Ketoconazole With or Without Alendronate Sodium in Treating Patients With Metastatic Prostate Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2004 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00019695
First received: March 1, 2007
Last updated: NA
Last verified: March 2004
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Stage IV Prostate Cancer
Bone Metastases
Adenocarcinoma of the Prostate
Recurrent Prostate Cancer
Drug: alendronate sodium
Drug: ketoconazole
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: March 1999
Detailed Description:

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.

PROJECTED ACCRUAL:

A total of 72 patients (36 per arm) will be accrued for this study within 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Criteria

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00019695

Locations
United States, Maryland
Medicine Branch
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Study Chair: William D. Figg National Cancer Institute (NCI)
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00019695     History of Changes
Obsolete Identifiers: NCT00001802
Other Study ID Numbers: CDR0000066964, NCI-99-C-0052
Study First Received: March 1, 2007
Last Updated: March 1, 2007
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the prostate
adult solid tumor
body system/site cancer
bone metastases
cancer
cellular diagnosis, prostate cancer
genetic condition
male reproductive cancer
metastatic cancer
prostate cancer
recurrent prostate cancer
site, metastatic cancer
solid tumor
stage IV prostate cancer
stage, prostate cancer
unclassified/other cancer

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Neoplasm Metastasis
Bone Neoplasms
Bone Marrow Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Neoplastic Processes
Pathologic Processes
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases
Ketoconazole
Alendronate
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014