NCT03745911

Paclitaxel and TAK-228 in Urothelial Carcinoma

Phase II Study of Paclitaxel and TAK-228 in Metastatic Urothelial Carcinoma (UC) and the Impact of PI3K-mTOR Pathway Genomic Alterations

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Sponsor: Associació per a la Recerca Oncologica, Spain · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Phase II Multicentre, single arm, open label study of Paclitaxel and TAK-228 in metastatic urothelial carcinoma (UC) and the impact of PI3K-mTOR pathway genomic alterations

Detailed description

The PI3K/AKT/mTOR pathway has been shown to be altered in a large percentage of metastatic urothelial carcinoma (UC) tumors. Within this pathway, the PI3 kinase alpha subunit (PIK3CA) is frequently mutated in muscle invasive bladder cancer (MIBC) (15-20%) and PTEN is inactivated in another 30%. Due to TAK-228's effects on the PI3K/AKT/mTOR pathway in preclinical studies and the frequency of pathway alterations in UC tumors, TAK-228 is a rational therapy for bladder cancer. This clinical investigation may also reveal how alterations in the PI3K/AKT/mTOR pathway correlate with treatment response. In preclinical bladder cell line models and xenografts done in our lab, synergistic effect has been seen with the combination with paclitaxel. The primary end-point is objective response rate (ORR) with the goal of increasing the rate from 10% to 26%. Response rates will be measured using RECIST 1.1 criteria. PFS and OS will be measured from the start date of treatment with TAK-228 and paclitaxel. Grade 3, 4 or serious adverse events will be collected and compared to the catalogued events in the phase II trial in breast cancer (NCT01351350). Patient tumors will be analyzed for genetic alterations within the PI3K/AKT/mTOR pathway to determine if alterations within this pathway correlate with response rate, PFS, or OS.

Conditions

• Metastatic Urothelial Cancer

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Paclitaxel and TAK-228	Treatment with TAK-228 oral (D2, 3 and 4 of each week) and paclitaxel (D1 of each week) on Days 1, 8 and 15 for each 28-days cycle until disease progression or unacceptable toxicity. If paclitaxel is stopped, TAK-228 may be continued

Timeline

• Start date: 2018-05-04
• Primary completion: 2020-11-01
• Completion: 2020-11-01
• First posted: 2018-11-19
• Last updated: 2018-11-19

Locations

5 sites across 1 country: Spain