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Prostatic NeoplasmsPhase 1NCT00032825

Ketoconazole Plus Docetaxel to Treat Prostate Cancer

A Phase 1 study testing Ketaconazole and Docetaxel in people with Prostatic Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will determine the maximum dose of docetaxel that can be given safely in combination with ketoconazole for treating advanced prostate cancer. Docetaxel is approved for the treatment of several other types of cancers; ketoconazole is an approved antifungal medication that is also commonly used in high doses… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostatic Neoplasms
What is being tested?
Ketaconazole and Docetaxel
How many people
674 participants
Where
1 siteUnited States
Study dates
19 Mar 2002to 13 Jun 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histopathological documentation of prostate cancer confirmed in the Pathology Department of the Clinical Center at the National Institutes of Health or the National Naval Medical Center prior to starting this study. Patients whose pathology specimens are no longer available may be enrolled in the trial, if the patient has a clinical course consistent with prostate cancer and pathologic documentation of the diagnosis.
  • Patients must have metastatic progressive androgen-independent prostate cancer (progressive prostate cancer while continuing to receive hormonal ablation, such as that of an LHRH agonist) documented prior to entry. Progression must be documented by at least one of the following parameters:
  • Two consecutively rising PSA levels, separated by at least one week, with at least one measurement that is 50% above the nadir reached after the last therapeutic maneuver (as long as the measurement is 5 ng/ml or greater); and/or,
  • At least one new metastatic deposit on Tc-99 bone scintigraphy; and/or,
  • Progression of soft tissue metastases as measured by appropriate modalities (i.e., imaging, palpation):
  • Development of new area of malignant disease (measurable or non-measurable);
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  • Measurable disease progression by RECIST criteria;
  • At least 4 weeks off of flutamide and 6 weeks off of bicultamide and nilutamide.
  • Patients who have not undergone surgical castration must continue treatment with an LHRH agonist. If for some reason the LHRH agonist has been discontinued prior to entry on the study, then it should be reinstituted and disease progression must be documented.
  • Patients must have a life expectancy of more than 3 months.
  • Patients must have a performance status of 0 to 2 according to the ECOG criteria.
  • Patients must have recovered from any acute toxicity related to prior therapy, including surgery.
  • Hematological eligibility parameters (within 2 weeks before starting therapy):
  • Granulocyte count greater than or equal to 1,500/mm(3)
  • Platelet count greater than or equal to 100,000/mm(3)
  • Biochemical eligibility parameters (within 2 weeks before starting therapy):
  • If the creatinine is greater than 1.5 mg/dl, a 24 hour urine collection must be obtained, and measured creatinine clearance must be at least 40 mL/min.
  • Hepatic function: Hepatic: Bilirubin less than 1.0 mg/dl, AST and ALT less than 2.5 times upper limit of normal. If the alkaline phosphatase is greater than 2.5 times the upper limit of normal, it must be fractionated and the hepatic alkaline phosphatase should be less than 2.5 times the upper limit of normal.
  • Hormonal profile for patients with prostate cancer
  • 1. All patients who have not undergone surgical castration must have a serum testosterone under 50 ng/ml and continue on their GnRh agonist.
  • Patients must not have other active malignancies (within the past two years with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder).
  • Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment), New York Heart Assoc. class II-IV congestive heart failure are not eligible.
  • Patients must be able to understand and sign an informed consent form.
  • Patients must be willing to travel from their home to the NIH for follow-up visits.
  • Patients must be greater than or equal to 18 years of age.
  • Must be able to ingest oral medications to be eligible.

Who cannot join

  • Patients with brain metastases will not be eligible.
  • Patients who have received strontium or samarium will not be eligible.
  • HIV-positive patients receiving combination anti-retroviral therapy will be excluded because of possible pharmacokinetic interactions with ketoconazole, docetaxel or other agents administered during the study. In fact, ketoconazole has been found to increase the toxic effects of several protease inhibitors by affecting CYP3A4 activity.
  • Patients on theophylline will be excluded.
  • Patients who are receiving cisapride will be excluded.
  • Patients who are receiving HMG-CoA inhibitors (lovastatin, atorvastatin, simvastatin, pravastatin and cerivastatin)
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  • Patients currently taking known inhibitors and/or inducers of CYP3A4; patients taking known substrates of CYP3A4 will be evaluated by the primary investigator.
  • Patients who are receiving terfenadine, midazolam, triazolam, alprazolam, astemizole, loratadine, rifampin, isoniazid, dofetilide, pimozide, sirolimus or erythromycin will be excluded.
  • Because gastric acidity is necessary for the dissolution and absorption of ketoconazole, concomitant administration of drugs which decrease gastric acid output or increase gastric pH (e.g., antacids, cimetidine, ranitidine, antimuscarinics, omeprazole, and lansoprazole) may decrease absorption and thus will be prohibited.
  • Patients requiring warfarin will be excluded.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Phase I Trial of High Dose Ketoconazole Plus Weekly Docetaxel in Metastatic Androgen Independent Prostate Cancer

This study will determine the maximum dose of docetaxel that can be given safely in combination with ketoconazole for treating advanced prostate cancer. Docetaxel is approved for the treatment of several other types of cancers; ketoconazole is an approved antifungal medication that is also commonly used in high doses to treat prostate cancer.

Patients 18 years of age and older with advanced prostate cancer that does not respond to hormone therapy may be eligible for this study. Candidates will be screened with blood tests to evaluate liver, kidney and other organ function and with x-rays, scans, or other imaging tests to determine the extent of disease.

Read more

Participants will take the following medications:

  • Docetaxel daily, infused through a vein over 30 minutes, in 4-week cycles-3 consecutive weeks of drug followed by one week of rest
  • Dexamethasone, 12 hours and 1 hour before and 12 hours after docetaxel infusions to help prevent fluid retention caused by the docetaxel
  • Ketoconazole, 3 times a day
  • Hydrocortisone, twice a day to replace a loss of natural steroids caused by the ketoconazole

Patients will be hospitalized 1 to 2 days each for the first and second doses of docetaxel to allow for frequent blood draws to measure blood levels of the drug. Ketoconazole will be started about 2 weeks after the first dose of docetaxel and the second dose of docetaxel will be given 2 days after that. In order to determine the maximum tolerated dose of docetaxel, the first few patients in the study will be given a low dose of the drug, and subsequent patients will get increasingly higher doses until unacceptable side effects occur. Because prostate cancer cells may grow if exposed to testosterone, patients may have to have their testosterone production suppressed either surgically (removal of the testicles) or medically with an injection of leuprolide or goserelin, which are luteinizing hormone-release hormone agonists that reduce the amount of testosterone.

Imaging studies, such as x-rays, bone scans or computed tomography (CT) scans, will be done about every 3 months to examine how the tumor is responding to therapy. After six treatment cycles, patients will have monthly chest x-rays to check for fluid around the lining of the lungs, which may occur as a result of docetaxel therapy.

Treatment is expected to continue for at least 3 to 6 months, although this time could be shortened or extended depending on the tumor response to therapy or side effects of the drugs. Patients who do not experience bad side effects and whose tumor does not grow during the first 3 treatment cycles will continue treatment; those who experience unacceptable side effects will be taken off the study.

...

Read the detailed description

High dose ketoconazole and weekly docetaxel have both been shown to have activity against androgen independent prostate cancer (AIPC). We have demonstrated synergy in prostate cancer in an in vitro model. This is an open label phase I study of high-dose ketoconazole plus weekly docetaxel in patients with metastatic AIPC. The primary objective of this study will be to determine the side effect profile of ketoconazole when combined with weekly docetaxel therapy and determine the maximum tolerated dose (MTD) and a recommended phase II dose (RPIID) of docetaxel when combined with high dose ketoconazole. Since ketoconazole may alter the metabolism of docetaxel, this study will evaluate potential drug interactions and adverse events between these two agents. Ketoconazole dose will be 600mg per day (given 200 mg, three times a day), plus 30mg of hydrocortisone (20mg in the morning and 10mg in the evening), plus docetaxel 10-43 mg/m(2) in a dose escalation, repeated in 28-day cycles, comprising weekly treatments for three consecutive weeks followed by one week off. Each patient will be evaluated every four weeks for the duration of the study.

Being tested
Ketaconazole, Docetaxel
Keywords
Combination, Microtubule, Hormonal, Chemotherapy, Pharmacokinetics, Prostate Cancer, Prostate
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Apr 2002 (estimated)
  2. Study start19 Mar 2002
  3. Study completion13 Jun 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Enrolment
674 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00032825
Sponsor's protocol ID
020149
Other IDs
02-C-0149
Status last verified
4 May 2012
First submitted
3 Apr 2002
Last updated
21 Nov 2019
Results posted
No

Publications

  • Bissery MC, Guenard D, Gueritte-Voegelein F, Lavelle F. Experimental antitumor activity of taxotere (RP 56976, NSC 628503), a taxol analogue. Cancer Res. 1991 Sep 15;51(18):4845-52.

    PubMed 1680023

  • Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr FA, Blumenstein BA, Davis MA, Goodman PJ. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989 Aug 17;321(7):419-24. doi: 10.1056/NEJM198908173210702.

    PubMed 2503724

  • Bubley GJ, Carducci M, Dahut W, Dawson N, Daliani D, Eisenberger M, Figg WD, Freidlin B, Halabi S, Hudes G, Hussain M, Kaplan R, Myers C, Oh W, Petrylak DP, Reed E, Roth B, Sartor O, Scher H, Simons J, Sinibaldi V, Small EJ, Smith MR, Trump DL, Wilding G, et al. Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol. 1999 Nov;17(11):3461-7. doi: 10.1200/JCO.1999.17.11.3461.

    PubMed 10550143

  • Sissung TM, Danesi R, Kirkland CT, Baum CE, Ockers SB, Stein EV, Venzon D, Price DK, Figg WD. Estrogen receptor alpha and aromatase polymorphisms affect risk, prognosis, and therapeutic outcome in men with castration-resistant prostate cancer treated with docetaxel-based therapy. J Clin Endocrinol Metab. 2011 Feb;96(2):E368-72. doi: 10.1210/jc.2010-2070. Epub 2010 Nov 24.

    PubMed 21106711

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ketaconazole and Docetaxel in people with Prostatic Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00032825, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2019.

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