Phase Ib/II Study of LY2780301 in Combination With Weekly PACLITAXEL in HER2-metastatic Breast Cancer (TAKTIC)
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|ClinicalTrials.gov Identifier: NCT01980277|
Recruitment Status : Active, not recruiting
First Posted : November 8, 2013
Last Update Posted : June 28, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: LY2780301 + paclitaxel||Phase 1 Phase 2|
RATIONALE OF THE STUDY DESIGN
The purpose of this study will be:
- to determine the recommended phase 2 dose (RP2D) for LY2780301 in combination with weekly paclitaxel in HER2-negative, inoperable locally advanced or MBC patients
- 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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||68 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||January 2014|
|Actual Primary Completion Date :||May 2017|
|Estimated Study Completion Date :||December 2018|
Experimental: LY2780301 + paclitaxel
The following dose-levels will be investigated:
A dose reduction could be explored:
- Continuous daily PO LY2780301 300 mg QD + weekly paclitaxel 70 mg/m²/week
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
- Phase Ib: recommended phase II dose (RP2D) [ Time Frame: Day 28 ]To determine the recommended phase II dose (RP2D) of daily LY2780301 when administered orally in combination with weekly intravenous (IV) paclitaxel in HER2-negative, inoperable locally advanced or MBC patients
- Phase II: objective response rate (ORR) [ Time Frame: until progression assessed up to 18 months ]To estimate the efficacy of daily LY2780301 when administered orally at the RP2D in combination with weekly intravenous (IV) paclitaxel in HER2-negative, inoperable locally advanced or MBC patients, in the overall population and in patients with activation of PI3/AKT/S6 pathway
- safety [ Time Frame: up to the end of treatment or maximum 6 months ]Type and severity of adverse events according to CTCAE v4.0 up to the end of treatment or maximum 6 months
- clinical benefit (CB) [ Time Frame: until progression assessed up to 18 months ]The Clinical benefit (CB) is defined as the addition of complete response (CR) + partial response (PR) + Stable disease (SD) > 6 months
- progression-free survival (PFS) [ Time Frame: until progression assessed up to 18 months ]Date of progression (evaluated according to RECIST V1.1 criteria) or death up to 18 months
- pharmacokinetics [ Time Frame: D1, D8, D15, D22, D28 post dose ]Pharmacokinetics of LY2780301 and paclitaxel evaluated by plasma concentrations and basic PK parameters
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01980277
|Centre Geroges François Leclerd|
|Dijon, France, 21079|
|Marseille, France, 13008|
|Principal Investigator:||Anthony GONCALVES, MD||Institut Paoli-Calmettes|