Clinical Trial: Tamoxifen Citrate or Afimoxifene in Treating Patients With Estrogen Receptor Positive Breast Cancer

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Phase IIB Trial of Neoadjuvant Oral Tamoxifen Versus Transdermal 4-hydroxytamoxifen in Women With DCIS of the Breast

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.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To demonstrate that 2 mg once daily per breast of 4-hydroxytamoxifen (4-OHT) topical gel results in a reduction in the Ki-67 labeling index of ductal breast carcinoma in situ (DCIS) lesions that is not inferior to that seen with 20 mg daily oral tamoxifen citrate (TAM) for 26 +/- 2 weeks, when comparing the base-line diagnostic core biopsy to the therapeutic surgical excision sample.

SECONDARY OBJECTIVES:

I. To compare post-therapy changes in the oncotype DCIS-score between arms (this is a validated reverse transcriptase-polymerase chain reaction [RT-PCR] assay for Ki67, STK15, survivin, cyclin B1, MYBL2, PR, GSTM1).

II. To compare between-group post-therapy changes in immunohistochemistry (IHC) markers: CD-68 macrophage marker as a surrogate for response to therapy, p16 and COX-2.

III. To compare post-therapy changes in breast density, quantitative estimate, between arms.

IV. To compare post-therapy breast tissue and plasma levels of TAM and its metabolites (N-desmethyl tamoxifen [NDT], [E] and [Z] isomers of 4-hydroxytamoxifen [4-OHT], N-desmethyl-4-hydroxytamoxifen [endoxifen]).

V. To compare post-therapy breast tissue and plasma levels of estradiol and progesterone between arms (optional).

VI. To compare the post-therapy fraction of participants demonstrating "no residual DCIS".

VII. To compare post-therapy changes in plasma proteins involved in coagulation: factors VIII and IX, von Willebrand factor, total protein S between arms.

Sponsor: BHR Pharma, LLC

Current Primary Outcome: Ki67 labeling assessed by standard immunohistochemistry [ Time Frame: Up to 1 month after surgery ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Breast density [ Time Frame: Up to 1 month after surgery ]
    Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
  • CD68, p16, and COX2 assessed by IHC [ Time Frame: Up to 1 month after surgery ]
    Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
  • Estradiol and progesterone levels in breast tissue and plasma assessed by liquid chromatography/tandem mass spectrometry [ Time Frame: Up to 1 month after surgery ]
    Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
  • Fraction of subjects with "no residual DCIS" in surgical sample assessed by core needle biopsy [ Time Frame: Up to 1 month after surgery ]
    Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
  • Oncotype DCIS-score assessed by RT-PCR [ Time Frame: Up to 1 month after surgery ]
    Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
  • Pathologic complete response defined as absence of residual DCIS or residual DCIS responded completely to therapy [ Time Frame: Up to 1 month after surgery ]
  • Plasma markers of systemic estrogenic effect (IGF-1, SHBG) [ Time Frame: Up to 1 month after surgery ]
    Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
  • Plasma proteins involved in coagulation (factors VIII and IX, von Willebrand factor, and total protein S) [ Time Frame: Up to 1 month after surgery ]
    Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
  • Symptoms assessed by BESS questionnaire [ Time Frame: Up to 1 month after surgery ]
    Will evaluate hot flashes, vaginal discharge/dryness, skin reactions to afimoxifene gel. Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
  • TAM and its metabolites levels in breast tissue and plasma [ Time Frame: Up to 1 month after surgery ]
    Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.


Original Secondary Outcome: Same as current

Information By: National Cancer Institute (NCI)

Dates:
Date Received: December 14, 2016
Date Started: June 1, 2017
Date Completion: July 15, 2019
Last Updated: May 10, 2017
Last Verified: May 2017