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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Seema Khan, Northwestern University
ClinicalTrials.gov Identifier:
NCT00952731
First received: August 4, 2009
Last updated: July 18, 2015
Last verified: July 2015
  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. 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.


Condition Intervention Phase
Ductal Breast Carcinoma in Situ
Estrogen Receptor-positive Breast Cancer
Drug: oral placebo
Drug: afimoxifene
Drug: tamoxifen citrate
Drug: placebo gel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Pre-surgical Phase IIb Trial of Transdermal 4-Hydroxytamoxifen vs. Oral Tamoxifen in Women With Ductal Carcinoma in Situ of the Breast

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Difference Between Ki-67 Labeling Index in Tissue Samples Taken at Baseline and Post-treatment [ Time Frame: Baseline and after 4-10 weeks of treatment ] [ Designated as safety issue: No ]
    Ki-67 was measured in matched core and excision tissue samples containing DCIS (Ductal Carcinoma In-Situ) lesions, the core sample was at baseline while the excision sample was at surgery (after approximately 4-10 weeks of treatment).


Secondary Outcome Measures:
  • Difference in Mean Score for Vasomotor Symptoms Including Hot Flashes From Baseline to Time of Surgery [ Time Frame: Baseline and after 4-10 weeks of treatment ] [ Designated as safety issue: No ]
    Hot flashes were assessed by the Breast Cancer Prevention Trial Eight Symptom Scale (BESS) questionnaire. This questionnaire measures the incidence of a number of symptoms by asking participants how frequently they experienced them on a scale of 0-4 (0 being Not at All and 4 being Extremely often). BESS questionnaire was administered at baseline and time of surgery. The incidence of vasomotor symptoms (including hot flashes, night sweats, and cold sweats) was measured at baseline (Day 0) and end of treatment prior to surgery (at least 4 weeks later or up to 10 weeks, depending on scheduled surgery date), and changes in the mean score for hot flashes were observed.

  • Difference in vWF Coagulation Protein in Blood Collected at Baseline and Just Prior to Surgery [ Time Frame: Baseline to immediately before surgery (after approximately 4-10 weeks) ] [ Designated as safety issue: Yes ]
    The difference between vWF coagulation protein in blood samples collected at baseline and before surgery were measured using the immune-turbidimetric assay.

  • Difference in Factor VIII Coagulation Protein in Blood Collected at Baseline and Just Prior to Surgery [ Time Frame: Baseline and immediately before surgery (after approximately 4-10 weeks) ] [ Designated as safety issue: Yes ]
    The difference between Factor VIII coagulation protein in blood samples collected at baseline and before surgery was measured with VisuLize antigen ELISA Kits.

  • Difference in Factor IX Coagulation Protein in Blood Collected at Baseline and Just Prior to Surgery [ Time Frame: Baseline and immediately before surgery (after approximately 4-10 weeks) ] [ Designated as safety issue: Yes ]
    The difference between Factor IX coagulation protein in blood samples collected at baseline and before surgery was measured with VisuLize antigen ELISA Kits.

  • Difference in Protein S Coagulation Protein in Blood Collected at Baseline and Just Prior to Surgery [ Time Frame: Baseline and immediately before surgery (after approximately 4-10 weeks) ] [ Designated as safety issue: Yes ]
    The difference between protein S coagulation protein in blood samples collected at baseline and before surgery was measured using an ELISA Kit.


Other Outcome Measures:
  • Compare Concentrations of Tamoxifen and Its Metabolites (4-hydroxytamoxifen, Endoxifen, N-desmethyl Tamoxifen (NDT)) Obtained From Samples on the Day of Surgery [ Time Frame: Day of surgery (after approximately 4-10 weeks) ] [ Designated as safety issue: No ]
    Concentrations of tamoxifen and its metabolites: 4-hydroxytamoxifen, endoxifen, and NDT were measured in breast tissue, blood, and Nipple Aspirate Fluid (NAF) that was collected on the day of surgery.

  • Drug Metabolite Levels in the Two Study Groups by CYP2D6 Polymorphism Status [ Time Frame: 28-70 days ] [ Designated as safety issue: No ]
    Descriptive statistics and confidence intervals will be provided.

  • 4-OHT Affects Known Tamoxifen-modulated Pathways [ Time Frame: 28-70 days ] [ Designated as safety issue: No ]
    Descriptive statistics and confidence intervals will be provided.

  • TAM Metabolite Concentrations and Estrogen Response Markers in Nipple Aspiration Fluid (NAF) [ Time Frame: 28-70 days ] [ Designated as safety issue: No ]
    Descriptive statistics and confidence intervals will be provided.

  • E and Z 4-OHT Isomers [ Time Frame: 28-70 days ] [ Designated as safety issue: No ]
    Descriptive statistics and confidence intervals will be provided.


Enrollment: 27
Study Start Date: December 2009
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: oral placebo, afimoxifene
4-hydroxytamoxifen gel 2mg/breast applied daily. Oral placebo taken daily.
Drug: oral placebo
Oral placebo taken daily for 4-10 weeks.
Other Name: PLCB
Drug: afimoxifene
2mg/breast applied daily in the form of a gel for 4-10 weeks.
Other Names:
  • 4-Hydroxy-Tamoxifen
  • 4-hydroxytamoxifen
Active Comparator: tamoxifen citrate, placebo gel)
Placebo gel applied to the breasts daily. 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules).
Drug: tamoxifen citrate
20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.
Other Names:
  • Nolvadex
  • TAM
  • tamoxifen
  • TMX
Drug: placebo gel
Placebo gel applied to breasts daily for 4-10 weeks.
Other Name: PLCB

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. Diagnosis of hormone receptor positive (more than 5% cells staining for ER + and/ or PR +), any grade (using definition of Page and Lagios) ductal carcinoma in situ (DCIS) with or without evidence of microinvasion on diagnostic core needle biopsy within the previous 60 days.
  2. Women of age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of 4-hydroxytamoxifen in participants <18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable.
  3. ECOG performance status ≥1 (Karnofsky ≥70%)
  4. Participants must have normal organ and marrow function as defined below:

    1. Leukocytes≥3,000/uL
    2. Absolute neutrophil count (ANC)≥1,500/uL
    3. Platelets≥100,000/uL
    4. Total bilirubin within normal institutional limits
    5. AST (SGOT)/ALT (SGPT)≤1.5 X institutional ULN
    6. Creatinine within normal institutional limits
  5. Women of child-bearing potential must agree to practice barrier birth control, abstinence, or use non-hormonal IUDs from the time that the first pregnancy test is performed throughout the duration of the study and for three months after cessation of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
  6. Ability to understand and the willingness to sign a written informed consent document.
  7. Ability and willingness to schedule surgical resection of DCIS lesion for 4-10 weeks (28-70 days) following the start of study agent.
  8. Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the 4-10 weeks of study agent dosing.

Exclusion Criteria:

  1. Prior history of, or at high risk to develop, thromboembolic disease will be excluded.
  2. Must not have taken exogenous sex hormones since biopsy diagnosing DCIS and must agree not to use exogenous sex hormones while on study.
  3. Must not have taken tamoxifen or other selective estrogen receptor modulators (SERMs) within 2 years prior to entering the study. Women who have discontinued SERM therapy because of thromboembolic or uterine toxicity, will be excluded regardless of duration of use.
  4. May not be receiving any other investigational agents.
  5. History of allergic reactions attributed to compounds of similar chemical or biologic composition to 4-hydroxytamoxifen or tamoxifen.
  6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  7. Pregnant women are excluded from this study because tamoxifen and 4-hydroxytamoxifen has the potential for teratogenic or abortifacient effects. Women are excluded from enrolling within 3 months of the most recent pregnancy. Women must avoid becoming pregnant in the 3 months following the use of study agent.
  8. Women must not have breastfed within three months prior to DCNB. Women who are breast feeding are excluded from entry into this trial because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with tamoxifen or 4-hydroxytamoxifen. Women must agree to forego breastfeeding for three months following the use of study agent.
  9. Must not have any dermatologic conditions resulting in skin breakdown in the area of gel application.
  10. Must not have a history of previous ipsilateral radiation to the affected breast.
  11. Must not have had a breast reduction or augmentation within the 6 months prior to first dose of study agents. Patients who have had breast implants more than 6 months prior to first dose of study agents will be eligible.
  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: NCT00952731

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Seema Khan Northwestern University
  More Information

No publications provided

Responsible Party: Seema Khan, Professor, Northwestern University
ClinicalTrials.gov Identifier: NCT00952731     History of Changes
Other Study ID Numbers: NWU07-9-02, NCI-2013-00452, NCI 07-9-02, NCI-2013-00452, P30CA060553, N01CN35157
Study First Received: August 4, 2009
Results First Received: May 27, 2015
Last Updated: July 18, 2015
Health Authority: United States: Food and Drug Administration
United States: Data and Safety Monitoring Board
United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Carcinoma in Situ
Carcinoma, Ductal, Breast
Carcinoma, Intraductal, Noninfiltrating
Adenocarcinoma
Breast Diseases
Carcinoma, Ductal
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Ductal, Lobular, and Medullary
Neoplasms, Glandular and Epithelial
Skin Diseases
Afimoxifene
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 July 28, 2015