NCT01980277

Phase Ib/II Study of LY2780301 in Combination With Weekly PACLITAXEL in HER2-metastatic Breast Cancer

A Prospective, Multicentre, Uncontrolled, Phase Ib/II Study of LY2780301 in Combination With Weekly Paclitaxel in HER2-negative Metastatic or Locally Advanced Breast Cancer in Patients With and Without PI3/AKT/S6 Pathway Activation. - TAKTIC-IPC 2012-008

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 68 (estimated)
• Sponsor: Institut Paoli-Calmettes · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The overall rationale of this study evaluating tolerance and efficacy of LY2780301 in combination with paclitaxel in HER2-negative, inoperable locally advanced or metastatic breast cancer (MBC) is based on : * the medical need in this population with either hormonal-resistant or unsensitive and/or rapidly progressive disease * the preclinical evidences for involvement of PI3K/AKT pathway in tumor progression and drug resistance, including taxanes as well as its potential reversion by AKT inhibition * the high level of frequency of PI3K/AKT activation in HER2-negative MBC * the in vitro and in vivo preclinical activity of LY2780301, and its synergistic combination with various anticancer agents, including taxanes * the favourable profile of tolerance of LY2780301 in phase I trial Weekly paclitaxel is conventionally administered at 80 mg/m²/week and is a standard treatment in breast cancer (BC) As described above, LY2780301 500 mg once daily has been established as the RP2D in phase I single agent trial. Evidence of pharmacodynamic activity was noted at 400-500 mg QD. Conservatively, the first dose level to be explored will be LY2780301 400 mg QD and paclitaxel 70 mg/m²/week.

Detailed description

RATIONALE OF THE STUDY DESIGN The purpose of this study will be: 1. to determine the recommended phase 2 dose (RP2D) for LY2780301 in combination with weekly paclitaxel in HER2-negative, inoperable locally advanced or MBC patients 2. to estimate the objective response rate (ORR) of the combination in first-line treated, HER2-negative, inoperable locally advanced or MBC patients. In addition, this study will assess the role of PI3K/AKT/S6 pathway activation as potential predictive factor for response to LY2780301 in this patient population. This trial will be a phase Ib/II prospective, multicentre, open label, uncontrolled study. Phase Ib will use a continuous reassessment method (CRM) design, allowing to reach safely and quickly the MTD and the RP2D of the combination, but ensuring the treatment of at least 18 patients to secure the tolerance profile. Phase II will estimate antitumor activity in the overall patient population and in patients with activation of PI3K/AKT/S6 axis, allowing to examine its potential value as predictive biomarker

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	LY2780301 + paclitaxel	Continuous daily PO LY2780301 (400 mg, 500 mg or 300 mg) QD + weekly paclitaxel (70 or 80 mg/m²/week) for 21 days cycle until progression or toxicity

Timeline

• Start date: 2014-01-01
• Primary completion: 2017-05-01
• Completion: 2018-12-12
• First posted: 2013-11-08
• Last updated: 2019-01-23

Locations

2 sites across 1 country: France