Study to Evaluate Biomarkers and Safety of Dapagliflozin Concomitant With Neoadjuvant Therapy
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexFemale
Age18+
SponsorYale University
About this trial
The primary objective of the study is to assess metabolic plasma markers of insulin resistance in patients with early-stage HER2-negative breast cancers receiving dapagliflozin concomitant with neoadjuvant therapy.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Weekly or dose dense paclitaxel, followed by dose dense doxorubicin plus cyclophosphamide
Docetaxel plus cyclophosphamide
Docetaxel plus carboplatin plus or minus pembrolizumab
Paclitaxel plus carboplatin concurrent with every 3 week pembrolizumab followed by dose dense doxorubicin plus cyclophosphamide concurrent with every 3 week pembrolizumab (KEYNOTE-522 regimen; only for participants with triple negative breast cancer)
Disqualifiers
Participants who underwent partial excisional biopsy or lumpectomy, segmental mastectomy or modified radical mastectomy or sentinel node biopsy and therefore cannot be assessed accurately for pathologic response, are not eligible.
Participants currently pregnant or breastfeeding.
Participants for whom any of the planned chemotherapies are contraindicated.
Participants with currently diagnosed type I or II diabetes mellitus.
Trial design
Design model
Single group
Treatments tested in this trial
Dapagliflozin 10mg
Drug10 mg tablets for oral administration daily throughout chemotherapy treatment
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: DapagliflozinExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Change in Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)
Change in HOMA-IR (calculated as fasting insulin (μU/ml) x fasting glucose (mmol/l) divided by 22.5.
Time frame
baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapySecondary outcomes
1
Change in Fasting glucose concentration
Fasting plasma glucose concentration will be assessed following an overnight fast at baseline and 12 weeks post treatment
Time frame
baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy2
Change in Fasting insulin concentration
Fasting plasma insulin concentration will be assessed at baseline and 12 weeks post treatment
Time frame
baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy3
Total and phosphorylated PKB/AKT
Immunohistochemistry (IHC) staining for expression of Total and phosphorylated PKB/AKT in breast cancer tissue, before and after (in participants with residual cancer) treatment. For quantification of IHC, sections will be scored manually by a pathologist using the Allred system, a clinical instrument based on the percentage of cells that stain by immunohistochemistry for PKB/AKT (on a scale of 0 to 5) and the intensity of that staining (on a scale of 0 to 3, for a possible maximum total score of 8. The lower the number the less staining.
Time frame
baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapy4
Total and phosphorylated insulin receptor
Immunohistochemistry (IHC) staining for expression of Total and phosphorylated insulin receptor in breast cancer tissue, before and after (in participants with residual cancer) treatment. For quantification of IHC, sections will be scored manually by a pathologist using the Allred system, a clinical instrument based on the percentage of cells that stain by immunohistochemistry for PKB/AKT (on a scale of 0 to 5) and the intensity of that staining (on a scale of 0 to 3, for a possible maximum total score of 8. The lower the number the less staining.
Time frame
baseline, post paclitaxel treatment at week 12, and 2 weeks post neoadjuvant therapySponsors and contacts
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Source ClinicalTrials.gov