Ignite Creation Date:
2025-12-24 @ 2:48 PM
Ignite Modification Date:
2026-02-25 @ 7:06 PM
Study NCT ID:
NCT02993159
Status:
COMPLETED
Last Update Posted:
2024-12-18
First Post:
2016-12-14
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Testing an Active Form of Tamoxifen (4-hydroxytamoxifen) Delivered Through Breast Skin to Control Ductal Carcinoma in Situ (DCIS) of the Breast
Sponsor:
Northwestern University
Organization:
Study Overview
Official Title:
Phase IIB Pre-Surgical Trial of Oral Tamoxifen Versus Transdermal 4-hydroxytamoxifen in Women With DCIS of the Breast
Status:
COMPLETED
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 Description:
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 4-10 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.
VIII. To compare post-therapy changes in plasma markers of systemic estrogenic effect (IGF-1, SHBG).
IX. To compare post-therapy changes in symptoms as captured in the breast cancer prevention trial (BCPT) Eight Symptom Scale (BESS) questionnaire and skin reactions to 4-OHT gel.
OUTLINE: Patients are randomized into 1 of 2 arms.
ARM I: Patients apply afimoxifene gel to both breasts and receive placebo orally (PO) daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.
ARM II: 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.
After completion of study treatment, patients are followed up at 1-2 weeks and 1 month after surgery.
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 4-10 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.
VIII. To compare post-therapy changes in plasma markers of systemic estrogenic effect (IGF-1, SHBG).
IX. To compare post-therapy changes in symptoms as captured in the breast cancer prevention trial (BCPT) Eight Symptom Scale (BESS) questionnaire and skin reactions to 4-OHT gel.
OUTLINE: Patients are randomized into 1 of 2 arms.
ARM I: Patients apply afimoxifene gel to both breasts and receive placebo orally (PO) daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.
ARM II: 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.
After completion of study treatment, patients are followed up at 1-2 weeks and 1 month after surgery.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| P30CA060553 | NIH | None | https://reporter.nih.gov/quic… | View |
| NCI-2016-01911 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| N01-CN-2012-00035 | None | None | View | |
| NCI 2015-06-04 | OTHER | Northwestern University | View | |
| NWU2015-06-04 | OTHER | DCP | View | |
| N01CN00035 | NIH | None | https://reporter.nih.gov/quic… | View |