Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion
Principal Investigator
by Saeed Sadeghi (ucla)

Description

Summary

This is a Phase II, multicenter, randomized, open-label, active-controlled trial designed to assess the safety and efficacy of the combination of dapagliflozin plus metformin extended release (XR) compared with metformin XR during treatment with alpelisib plus fulvestrant in participants with HR-positive, HER2-negative advanced breast cancer with a PIK3CA mutation following progression on or after endocrine-based therapy.

Official Title

EPIK-B4: A Phase II, Multicenter, Randomized, Open-label, Active-controlled Study to Assess the Safety and Efficacy of Dapagliflozin + Metformin XR Versus Metformin XR During Treatment With Alpelisib (BYL719) in Combination With Fulvestrant in Participants With HR+, HER2-, Advanced Breast Cancer With a PIK3CA Mutation Following Progression on/After Endocrine-based Therapy

Details

The study will only include participants who have at least one baseline risk factor for the development of severe hyperglycemia, defined as: - Diabetes (FPG ≥ 126 mg/dL or ≥ 7.0 mmol/L and/or HbA1c ≥ 6.5%) - Pre-diabetes (FPG ≥ 100 mg/dL to < 126 mg/dL or 5.6 to < 7.0 mmol/L and/or HbA1c 5.7 to < 6.5%) - Obesity (BMI ≥ 30) - Age ≥ 75 years Participants will be randomized in a 1:1 ratio (approximately 66 participants in each treatment arm) to receive the combination of dapagliflozin plus metformin XR or metformin XR alone starting on Cycle 1 Day 1. For both arms participants will receive fulvestrant starting at Cycle 1 Day 1 and alpelisib starting at Cycle 1 Day 8. Randomization will be stratified by diabetic status at baseline, i.e. normal vs pre- diabetic/diabetic (based on fasting plasma glucose (FPG) and/or hemoglobin A1c (HbA1c) laboratory values). The study will consist of a 28-day screening phase, a 12 cycle treatment phase, and a post-treatment phase which includes safety and efficacy follow-up (if applicable).

Keywords

Breast Cancer, Alpelisib, Fulvestrant, Metformin XR, Dapagliflozin + metformin XR, Advanced breast cancer, Phase II, HR+, HER2-, PIK3CA, Hyperglycemia, Breast Neoplasms, Metformin, Dapagliflozin, Alpelisib + Fulvestrant + Dapagliflozin + Metformin XR, Alpelisib + Fulvestrant + Metformin XR

Eligibility

You can join if…

Open to people ages 18 years and up

  • Participant has a histologically and/or cytologically confirmed diagnosis of estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) breast cancer by local laboratory
  • Participant has a PIK3CA mutation(s) present in tumor prior to enrollment
  • Participant has prior treatment with an endocrine-based treatment (i.e. letrozole, anastrozole, exemestane, fulvestrant or oral SERD) and may be:
  • relapsed with documented evidence of progression while on (neo) adjuvant endocrine- based therapy or within 12 months from completion of (neo)adjuvant endocrine-based therapy with no treatment for metastatic disease
  • relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine-based therapy and then subsequently progressed with documented evidence of progression while on or after only one line of endocrine-based therapy for metastatic disease
  • newly diagnosed advanced breast cancer, then relapsed with documented evidence of progression while on or after only one line of endocrine-based therapy.

Note: Participants with newly diagnosed endocrine-based treatment naïve advanced breast cancer will NOT be included in the study.

  • Participants may or may not have received prior CDK4/6i therapy. If prior CDK4/6i therapy was administered, it may have been in the adjuvant or metastatic setting
  • If female, then the participant is postmenopausal
  • Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Participant has adequate bone marrow and organ function

You CAN'T join if...

  • Participant who relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease
  • Participant had more than 1 line of prior treatment in the metastatic setting
  • Participant has received prior treatment with chemotherapy (except for neoadjuvant/adjuvant chemotherapy), any PI3K, Mammalian Target of Rapamycin (mTOR) or Protein Kinase B (Akt) inhibitor
  • Participant has inflammatory breast cancer at screening
  • Participants with an established diagnosis of diabetes mellitus type I or participants with type II diabetes mellitus requiring antihyperglycemic therapy
  • Participant has a history of acute pancreatitis within 1 year of screening or a past medical history of chronic pancreatitis
  • Participant has currently documented pneumonitis/interstitial lung disease
  • Participant has a history of severe cutaneous reaction, such as Steven-Johnson Syndrome (SJS), erythema multiforme (EM), Toxic Epidermal Necrolysis (TEN) or Drug Reaction with Eosinophilia and Systemic Syndrome (DRESS)

Other inclusion/exclusion criteria may apply

Locations

  • UCLA Medical Center accepting new patients
    Los Angeles California 90095 United States
  • Kaiser Permanente Medical Group Kaiser Hawaii - accepting new patients
    Anaheim California 92807 United States

Lead Scientist at UC Cancer

  • Saeed Sadeghi (ucla)
    HS Clinical Professor, Medicine. Authored (or co-authored) 9 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Novartis Pharmaceuticals
ID
NCT04899349
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 132 study participants
Last Updated