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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2009 by Mount Sinai School of Medicine.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT00900744
First received: May 11, 2009
Last updated: May 12, 2009
Last verified: May 2009
  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 Phase
Breast Cancer
Drug: Tamoxifen
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Specific human 2D6 variants measurement(s) or observation(s) [ Time Frame: every two weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: January 2009
Estimated Study Completion Date: January 2010
Estimated Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Tamoxifen Drug: Tamoxifen
20 mg daily

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.

We plan to examine endoxifen and 4-OH-Tam as a function of the tamoxifen dose in patients with a genetic CYP2D6 polymorphism. We 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, we will examine other genes that may influence the metabolism of medications.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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), Biliribin 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00900744

Contacts
Contact: Annie Zuo, MSc 212-842-7314 qian.zuo@mssm.edu
Contact: Marisa Cortese 212-824-7319

Locations
United States, New York
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Sponsors and Collaborators
Mount Sinai School of Medicine
Investigators
Principal Investigator: Myra Barginear, MD Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Myra Barginear, MD Prinicipal Investigator, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT00900744     History of Changes
Other Study ID Numbers: GCO# 08-1373
Study First Received: May 11, 2009
Last Updated: May 12, 2009
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Tamoxifen
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Bone Density Conservation Agents
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Selective Estrogen Receptor Modulators
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014