A Pilot Study of Varying Doses of Tamoxifen in the Setting of Genetic Polymorphisms of CYP2D6

August 24, 2017 updated by: Icahn School of Medicine at Mount Sinai
The investigators plan to examine endoxifen and 4-OH-Tam as a function of the tamoxifen dose in patients with a genetic CYP2D6 polymorphism. The investigators also plan to investigate other genetic variations in the metabolism of tamoxifen.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Endocrine therapy has proven to be an extremely effective therapy in breast cancer. For women with hormone-receptor-positive tumors, tamoxifen given for as little as two years results in a statistically significant recurrence and survival benefit. The benefits increase as the duration of treatment increase, up to 5 years, so that among women treated for five years, tamoxifen can result in up to a 46 percent annual reduction in the recurrence rate and up to a 28 percent annual reduction in the death rate. This means that about half of the recurrences and more than one fourth of the deaths each year are prevented by tamoxifen treatment. However, despite initial successful responses, many patients on tamoxifen relapse and die from progressive disease. Consequently, tamoxifen resistance remains a major clinical problem in the management of breast cancer.

Tamoxifen is metabolized by cytochrome P450 2D6 (CYP2D6) to the more potent metabolites 4-hydroxy-tamoxifen (4-OH-TAM) and 4-hydroxy-N-desmethyltamoxifen (endoxifen). Variations in the metabolic capacity of this enzyme have shown to be an independent predictor of breast cancer relapse and death. To date, studies have not correlated tamoxifen doses to CYP2D6 genotype status or associated tamoxifen doses to endoxifen and 4-OH-tamoxifen.

The investigators plan to examine endoxifen and 4-OH-Tam as a function of the tamoxifen dose in patients with a genetic CYP2D6 polymorphism. The investigators also plan to investigate other genetic variations in the metabolism of tamoxifen. The possible identification of gene variants that alter tamoxifen's metabolism may improve initial dose selection and therefore optimize treatment outcome in the future.

In addition to examining polymorphisms in CYP2D6, other genes will be examine that may influence the metabolism of medications.

Study Type

Observational

Enrollment (Actual)

121

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

patients with a genetic CYP2D6 polymorphism

Description

Inclusion Criteria:

  • Women taking tamoxifen 20mg a day
  • Tamoxifen use for > 90 days.
  • Use an accepted barrier form of contraception.

Exclusion Criteria:

  • Patients are excluded if they are pregnant or lactating; if pre- menopausal, the patient will have a documented negative pregnancy test and use an accepted barrier form of contraception.
  • Patients are excluded if they have a medical history of Hepatitis B. Hepatitis C or HIV
  • Patients are excluded if they use Tobacco
  • Patients are excluded if they have a medical history of hereditary hemochromatosis

  • Patients are excluded if they have elevated AST (SGOT), ALT (SGPT), Bilirubin or Alkaline Phosphate

    o Defined as greater than 2 1/2 times the upper limit of normal

  • Patients are excluded if they are being treated with chemotherapy

  • Patients are excluded if they are taking any of the following oral medications, as they are potent CYP2D6 inhibitors:

    • Fluoxetine (Prozac)
    • Miconazole (Monistat)
    • Paroxetine (Paxil)
    • Quinidine
    • Ritonavir (Norvir)
    • Atorvastatin (Lipitor)
    • Carvedilol (Coreg)
    • Clarithromycin (Biaxin)
    • Dipyridamole (Persantine)
    • Erythromycin
    • Grapefruit Juice
    • Itraconazole (Sporanox)
    • Ketoconazole
    • Mefloquine
    • Nelfinavir (Viracept)
    • Nicardipine (Cardene)
    • Nilotinib
    • Propranolol (Inderal)
    • Ranolazine (Ranexa)
    • Saquinavir ( Invirase)
    • Verapamil Covera-HS
    • Warfarin (Coumadin)
    • Chlorpromazine (Thorazine)
    • Cinacalcet (Sensipar)
    • Delavirdine (Rescriptor)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Tamoxifen
20mg daily
Drug: Tamoxifen
20 mg daily
Other Names:
  • Nolvadex®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Specific human 2D6 variants measurement(s) or observation(s)
Time Frame: every two weeks
every two weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Icahn School of Medicine at Mount Sinai

Investigators

  • Principal Investigator: George Raptis, MD, Icahn School of Medicine at Mount Sinai

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (ACTUAL)

January 1, 2012

Study Completion (ACTUAL)

January 1, 2012

Study Registration Dates

First Submitted

May 11, 2009

First Submitted That Met QC Criteria

May 12, 2009

First Posted (ESTIMATE)

May 13, 2009

Study Record Updates

Last Update Posted (ACTUAL)

August 25, 2017

Last Update Submitted That Met QC Criteria

August 24, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCO 08-1373
  • IF#1248430
  • HSM10-00403

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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