4-Hydroxytamoxifen or Tamoxifen Citrate in Treating Women With Newly Diagnosed Ductal Breast Carcinoma in Situ - Full Text View

Sponsor:	Robert H. Lurie Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00952731

Purpose

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. It is not yet known whether topical tamoxifen causes less damage to normal tissue than systemic tamoxifen in treating patients with ductal carcinoma in situ.

PURPOSE: This randomized phase II trial is studying 4-hydroxytamoxifen to see how well it works compared with tamoxifen citrate in treating women with newly diagnosed ductal breast carcinoma in situ.

Condition	Intervention	Phase
Breast Cancer	Drug: 4-hydroxytamoxifen Drug: tamoxifen citrate Other: placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control
Official Title:	Pre-surgical Phase IIb Trial of Transdermal 4-Hydroxytamoxifen vs. Oral Tamoxifen in Women With Duct Carcinoma in Situ of the Breast

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Surgery

Drug Information available for: Tamoxifen Tamoxifen citrate Citric acid Sodium Citrate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Demonstration that once daily topical 4-hydroxytamoxifen (4-OHT) gel application results in a reduction in the Ki-67 labeling index of ductal carcinoma in situ lesions that is not inferior to that seen with oral tamoxifen citrate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Comparison of concentrations of 4-OHT, endoxifen, tamoxifen, its bisphenol metabolite, and estradiol in breast tissue and plasma at the time of surgery [ Designated as safety issue: No ]
CYP2D6 polymorphism status and comparison of drug metabolite levels by polymorphism status [ Designated as safety issue: No ]
Affect of 4-OHT on known tamoxifen-modulated pathways in the breast and serum by IHC and plasma markers [ Designated as safety issue: No ]
Tamoxifen metabolite concentrations and estrogen response markers in nipple aspiration fluid samples from affected and unaffected breast [ Designated as safety issue: No ]
Comparison of incidence of hot flashes at baseline and before surgery [ Designated as safety issue: No ]
Comparison of changes in coagulation related proteins [ Designated as safety issue: No ]
Comparison of Z and E 4-OHT isomers in the plasma [ Designated as safety issue: No ]

Estimated Enrollment:	112
Study Start Date:	October 2009
Estimated Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive oral placebo once daily and apply topical 4-hydroxytamoxifen gel to both breasts daily.	Drug: 4-hydroxytamoxifen Applied topically Other: placebo Given orally or applied topically
Arm II: Active Comparator Patients receive oral tamoxifen citrate once daily and apply topical placebo gel to both breasts daily.	Drug: tamoxifen citrate Given orally Other: placebo Given orally or applied topically

Detailed Description:

OBJECTIVES:

Primary

To demonstrate that 4-hydroxytamoxifen (4-OHT) gel formulation applied once daily topically to the breasts results in a reduction in the Ki-67 labeling index of ductal carcinoma in situ lesions that is not inferior to that seen with oral tamoxifen citrate daily for 6-10 weeks, when comparing the baseline diagnostic core needle biopsy to the therapeutic surgical excision (TSE) sample in women with ductal breast carcinoma in situ.

Secondary

To compare concentrations of 4-OHT, endoxifen, tamoxifen, its bisphenol metabolite, and estradiol in breast adipose tissue and plasma obtained at surgery between the two groups following 6-10 weeks of treatment.
To compare drug metabolite levels between the two groups by CYP2D6 polymorphism status.
To demonstrate that 4-OHT affects known tamoxifen-modulated pathways in the breast and plasma in a similar manner to tamoxifen citrate, using IHC and serum markers.
To evaluate tamoxifen metabolite concentrations and estrogen response markers in nipple aspiration fluid from the unaffected breast in relation to the same metabolites in tissue samples from the affected breast.
To compare the incidence of hot flashes between the two groups at baseline and before TSE.
To compare the changes in coagulation related proteins between the two groups at baseline and before TSE.
To compare E and Z isomers of 4-OHT in the plasma between the two groups before TSE.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center (Northwestern University vs Duke University vs Washington University) and menopausal status (pre- vs postmenopausal). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral placebo once daily and apply topical 4-hydroxytamoxifen gel to both breasts daily.
Arm II: Patients receive oral tamoxifen citrate once daily and apply topical placebo gel to both breasts daily.

In both arms, treatment continues for 6-10 weeks before undergoing therapeutic surgical excision (TSE).

At baseline and the day before or the day of TSE, patients complete the BESS questionnaire for symptom assessment and blood and nipple aspirate samples are collected for further analysis.

After completion of study treatment, patients are followed up at 1 month.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of ductal carcinoma in situ (DCIS) of the breast with no evidence of invasion by core needle biopsy
- Grade 2 or 3 disease (Page and Lagois)
- No palpable DCIS
- Newly diagnosed disease
No mass lesion ≥ 5 mm on mammogram or ultrasound or an area of calcifications > 5 cm on mammogram
No DCIS of comedo subtype (i.e., solid DCIS, nuclear grade 3, and confluent necrosis)
Hormone receptor status: estrogen receptor (ER)-positive disease (> 5% cells staining for ER)

PATIENT CHARACTERISTICS:

Pre- and postmenopausal status
ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%
Leukocytes ≥ 3,000/mm^3
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Total bilirubin normal
AST/ALT ≤ 1.5 times upper limit of normal
Creatinine normal
Not pregnant or nursing within the past 3 months and for 3 months after completion of study treatment
Negative pregnancy test
Fertile patients must use effective contraception (barrier, abstinence, or non-hormonal intrauterine devices) during and for 3 months after completion of study treatment
Able and willing to schedule resection of DCIS lesion for 6-10 weeks after the start of study treatment
Willing to avoid exposing breast skin to natural or artificial sunlight (i.e., tanning beds) for the 6-10 weeks of study treatment
No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would limit compliance with study requirements
No history of or at high risk to develop thromboembolic disease
No dermatologic conditions resulting in skin breakdown in the area of gel application
No history of previous invasive or non-invasive breast cancer
No history of allergic reactions attributed to compounds of similar chemical or biological composition to 4-hydroxytamoxifen or tamoxifen citrate

PRIOR CONCURRENT THERAPY:

More than 2 years since prior tamoxifen citrate or other selective estrogen receptor modulators (SERM)
- Patients who have discontinued SERM therapy because of thromboembolic or uterine toxicity are not eligible
More than 30 days since prior exogenous sex hormones
More than 6 months since breast reduction or augmentation
No other concurrent investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00952731

Locations

United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Recruiting
Chicago, Illinois, United States, 60611-3013
Contact: Clinical Trials Office - Robert H. Lurie Comprehensive Cancer 312-695-1301 cancer@northwestern.edu
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Julie Margenthaler, MD 314-362-2280
United States, North Carolina
Duke University Medical Center	Recruiting
Durham, North Carolina, United States, 27704
Contact: Lee G. Wilke, MD 919-660-2244

Sponsors and Collaborators

Robert H. Lurie Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Raymond C. Bergan, MD

Robert H. Lurie Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Robert H. Lurie Comprehensive Cancer Center at Northwestern University ( Raymond C. Bergan )
Study ID Numbers:	CDR0000650556, NU-NWU07-9-02, NCI-07-9-02
Study First Received:	August 4, 2009
Last Updated:	December 23, 2009
ClinicalTrials.gov Identifier:	NCT00952731 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

ductal breast carcinoma in situ
estrogen receptor-positive breast cancer

Additional relevant MeSH terms:

4-hydroxytamoxifen
Antineoplastic Agents
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Neoplasms by Site
Carcinoma in Situ
Therapeutic Uses
Breast Diseases
Estrogen Antagonists
Neoplasms by Histologic Type

Skin Diseases
Antineoplastic Agents, Hormonal
Breast Neoplasms
Tamoxifen
Pharmacologic Actions
Carcinoma
Carcinoma, Ductal
Neoplasms
Carcinoma, Ductal, Breast
Carcinoma, Intraductal, Noninfiltrating
Neoplasms, Ductal, Lobular, and Medullary
Adenocarcinoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on February 04, 2010