Testing an Active Form of Tamoxifen (4-hydroxytamoxifen) Delivered Through Breast Skin to Control Ductal Carcinoma in Situ (DCIS) of the Breast

NCT02993159 | Completed Phase 2 Results DMC FDA Drug

• 6 other identifiers: NCI 2015-06-04P30CA060553NCI-2016-01911N01-CN-2012-00035NWU2015-06-04N01CN00035
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 6

Brief Summary

This randomized phase IIB trial studies how well tamoxifen or afimoxifene works in treating patients with estrogen receptor positive breast cancer. Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen citrate or afimoxifene may fight breast cancer by blocking the use of estrogen by the tumor cells.

Conditions

Ductal Breast Carcinoma In Situ; Estrogen Receptor Positive

Outcome Measures

Primary Outcomes (1)

• Change in Ki-67 Labeling Index

  Change in the Ki-67 labelling index of DCIS lesions evaluated using immunohistochemistry

  baseline to up to 10 weeks

Secondary Outcomes (8)

• Change in Oncotype DCIS-Score

  baseline to up to 10 weeks

• Post-therapy Breast Tissue Levels of Tamoxifen and Its Metabolites

  up to 10 weeks

• Post-therapy Plasma Levels of Tamoxifen and Its Metabolites

  up to 10 weeks

• Ki-67 Labelling Index in the Terminal Duct Lobular Units (TDLUs)

  baseline to up to 10 weeks

• Change in Plasma Proteins Involved in Coagulation

  baseline to up to 10 weeks

Study Arms (2)

Arm I (afimoxifene, placebo)

EXPERIMENTAL

Patients apply afimoxifene gel to both breasts and receive placebo PO daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.

Drug: Afimoxifene; Other: Laboratory Biomarker Analysis; Other: Placebo

Arm II (placebo, tamoxifen citrate)

ACTIVE COMPARATOR

Patients apply placebo gel to both breasts and receive tamoxifen citrate orally PO daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.

Other: Laboratory Biomarker Analysis; Other: Placebo; Drug: Tamoxifen Citrate

Interventions

Afimoxifene DRUG

Applied to the breast

Also known as: 4-Hydroxy-Tamoxifen, 4-Hydroxytamoxifen, 4-OHT

Arm I (afimoxifene, placebo)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (afimoxifene, placebo); Arm II (placebo, tamoxifen citrate)

Placebo OTHER

Given PO

Also known as: placebo therapy, PLCB, sham therapy

Arm I (afimoxifene, placebo)

Tamoxifen Citrate DRUG

Given PO

Also known as: Apo-Tamox, Clonoxifen, Dignotamoxi, Ebefen, Emblon, Estroxyn, Fentamox, Gen-Tamoxifen, Genox, ICI 46,474, ICI-46474, Jenoxifen, Kessar, Ledertam, Lesporene, Nolgen, Noltam, Nolvadex, Nolvadex-D, Nourytam, Novo-Tamoxifen, Novofen, Noxitem, Oestrifen, Oncotam, PMS-Tamoxifen, Soltamox, TAM, Tamax, Tamaxin, Tamifen, Tamizam, Tamofen, Tamoxasta, Tamoxifeni Citras, Zemide

Arm II (placebo, tamoxifen citrate)

Eligibility Criteria

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

You may qualify if:

• Screen-detected, estrogen receptor (ER) positive DCIS of the breast proven on core needle biopsy, defined as 10% positive cells; the presence of a focus suspicious for microinvasion will be allowed; the size of the DCIS in the core biopsy sample must total 5 mm (multiple cores can be summed) and must be estimated on the deepest step section (if step sections are taken)
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Participants must have acceptable organ and marrow function as defined below:
• Baseline lab parameters are not standard of care for initiation of tamoxifen therapy; a minimal panel will therefore be appropriate.
• Leukocytes \>= 3,000/microliter
• Absolute neutrophil count \>= 1,500/microliter
• Platelets \>= 100,000/microliter
• Total bilirubin within "≤1.5 x institutional upper limit of normal (ULN)institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x institutional upper limit of normal (ULN)
• Creatinine within "≤1.5 x institutional upper limit of normal (ULN) institutional limits
• Women of childbearing potential and their male partners must agree to use TWO effective forms of birth control (abstinence is not an allowed method) prior to study entry and for the duration of study participation, and for two months following the last dose of study medications; effective birth control methods are: copper IUD \[intrauterine device\], diaphragm/cervical cap/shield, spermicide, contraceptive sponge, condoms; women of childbearing potential must have a negative urine pregnancy test within seven days before starting study medications; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of the study
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• DCIS presentation as a palpable mass
• Exogenous sex steroid use within 4 weeks prior to core needle biopsy
• Prior ipsilateral breast cancer radiotherapy will be excluded; prior contralateral breast cancer therapy within 2 years will also be excluded
• Skin lesions on the breast that disrupt the stratum corneum (eg eczema, ulceration)
• History of endometrial neoplasia
• History of thromboembolic disease (history of varicose veins and superficial phlebitis is allowed)
• Current smokers
• Current users of potent inhibitors of tamoxifen metabolism must be able to discontinue their use and switch to an alternative medication for the duration of participation, under the advice of their physician; if the physician feels that an alternative medication is not appropriate for the subject and the current medication is medically necessary, the subject will not be eligible; the drugs are listed below; many of these are not in clinical use at the moment; bupropion, celecoxib, chlorpheniramine, chlorpromazine, cimetidine, citalopram, clemastine, clomipramine, clozapine, cocaine, delavirdine, desipramine, diphenhydramine, doxepin, duloxetine, escitalopram, fluoxetine, haloperidol, halofantrine, hydroxyzine, imipramine, isoniazid, ketoconazole, methadone, methimazole, mibefradil, miconazole, nicardipine, paroxetine, pergolide, perphenazine, pioglitazone, pyrimethamine, quinidine, quinine, ranitidine, ritonavir, ropinirole, sertraline, terbinafine, thioridazine, ticlopidine, tranylcypromine, trazodone, tripelennamine
• Prior use of SERMS or AIs including tamoxifen, raloxifene, anastrozole, letrozole, or exemestane for prevention or therapy within 5 years
• Participants may not be receiving any other investigational agents within 30 days of enrollment or during this study
• History of allergic reactions attributed to tamoxifen or compounds of similar chemical or biologic composition
• 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; breastfeeding should be discontinued by nursing mothers who agree to participate in the study
• Men are excluded from this study since DCIS of the breast is exceedingly rare in men, and there are no data regarding skin penetration of 4-OHT though male chest wall skin (which is thicker and hairier than female chest wall skin)

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator
• BHR Pharma, LLC: collaborator

Study Sites (6)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Saint Elizabeth Medical Center South

Edgewood, Kentucky, 41017, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

• Khan SA, Mi X, Xu Y, Blanco LZ Jr, Akasha AM, Pilewskie M, Degnim AC, AlHilli Z, Amin AL, Hwang ES, Guenther JM, Kocherginsky M, Benante K, Zhang S, Helland T, Hustad SS, Gursel DB, Mellgren G, Dimond E, Perloff M, Heckman-Stoddard BM, Lee O. Presurgical Oral Tamoxifen vs Transdermal 4-Hydroxytamoxifen in Women With Ductal Carcinoma In Situ: A Randomized Clinical Trial. JAMA Surg. 2023 Dec 1;158(12):1265-1273. doi: 10.1001/jamasurg.2023.5113.

  PMID: 37870954 DERIVED

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating

Interventions

afimoxifene; 4,17 beta-dihydroxy-4-androstene-3-one; 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

Results Point of Contact

• Title: Seema A. Khan, MD
• Organization: Northwestern University

s-khan2@northwestern.edu

312-503-4236

Study Officials

• Seema Khan, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2016
• First Posted: December 15, 2016
• Study Start: May 31, 2017
• Primary Completion: March 30, 2021
• Study Completion: January 24, 2022
• Last Updated: December 18, 2024
• Results First Posted: December 18, 2024

Record last verified: 2024-09

Locations

US (6)