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

NCT00952731 | Completed Phase 2 Results DMC

• 5 other identifiers: NWU07-9-02NCI-2013-00452NCI 07-9-02P30CA060553N01CN35157
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ductal Breast Carcinoma in Situ; Estrogen Receptor-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Difference Between Ki-67 Labeling Index in Tissue Samples Taken at Baseline and Post-treatment

  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).

  Baseline and after 4-10 weeks of treatment

Secondary Outcomes (5)

• Difference in Mean Score for Vasomotor Symptoms Including Hot Flashes From Baseline to Time of Surgery

  Baseline and after 4-10 weeks of treatment

• Difference in vWF Coagulation Protein in Blood Collected at Baseline and Just Prior to Surgery

  Baseline to immediately before surgery (after approximately 4-10 weeks)

• Difference in Factor VIII Coagulation Protein in Blood Collected at Baseline and Just Prior to Surgery

  Baseline and immediately before surgery (after approximately 4-10 weeks)

• Difference in Factor IX Coagulation Protein in Blood Collected at Baseline and Just Prior to Surgery

  Baseline and immediately before surgery (after approximately 4-10 weeks)

• Difference in Protein S Coagulation Protein in Blood Collected at Baseline and Just Prior to Surgery

  Baseline and immediately before surgery (after approximately 4-10 weeks)

Other Outcomes (5)

• Compare Concentrations of Tamoxifen and Its Metabolites (4-hydroxytamoxifen, Endoxifen, N-desmethyl Tamoxifen (NDT)) Obtained From Samples on the Day of Surgery

  Day of surgery (after approximately 4-10 weeks)

• Drug Metabolite Levels in the Two Study Groups by CYP2D6 Polymorphism Status

  28-70 days

• 4-OHT Affects Known Tamoxifen-modulated Pathways

  28-70 days

Study Arms (2)

oral placebo, afimoxifene

EXPERIMENTAL

4-hydroxytamoxifen gel 2mg/breast applied daily. Oral placebo taken daily.

Drug: oral placebo; Drug: afimoxifene

tamoxifen citrate, placebo gel)

ACTIVE COMPARATOR

Placebo gel applied to the breasts daily. 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules).

Drug: tamoxifen citrate; Drug: placebo gel

Interventions

oral placebo DRUG

Oral placebo taken daily for 4-10 weeks.

Also known as: PLCB

oral placebo, afimoxifene

afimoxifene DRUG

2mg/breast applied daily in the form of a gel for 4-10 weeks.

Also known as: 4-Hydroxy-Tamoxifen, 4-hydroxytamoxifen

oral placebo, afimoxifene

tamoxifen citrate DRUG

20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.

Also known as: Nolvadex, TAM, tamoxifen, TMX

tamoxifen citrate, placebo gel)

placebo gel DRUG

Placebo gel applied to breasts daily for 4-10 weeks.

Also known as: PLCB

tamoxifen citrate, placebo gel)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• ECOG performance status ≥1 (Karnofsky ≥70%)
• Participants must have normal organ and marrow function as defined below:
• Leukocytes≥3,000/uL
• Absolute neutrophil count (ANC)≥1,500/uL
• Platelets≥100,000/uL
• Total bilirubin within normal institutional limits
• AST (SGOT)/ALT (SGPT)≤1.5 X institutional ULN
• Creatinine within normal institutional limits
• 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.
• Ability to understand and the willingness to sign a written informed consent document.
• Ability and willingness to schedule surgical resection of DCIS lesion for 4-10 weeks (28-70 days) following the start of study agent.
• Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the 4-10 weeks of study agent dosing.

You may not qualify if:

• Prior history of, or at high risk to develop, thromboembolic disease will be excluded.
• Must not have taken exogenous sex hormones since biopsy diagnosing DCIS and must agree not to use exogenous sex hormones while on study.
• 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.
• May not be receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 4-hydroxytamoxifen or tamoxifen.
• 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.
• 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.
• 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.
• Must not have any dermatologic conditions resulting in skin breakdown in the area of gel application.
• Must not have a history of previous ipsilateral radiation to the affected breast.
• 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.

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating

Interventions

afimoxifene; Tamoxifen

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

The study was originally designed to enroll 112 participants, unfortunately, the shelf-life of the study drug expired which resulted in early closure of the study after only 31 participants.

Results Point of Contact

• Title: Dr. Seema Khan
• Organization: Northwestern University

s-khan2@northwestern.edu

312-503-4236

Study Officials

• Seema Khan

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 4, 2009
• First Posted: August 6, 2009
• Study Start: December 1, 2009
• Primary Completion: September 1, 2011
• Last Updated: July 21, 2015
• Results First Posted: July 21, 2015

Record last verified: 2015-07

Locations

US (1)