A Phase I Trial of the Combination of AZD2014 and Weekly Paclitaxel. — TAX-TORC  

Advanced Cancer Clinical Trial

Official title: TAX-TORC: A Phase I Multi-centre Trial of the Combination of AZD2014 (Dual mTORC1 and mTORC2 Inhibitor) and Weekly Paclitaxel in Patients With Solid Tumours.

Status Completed

Clinical Trial Summary

This is a Phase I study to evaluate the safety and toxicity profile of AZD2014, a novel anticancer agent, in combination with paclitaxel.

AZD2014 will be given orally, twice daily at a starting dose of 25 mg per day for 3 days on, 4 days off with a weekly infusion of 80 mg of paclitaxel for 6 weeks followed by a treatment break of one week, therefore each cycle will be 7 weeks long. Cohorts of three patients will be treated at this dose of AZD2014 and then at 50mg and 75 mg providing is it safe to do so. Once we have determined the maximum tolerated dose (MTD) using the 3 days on, 4 days off schedule of AZD2014, patients will be given AZD2014 2 days on, 5 days with their paclitaxel infusion. Patients will be enrolled in cohorts of three to evaluate three escalating doses of AZD2014 to determine the MTD for the 2 days on, 5 days off schedule.

On completion of the dose escalation phase of the study patients with ovarian cancer and squamous cell lung cancer will be treated at the MTD established for each dosing schedule. A minimum of 10 ovarian cancer patients and 15 squamous cell lung patients will be enrolled to the 3 days on, 4 days off schedule. Whilst a minimum of 10 squamous cell cancer patients will be enrolled to the 2 days on, 5 days off schedule to further assess the tolerability of the combination of AZD2014 and paclitaxel.

Clinical Trial Description

This is a multi-centre, Phase I clinical trial of the combination of AZD2014 and weekly paclitaxel.

Two intermittent BD dosing schedules of AZD2014 in combination with paclitaxel will be evaluated. The 3 days on 4 days off schedule will examine 3 continuous days of AZD2014 per week in combination with weekly paclitaxel. The 2 days on 5 days off schedule will examine 2 sequential days of AZD2014 dosing in combination with weekly paclitaxel. For both schedules, a dose escalation 3+3 design will be used to establish the MTD and the recommended Phase II dose. Approximately 15 patients with solid tumours will be entered into each schedule during the dose escalation of this phase.

The expansion part of the trial will be used to further assess the tolerability of AZD2014 in combination with weekly paclitaxel. For the 3 days on 4 days off schedule 10 patients with ovarian cancer and 15 patients with squamous lung cancer will be enrolled and treated at the MTD established from the dose escalation phase. Accrual to these expansion arms may commence as soon as the MTD is determined and proceed in parallel with the dose escalation phase of the 2 days on 5 days off schedule. Once the MTD has been determined for the 2 days on 5 days off schedule 15 patients with squamous lung cancer may be enrolled.

Determination of the MTD and decision to enter the expansion phase for each schedule will be made by the Safety Review Committee (SRC) taking into consideration the safety data and available PK/PD data. ;

Related Conditions & MeSH terms

• Advanced Cancer

• NCT number: NCT02193633
• Study type: Interventional
• Source: Royal Marsden NHS Foundation Trust
• Status: Completed
• Phase: Phase 1
• Start date: April 26, 2013
• Completion date: November 15, 2017