma of the Prostate; Recurrent Prostate Cancer
Intervention: alendronate sodium (Drug); ketoconazole (Drug)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: National Cancer Institute (NCI)
Official(s) and/or principal investigator(s):
William D. Figg, Study Chair, Affiliation: National Cancer Institute (NCI)
RATIONALE: Ketoconazole may suppress the production of hormones and may interfere in the
growth of prostate cancer cells. Alendronate sodium may be effective in preventing bone
metastases and bone pain associated with prostate cancer. It is not known if ketoconazole is
more effective with or without alendronate sodium.
PURPOSE: Randomized phase II trial to study the effectiveness of ketoconazole with or without
alendronate sodium in treating patients who have metastatic prostate cancer.
Official title: Phase II Randomized Study of High-Dose Ketoconazole With or Without Alendronate Sodium in Patients With Androgen-Independent Metastastic Adenocarinoma of the Prostate
Study design: Treatment
OBJECTIVES: I. Determine whether there is any evidence that ketoconazole plus alendronate
sodium produces acceptable disease responses as compared with ketoconazole alone in patients
with androgen-independent metastatic adenocarcinoma of the prostate.
II. Characterize the pharmacokinetics/pharmacodynamics and assess the bone marrow
concentrations of both agents.
III. Assess matrix metalloproteinase (MMP) inhibition potential of alendronate sodium by
monitoring markers of angiogenesis, MMP breakdown, and changes in hydroxyproline.
PROTOCOL OUTLINE: This is a randomized, open-label study. Patients are randomized to one of
two treatment arms.
Arm I: Patients receive a single oral dose of ketoconazole on day 1. Patients begin taking
ketoconazole 3 times per day on day 8.
Arm II: Patients receive a single oral dose of alendronate sodium on day 1 and a single oral
dose of ketoconazole on day 3. Patients begin taking alendronate sodium once every morning
and ketoconazole 3 times per day on day 8.
Treatment continues on both arms in the absence of unacceptable toxicity or disease
progression. Patients who experience a clinical complete remission (CR) receive treatment
for an additional 60 days beyond documentation of a clinical CR.
Patients are followed every 2 months.
A total of 72 patients (36 per arm) will be accrued for this study within 3 years.
Minimum age: 18 Years.
Maximum age: N/A.
PROTOCOL ENTRY CRITERIA:
- -Disease Characteristics-- Histologically confirmed adenocarcinoma of the prostate
Androgen independent with at least 1 bone lesion that is felt to be associated with
metastatic disease Refractory disease must be demonstrated after the withdrawal of
flutamide, nilutamide, bicalutamide, or any other antiandrogen Clinically progressive
disease for at least 1 month documented by rising PSA levels, at least 1 new metastatic
deposit on Tc-99 bone scintigraphy, increasing measurable disease, or new areas of
malignant disease Patients with PSA-negative disease (i. e., PSA less than 10 ng/mL) must
have positive CT scans of soft tissue disease that can be used for disease staging, bone
scan, or some other form of documentable disease progression (i. e., rising carcinoembryonic
antigen, prostatic acid phosphatase) Testosterone in the range expected for castrated males
No brain metastases or primary CNS malignancies No unresolved acute local complications
that require urgent local medical therapy (such as severe bone pain, spinal cord
compression, or urinary flow obstruction) - -Prior/Concurrent Therapy-- Biologic therapy:
Not specified Chemotherapy: No prior ketoconazole for prostate cancer Endocrine therapy:
See Disease Characteristics Treatment with LHRH agonist must continue for those patients
who have not undergone surgical castration If LHRH agonist has been discontinued, it must
be reinstituted with documented disease progression At least 4 weeks since prior hormonal
therapy other than LHRH agonist and recovered Radiotherapy: Prior radiotherapy to the
prostate allowed At least 4 weeks since prior radiotherapy and recovered Surgery: Prior
radical prostatectomy allowed At least 4 weeks since prior surgery and recovered Other: At
least 4 weeks since other prior anti-cancer therapy and recovered No prior transfusion with
strontium chloride Sr 89 and/or samarium Sm 153 lexidronam pentasodium No concurrent
phenytoin, theophylline, cisapride, triazolam, astemizole, loratadine, rifampin, isoniazid,
erythromycin, terfenadine, midazolam, alprazolam, atorvastatin calcium, cerivastatin
sodium, dofetilide, lovastatin, pimozide, simvastatin, or sirolimus No concurrent drugs
that decrease gastric acid output or increase gastric pH (e. g., antacids, cimetidine,
ranitidine, or antimuscarinics) No concurrent warfarin - -Patient Characteristics-- Age: 18
and over Performance status: ECOG 0-2 Life expectancy: Greater than 3 months Hematopoietic:
Granulocyte count at least 1,000/mm3 Hemoglobin at least 8. 0 g/dL (pretreatment transfusion
allowed, provided hemoglobin is maintained for more than 30 days without additional
transfusions and/or an active source of bleeding is identified and treated) Platelet count
at least 75,000/mm3 Hepatic: Acute care panel (i. e., electrolytes, BUN) and urinalysis
normal Bilirubin no greater than 1. 2 mg/dL ALT less than 2. 5 times upper limit of normal
AST less than 2. 5 times normal Renal: Creatinine no greater than 1. 5 mg/dL and no
proteinuria present OR Creatinine clearance greater than 40 mL/min and proteinuria less
than 500 mg/day (proteinuria not an exclusion for patients with stents in place)
Cardiovascular: No history of unstable or newly diagnosed angina pectoris No myocardial
infarction within the past 6 months No New York Heart Association class II-IV congestive
heart failure Pulmonary: No chronic obstructive lung disease requiring oxygen therapy
Neurologic: No uncontrolled seizure activity No history of seizures within the past 10
years Other: No other prior malignancies within the past 2 years except nonmelanoma skin
cancer or carcinoma in situ of the bladder No other life-threatening illnesses No untreated
infection HIV negative Willingness to travel from home to NIH for follow-up visits
Locations and Contacts
Medicine Branch, Bethesda, Maryland 20892, United States
Starting date: March 1999
Last updated: March 1, 2007