Title
Phase IB/II Clinical Trial of Alpelisib and Tucatinib in Patients With PIK3CA -Mutant HER2-Positive Metastatic Breast Cancer

Description
This study is a multicenter, single arm, open-label, run-in phase Ib safety cohort with immediate roll over to a phase II clinical trial that will test the combination therapy of tucatinib with alpelisib in subjects with PIK3CA-mutant HER2+ locally advanced unresectable or metastatic breast cancer. Patients with PIK3CA-mutant HR-/HER2+ and HR+/HER2+ breast cancer may enroll, the latter cohort will receive concomitant treatment with standard doses of fulvestrant to block HR signaling. In phase Ib part, we will confirm the tolerability of tucatinib and alpelisib combination and determine the maximum tolerated dose (MTD). In phase II part, we will expand the testing of this drug combination at MTD to determine the PFS rate.

Objective
Phase Ib
Primary
- Safety and tolerability of alpelisib and tucatinib combination
Secondary
- Pharmacokinetic (PK) properties of alpelisib and tucatinib
- Preliminary efficacy of alpelisib and tucatinib combination

Phase II
Primary objective
- Efficacy of tucatinib combination evaluated by progression free survival (PFS)
Secondary objectives
- Efficacy of tucatinib in combination with alpelisib evaluated by ORR, CBR and DOR
- Safety and tolerability of the combination therapy

Treatment Drug: Alpelisib
Drug: Tucatinib
Drug: Fulvestrant

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Breast

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital