Study of Safety and Efficacy of Dapagliflozin + Metformin XR Versus Metformin XR in Participants With HR+, HER2-, Advanced Breast Cancer While on Treatment With Alpelisib and Fulvestrant

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

ClinicalTrials.gov Identifier: NCT04899349

Novartis Reference Number: CBYL719C2202

Last Update: Nov 14, 2022

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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.

Condition 
Breast Cancer
Phase 
Phase 2
Overall status 
Recruiting
Start date 
Apr 06, 2022
Completion date 
Oct 13, 2029
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Alpelisib
Alpelisib (tablets) administered at 300mg orally once daily on a continuous dosing schedule starting on Cycle 1 Day 8 in a 28 days cycle.
Drug
Fulvestrant
Fulvestrant (prefilled syringe) 500mg administered intramuscularly at Cycle 1 Day 1 and 15 after randomization and then at Day 1 of each subsequent cycle during the randomized treatment phase.
Drug
Metformin XR
Metformin XR (tablets) administered at a starting dose of 500mg orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 days cycle. Dose titration from 500 mg once a day to 2000 mg once a day.
Drug
Dapagliflozin + metformin XR
Dapagliflozin + metformin XR administered as a single tablet combination at a starting dose of 5 mg dapagliflozin + 500 mg metformin XR orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 days cycle. Dose titration from 5 mg dapagliflozin + 500 mg metformin XR orally once daily to 10 mg dapagliflozin + 2000 mg metformin XR once daily
Drug
Dapagliflozin
Dapagliflozin (tablet) at a starting dose of 5mg orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 days cycle. Dose titration from 5 mg to 10 mg once daily

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Locations

United States
Alaska Oncology and Hematology AOH (2)
Recruiting
Anchorage, 99508 - Alaska
Contact: (907-264-1579) Steven Liu
United States
Highlands Oncology Group
Recruiting
Fayetteville, 72703 - Arkansas
Contact: Sophia Rudman (479-878-7098) - [email protected] - J. Thaddeus Beck
United States
Kaiser Permanente Medical Group Kaiser Hawaii -
Recruiting
Anaheim, 92807 - California
Contact: (808-432-8587) Jennifer Carney
United States
UCLA Medical Center
Recruiting
Los Angeles, 90095 - California
Contact: Amy Hidalgo - [email protected] - Saeed Sadeghi
United States
Rocky Mountain Cancer Centers RMCC Hale Pkwy
Recruiting
Longmont, 80501 - Colorado
Contact: Vanessa Anderson (303-321-0302) - [email protected] - Mabel Mardones
United States
Mayo Clinic Jacksonville
Recruiting
Jacksonville, 32224 - Florida
Contact: Megan Skoglund (904-953-2451) - [email protected] - Sarika Rao
United States
Georgia Cancer Specialists
Recruiting
Decatur, 30033 - Georgia
Contact: Greta Dudley (770-496-9400) - [email protected] - Gena Volas-Redd
United States
Mayo Clinic - Rochester Onc Dept
Recruiting
Rochester, 55905 - Minnesota
Contact: (507-284-2401) Karthik Giridhar
United States
Washington University School of Medicine Siteman Cancer Center
Recruiting
Saint Louis, 63110 - Missouri
Contact: Lizzy Ainsworth (314-747-8085) - [email protected] - Lindsay L Peterson
United States
St Vincent Frontier Cancer Center
Recruiting
Billings, 59102 - Montana
Contact: Amanda Klein (406-238-6962) - [email protected] - Patrick Cobb
United States
Astera Cancer Center
Recruiting
East Brunswick, 08816 - New Jersey
Contact: Stephanie Marks (732-390-7750) - [email protected] - Bruno Fang
United States
Duke Cancer Institute
Recruiting
Durham, 27710 - North Carolina
Contact: Marsha Mcmurtry (919-660-1278) - [email protected] - Heather Moore
United States
Texas Oncology Austin
Recruiting
Austin, 78731 - Texas
Contact: (512-427-9400) Debra A Patt
United States
Texas Oncology PA Dallas Presbyterian Hospital SC
Recruiting
Dallas, 75231 - Texas
Contact: Rosita Lopez (214-265-2080) - [email protected] - Kristi J McIntyre
United States
Tx Onco Sammons Cancer Center
Recruiting
Dallas, 75246 - Texas
Contact: Julie Morehouse (214-370-1000) - [email protected] - Joyce A O Shaughnessy
United States
Texas Oncology Denton
Recruiting
Denton, 76201 - Texas
Contact: Alex Bernard (940-382-1022) - [email protected] - Charles Kurkul
United States
Texas Oncology PA - Tyler
Recruiting
Tyler, 75702 - Texas
Contact: Shelly Maxfield (903-579-9800) - [email protected] - Sasha Strain
United States
Virginia Oncology Associates VOA - Lake Wright
Recruiting
Norfolk, 23502 - Virginia
Contact: Kara Wiggins (757-213-5637) - [email protected] - Michael A. Danso
United States
Northwest Medical Specialties NW Medical Specialties
Recruiting
Tacoma, 98405 - Washington
Contact: Patricia Walsh (253-841-4296) - [email protected] - Sibel Blau
United States
Hong Kong
Novartis Investigative Site
Recruiting
Hong Kong, 999077
-
Hong Kong
Novartis Investigative Site
Recruiting
Hong Kong,
-
Hong Kong
Malaysia
Novartis Investigative Site
Recruiting
Kuala Lumpur, 50586
Wilayah Persekutuan
Malaysia
Novartis Investigative Site
Recruiting
Putrajaya, 62250
Wilayah Persekutuan
Malaysia
Novartis Investigative Site
Recruiting
Kuala Lumpur, 59100
-
Malaysia
Novartis Investigative Site
Recruiting
Pulau Pinang, 10990
-
Malaysia
Philippines
Novartis Investigative Site
Recruiting
Quezon City, 1102
-
Philippines
Novartis Investigative Site
Recruiting
San Juan City, 1500
-
Philippines
Saudi Arabia
Novartis Investigative Site
Recruiting
Riyadh, 7805
-
Saudi Arabia
Singapore
Novartis Investigative Site
Recruiting
Singapore, 119228
-
Singapore

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 

Have a question?

Call 1-888-669-6682 or email [email protected]