Oral Tamoxifen vs. TamGel vs. Control in Women With Atypical Hyperplasia or Lobular Carcinoma In Situ

Sponsor

Amy C. Degnim (Other)

Overall Status

Recruiting

CT.gov ID

NCT04570956

Collaborator

(none)

104

Enrollment

Location

Arms

65.2

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators plan to prospectively study breast tissue changes after a short course of Tamoxifen (Tam).

Condition or Disease	Intervention/Treatment	Phase
Atypical Hyperplasia Lobular Carcinoma in Situ	Drug: Tamoxifen Drug: Topical 4-OHT( 4-hydroxytamoxifen)gel 2 mg/each breast/day Drug: Placebo	Phase 2/Phase 3

Detailed Description

Women with atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) are at increased risk of breast cancer (BC) (~1-2 % per year). Over two decades ago, placebo-controlled randomized trials established that oral tamoxifen (20 mg/day) reduces breast cancer risk by 50% in generally defined high risk women, with ~70% reduction in women at high risk specifically due to atypical hyperplasia.[1] Years later, the side effects and toxicity of oral tamoxifen at 20 mg/day remain a significant barrier to its uptake and longterm compliance.[2, 3] To address the issue of toxicity, two main strategies have been pursued: 1) using a lower dose of oral tamoxifen, and 2) using a topical formulation of tamoxifen to avoid systemic side effects. The investigators will perform a prospective study of women with AH or LCIS who will take a short course of prevention therapy; breast tissue samples will be evaluated pre- and post-therapy to identify and evaluate very early biomarkers of response. The overall goal of the study is to evaluate short-term changes in background breast tissue induced by either low-dose oral tamoxifen or topical 4-OHT gel in women with AH or LCIS.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

104 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Subjects will be randomized 2:2:1 with either Oral Tamoxifen 10 mg/day gel placebo, Topical 4-OHT gel 2 mg/each breast/day oral placebo, or Control Oral and gel placebo for 4 weeks of treatment.Subjects will be randomized 2:2:1 with either Oral Tamoxifen 10 mg/day gel placebo, Topical 4-OHT gel 2 mg/each breast/day oral placebo, or Control Oral and gel placebo for 4 weeks of treatment.

Masking:

Double (Care Provider, Investigator)

Masking Description:

Subjects with be randomized by MedidataRave and Pharmacy.

Primary Purpose:

Treatment

Official Title:

A Phase IIB Randomized Trial of Oral Tamoxifen vs. Topical 4-hydroxytamoxifen Gel vs. Control in Women With Atypical Hyperplasia or Lobular Carcinoma In Situ

Actual Study Start Date :

Jul 26, 2021

Anticipated Primary Completion Date :

Dec 31, 2026

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral Tamoxifen 10 mg/day Oral Tamoxifen 10 mg/day	Drug: Tamoxifen Oral Tamoxifen 10 mg/day Other Names: Oral tamoxifen
Experimental: Topical 4-OHT (4-hydroxytamoxifen) gel 2 mg/each breast/day Topical 4-OHT (4-hydroxytamoxifen) gel 2 mg/each breast/day +oral placebo	Drug: Topical 4-OHT( 4-hydroxytamoxifen)gel 2 mg/each breast/day Topical 4-OHT (4-hydroxytamoxifen) gel 2 mg/each breast/day Other Names: Topical gel
Experimental: Control Oral and gel placebo	Drug: Placebo placebo pill or placebo gel Other Names: placebo pill placebo gel

Arm

Intervention/Treatment

Experimental: Oral Tamoxifen 10 mg/day

Oral Tamoxifen 10 mg/day

Drug: Tamoxifen

Oral Tamoxifen 10 mg/day

Other Names:

Oral tamoxifen

Experimental: Topical 4-OHT (4-hydroxytamoxifen) gel 2 mg/each breast/day

Topical 4-OHT (4-hydroxytamoxifen) gel 2 mg/each breast/day +oral placebo

Drug: Topical 4-OHT( 4-hydroxytamoxifen)gel 2 mg/each breast/day

Topical 4-OHT (4-hydroxytamoxifen) gel 2 mg/each breast/day

Other Names:

Topical gel

Experimental: Control

Oral and gel placebo

Drug: Placebo

placebo pill or placebo gel

Other Names:

placebo pill

placebo gel

Outcome Measures

Primary Outcome Measures

The purpose of this research is to evaluate short-term changes in background breast tissue induced by oral tamoxifen or 4-OHT gel in women with atypical hyperplasia or lobular carcinoma in situ (LCIS). [48 months]
Treatment Evaluation/Measurement of Effect

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Willing to return to enrolling institution for follow-up
Willing to complete required testing
Ability to complete questionnaire by themselves or with assistance
Female (sex that was assigned at birth)
Ipsilateral intact breast with histology confirmation of atypical ductal or lobular hyperplasia, or LCIS, within the last 12 months, whether surgically excised or not.
Eastern Cooperative Oncology Group (ECOG) performance status ≤1
Willingness to agree to use ONE effective form of birth control (abstinence is not an allowed method) prior to study entry and for the duration of study participation, and for 2 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 pregnancy test within five days before starting study medications. Should a participant become pregnant or suspect she is pregnant while participating in this study; the participant should inform the study physician immediately.
Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of the study.
Participants must have acceptable organ and marrow function as defined below within 30 days of randomization: judged by treating physician's evaluation of baseline laboratory data.
Negative urine pregnancy test, if of childbearing potential. and / or FSH to verify menopausal status.

Exclusion Criteria:

Clinically suspicious mass/lesions Breast cancer in the past 5 years.
Prior thromboembolism within last 5 years (history of varicose veins and superficial phlebitis is allowed) Current pregnancy or lactation History of other prior breast cancer-specific therapy within the previous 2 years (chemotherapy, anti-HER2 agents, endocrine agents, everolimus, CDK4-6 inhibitors).
Cytotoxic chemotherapy for any indication in last 2 years.
Prior use of SERMS or AIs including tamoxifen, raloxifene, anastrozole, letrozole, or exemestane for prevention or therapy within 5 years.
Exogenous sex steroid, including oral contraceptive pill use within 1 month prior to research core needle biopsy (CNB).
Use of vaginally administered estrogens and hormone coated IUD such as Mirena is permitted History of any prior ipsilateral breast radiotherapy. Previous unilateral radiation of the contralateral side is allowed.
Skin lesions on the breast that disrupt the stratum corneum (eg eczema, ulceration).
History of endometrial neoplasia
Current smoker. Cessation for at least 6 weeks
Current users of potent inhibitors of tamoxifen metabolism. The potent inhibitors of tamoxifen metabolism are: bupropion, cinacalcet, fluoxetine, paroxetine, quinidine.
Participants may not be receiving any other investigational agents within 90 days of enrollment or during this study.
History of allergic reactions to tamoxifen.
Uncontrolled intercurrent illness that in the judgement of the treating physician would make them unsuitable for study participation
Anticoagulation meds and clinical concern for discontinuing meds for study research biopsy.
Identification of a clinically suspicious mass on examination.