NCT04526470

Alpelisib and Paclitaxel in PIK3CA-altered Gastric Cancer

Phase IB/II Study of Alpelisib in Combination With Paclitaxel in Patients With PIK3CA-altered Metastatic/Recurrent Gastric Cancer

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Sponsor: Seoul National University Bundang Hospital · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

Alpelisib (BYL719) is a PIK3CA-specific inhibitor, which was developed by Novartis (Basel, Switzerland). Our group conducted pre-clinical study of alpelisib in eight gastric cancer cell lines: four PIK3CA wild-type (SNU638, SNU668, SNU1, and SNU16) and four PIK3CA mutant (SNU719, AGS, SNU601, and MKN). As a result, alpelisib preferentially inhibited the growth of gastric cancer cells with PIK3CA mutations. In addition, alpelisib inhibited cell growth via G1 arrest and subsequently induces apoptosis in GC cells, and this effect is more remarkable in cells harboring PIK3CA mutations. Moreover, alpelisib in combination with paclitaxel showed synergistic cytotoxic effects and significantly increased apoptosis compared with alpelisib or paclitaxel monotherapy in GC cells. The purpose of the study is to define the maximal tolerated dose (MTD) and recommended phase II dose (RP2D) of paclitaxel and alpelisib combination therapy in patients with advanced tumors and to evaluate the efficacy of paclitaxel and AZD8186 combination therapy as a second-line therapy in patients with advanced gastric cancer with PTEN aberrations. This study is divided into Phase IB and Phase II.

Conditions

• Solid Tumor
• Stomach Cancer

Interventions

Type	Name	Description
DRUG	Alpelisib	Dose level -2: 200 mg PO once daily / Dose level -1: 200 mg PO once daily / Dose level 0: 250 mg PO once daily / Dose level 1: 300 mg PO once daily
DRUG	Paclitaxel	Dose level -2: 60 mg/m2 IV on day 1, 8, and 15 / Dose level -1: 70 mg/m2 IV on day 1, 8, and 15 / Dose level 0: 70 mg/m2 IV on day 1, 8, and 15 / Dose level 1: 70 mg/m2 IV on day 1, 8, and 15

Timeline

• Start date: 2020-09-01
• Primary completion: 2023-06-01
• Completion: 2024-12-01
• First posted: 2020-08-25
• Last updated: 2021-08-24

Locations

2 sites across 1 country: South Korea

Regulatory

• FDA-regulated drug study