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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00900744
First Posted: May 13, 2009
Last Update Posted: August 25, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Icahn School of Medicine at Mount Sinai
  Purpose
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.

Condition Intervention
Breast Cancer Drug: Tamoxifen

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Pilot Study of Varying Doses of Tamoxifen in the Setting of Genetic Polymorphisms of CYP2D6

Resource links provided by NLM:


Further study details as provided by Icahn School of Medicine at Mount Sinai:

Primary Outcome Measures:
  • Specific human 2D6 variants measurement(s) or observation(s) [ Time Frame: every two weeks ]

Enrollment: 121
Study Start Date: January 2009
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Tamoxifen
20mg daily
Drug: Tamoxifen
20 mg daily
Other Name: Nolvadex®

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
patients with a genetic CYP2D6 polymorphism
Criteria

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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00900744


Locations
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
Investigators
Principal Investigator: George Raptis, MD Icahn School of Medicine at Mount Sinai
  More Information

Responsible Party: Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT00900744     History of Changes
Other Study ID Numbers: GCO 08-1373
IF#1248430
HSM10-00403
First Submitted: May 11, 2009
First Posted: May 13, 2009
Last Update Posted: August 25, 2017
Last Verified: August 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Icahn School of Medicine at Mount Sinai:
Tamoxifen
Breast Cancer

Additional relevant MeSH terms:
Tamoxifen
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents