Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Tamoxifen in Women With Breast Cancer and in Women at High-Risk of Breast Cancer Who Are Receiving Venlafaxine, Citalopram, Escitalopram, Gabapentin, or Sertraline

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs No phase specified Biomarker/Laboratory analysis, Treatment Active 18 and over NCI MAYO-MC0738 MC0738, NCT00667121

Objectives

1. To examine the changes in the plasma concentrations of the hydroxylated metabolite, 4-hydroxy tamoxifen, and endoxifen in women with known or at high risk for developing breast cancer who are receiving selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor therapy comprising venlafaxine, citalopram hydrobromide, escitalopram oxalate, gabapentin, or sertraline hydrochloride for the treatment of hot flashes, depression, or any other medically indicated condition.
2. To evaluate whether genetic variants known to affect the activity of CYP2D6, SULT1A1, and other drug metabolizing enzymes (e.g., UGT’s) involved in the biotransformation of tamoxifen citrate affect the plasma concentrations of the hydroxylated metabolites, 4-hydroxy tamoxifen and endoxifen.

Entry Criteria

Disease Characteristics:

• Meets 1 of the following criteria:
  • Diagnosis of invasive or non-invasive breast cancer
  • At high risk for developing breast cancer



• Has been receiving tamoxifen citrate for at least 4 weeks without any breaks either for the prevention or the adjuvant treatment of invasive or non-invasive breast cancer at a dose of 20 mg/day



• Planning to begin medical therapy with one of the following drugs, as determined by physician:
  • Venlafaxine
  • Citalopram hydrobromide
  • Escitalopram oxalate
  • Sertraline hydrochloride
  • Gabapentin



• Agrees to continue tamoxifen citrate during the proposed minimum study period of 8 weeks



• Known CYP2D6 genotype
  • Not known to be a CYP2D6 poor metabolizer (defined as homozygous for one of the following CYP2D6 null alleles: *3, *4, *5, *6) as determined from the baseline genotype test



• Estrogen receptor-positive disease (for patients with breast cancer)

Prior/Concurrent Therapy:

• See Disease Characteristics
• More than 4 weeks since prior and no concurrent medications that are known to inhibit the CYP2D6 system

Patient Characteristics:

• Menopausal status not specified
• Life expectancy ≥ 16 weeks
• Willing to return to primary site of enrollment for follow-up, including any of the following:
  • Mayo Clinic Rochester
  • Indiana University
  • University of Michigan
  • Johns Hopkins
• No contraindication for venlafaxine, citalopram hydrobromide, escitalopram oxalate, gabapentin, or sertraline hydrochloride

Expected Enrollment

Outcomes

Percent change in plasma concentrations of 4-hydroxy tamoxifen and of endoxifen after ≥ 8 weeks of concurrent administration of tamoxifen citrate and a CYP2D6 inhibitor

Outline

This is a multicenter study.

Patients receive oral tamoxifen citrate and concurrent selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) therapy comprising oral venlafaxine, citalopram hydrobromide, escitalopram oxalate, sertraline hydrochloride, or gabapentin for 8-24 weeks. Treatment continues in the absence of disease progression.

Blood samples are obtained at baseline and after completion of study therapy. Samples are evaluated by pharmacokinetic analysis to determine the effects of SSRI/SNRI study drugs on plasma concentrations of tamoxifen and its metabolites. Plasma levels of tamoxifen citrate, N-desmethyl tamoxifen, 4-OH tamoxifen, and endoxifen are measured using reverse phase high performance liquid chromatography. Blood samples are also analyzed by CYP2D6 genotyping to test for CYP2D6 gene variation (i.e., *3, *4, *6, *10, *17, and *41) in genes that encode tamoxifen-metabolizing enzymes. Additional CYP2D6 alleles, including gene duplication and gene deletion (*5) are assessed.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Matthew Goetz, MD, Protocol chair		Ph: 507-284-4857 Email: goetz.matthew@mayo.edu

U.S.A.
Indiana
	Indianapolis
	Indiana University Melvin and Bren Simon Cancer Center
		Clinical Trials Office - Indiana University Cancer Center	Ph:  317-274-2552
Maryland
	Baltimore
	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
		Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Center at John Hopkins	Ph:  410-955-8804
			Email: jhcccro@jhmi.edu
Michigan
	Ann Arbor
	University of Michigan Comprehensive Cancer Center
		Clinical Trials Office - University of Michigan Comprehensive Cancer Center	Ph:  800-865-1125
Minnesota
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623

Registry Information
Official Title		The Effect of Antidepressants and Gabapentin on Tamoxifen Pharmacokinetics: A Prospective Study
Trial Start Date		2008-03-04
Trial Completion Date		2009-07-31 (estimated)
Registered in ClinicalTrials.gov		NCT00667121
Date Submitted to PDQ		2008-01-16
Information Last Verified		2008-12-28

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