Alpha-TEA and Trastuzumab for the Treatment of Refractory HER2+ Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT04120246|
Recruitment Status : Recruiting
First Posted : October 9, 2019
Last Update Posted : November 30, 2020
|Condition or disease||Intervention/treatment||Phase|
|Anatomic Stage IV Breast Cancer AJCC v8 HER2 Positive Breast Carcinoma Metastatic Breast Carcinoma Prognostic Stage IV Breast Cancer AJCC v8 Refractory Breast Carcinoma||Drug: Alpha-tocopheryloxyacetic Acid Biological: Trastuzumab||Phase 1|
This is a dose-escalation study of alpha-TEA.
Patients receive one of 4 doses of alpha-TEA orally (PO) on days 1-14. Patients also receive trastuzumab on day 1 of cycle 1 and then every 3 weeks per standard of care. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 4 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Dose Escalation Trial of Alpha-Tocopheryloxyacetic Acid (α-TEA) in Patients With Treatment Refractory HER2+ Metastatic Breast Cancer|
|Actual Study Start Date :||April 8, 2020|
|Estimated Primary Completion Date :||February 1, 2022|
|Estimated Study Completion Date :||February 1, 2022|
Experimental: Treatment (alpha-TEA, trastuzumab)
Patients receive one of 4 doses of alpha-TEA PO on days 1-14. Patients also receive trastuzumab on day 1 of cycle 1 and then every 3 weeks per standard of care. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Alpha-tocopheryloxyacetic Acid
- Incidence of adverse events of 4 escalating doses of alpha-tocopheryloxyacetic acid (TEA) therapy when combined with trastuzumab [ Time Frame: Up to 4 years ]Toxicity grading will be evaluated per Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
- Clinical response rate of alpha-TEA when combined with trastuzumab [ Time Frame: Up to 4 years ]Clinical response will be performed by computed tomography (CT) scan of the chest, abdomen, and pelvis performed prior to enrollment and then after every 3 cycles per standard of care. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and immune related (ir)RECIST criteria will be used to determine response. Both progression free survival (PFS) and overall survival (OS) will be measured.
- Change in level of activated effector memory CD4+ and CD8+ T-cells at 4 escalating doses of alpha-TEA and concurrent trastuzumab [ Time Frame: At baseline, at cycle 4 Day 1, and then Day 1 of every 4th cycle while on study (each cycle is 28 days), assessed up to 4 years ]The level of memory CD4+ and CD8+ T cells will be evaluated by flow cytometry. Memory CD4+ T cells will be defined as CD3+CD4+CD38+HLA-DR+CCR7-CD45RA- and memory CD8+ T cells will be defined as CD3+CD8+CD38+ HLA-DR+CCR7-CD45RA-.
- Change in the number of HER2 specific T cells at each dose level [ Time Frame: Baseline up to 4 years ]Will determine if concurrent alpha-TEA and trastuzumab increase the number of HER2 specific T cells at each dose level. Endogenous immunity to HER2 will be evaluated using interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) assay. A statistically significant increase of HER2 specific immunity after concurrent alpha-TEA and trastuzumab treatment when compared to baseline will constitute augmentation of HER2 specific immunity.
- Modulation of circulating natural killer (NK) cells with concurrent alpha-TEA and trastuzumab therapy [ Time Frame: At baseline, at cycle 4 Day 1, and then Day 1 of every 4th cycle while on study (each cycle is 28 days), assessed up to 4 years ]Flow cytometry will be used to assess the number of NK cells as defined by CD3-CD16+CD56+ cells from whole blood. Flow will be used to analyze the function of NK cells, specifically through degranulation markers (CD107a+) and through IFN-gamma production. The level of NK cell CD107+ uptake and IFN-gamma production in response to major histocompatibility complex (MHC) class 1 negative cell will be evaluated.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04120246
|Contact: William Gwinfirstname.lastname@example.org|
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: William Gwin 206-221-5956 email@example.com|
|Principal Investigator: William Gwin|
|Principal Investigator:||William Gwin||Fred Hutch/University of Washington Cancer Consortium|