A Phase I Trial of the Combination of AZD2014 and Weekly Paclitaxel. (TAX-TORC)
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|ClinicalTrials.gov Identifier: NCT02193633|
Recruitment Status : Unknown
Verified March 2015 by Royal Marsden NHS Foundation Trust.
Recruitment status was: Recruiting
First Posted : July 17, 2014
Last Update Posted : March 12, 2015
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.
|Condition or disease||Intervention/treatment||Phase|
|Advanced Cancer||Drug: AZD2014 3 on/4 off & weekly paclitaxel Drug: AZD2014 2 on/5 off & weekly paclitaxel||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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.|
|Study Start Date :||April 2013|
|Estimated Primary Completion Date :||December 2015|
|Estimated Study Completion Date :||December 2015|
Experimental: AZD2014 3 on/4 off & weekly paclitaxel
3 days on, 4 days off AZD2014 BD administered orally Days 1-3 each week in combination with paclitaxel administered via IV infusion on Day 1 each week, in 7-week cycles (6 weeks treatment followed by 1 week rest).
Drug: AZD2014 3 on/4 off & weekly paclitaxel
AZD2014 3 days on, 4 days off + weekly paclitaxel
Experimental: AZD2014 2 on/5 off & weekly paclitaxel
AZD2014 BD administered orally Days 1-2 each week in combination with paclitaxel administered via IV infusion on Day 1 each week, in 7-week cycles (6 weeks treatment followed by 1 week rest).
Drug: AZD2014 2 on/5 off & weekly paclitaxel
AZD2014 2 days on, 5 Days off + weekly paclitaxel
- Establish the maximum tolerated dose and recommended Phase II dose of two intermittent dosing schedules of AZD2014: 3 days on, 4 days off and 2 days on, 5 days off in combination with weekly paclitaxel in patients with solid tumours. [ Time Frame: First cycle of treamtent (7 weeks) ]To determine the dose at which no more than one patient out of up to 6 patients at the same dose level experience a drug-related dose-limiting toxicity.
- PK parameters for AZD2014 and paclitaxel derived from determining their plasma concentrations using validated assays. [ Time Frame: First cycle of treatment (7 weeks) ]To explore the effect of paclitaxel on the pharmacokinetics of AZD2014
- PK parameters for AZD2014 and paclitaxel derived from determining their plasma concentrations using validated assays [ Time Frame: First cycle of treatment (7 weeks) ]Investigate the pharmacodynamics behaviour of the combination of AZD2014 and paclitaxel.
- To document any possible anti-tumour activity [ Time Frame: Duration of the study ]To determine disease response by RECIST criteria version 1.1, GCIG CA125 criteria and change in tumour size.
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): NCT02193633
|Contact: Alison Turner, PhD||0208661 ext firstname.lastname@example.org|
|Contact: Nith Sathiyayogan, MSc||0208722 ext email@example.com|
|Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ|
|Principal Investigator: Bristi Basu|
|Royal Marsden Hospital||Recruiting|
|Sutton, Surrey, United Kingdom, SM2 5PT|
|Principal Investigator: Udai Banerji, PhD|
|Belfast City Hospital||Not yet recruiting|
|Belfast, United Kingdom, BT9 7AB|
|Principal Investigator: Richard Wilson|
|Guy's and St Thomas's NHS Foundation Trust||Recruiting|
|London, United Kingdom, SE1 9RT|
|Contact: James Spicer, MBBS, PhD +44 (0)20 7188 7344|
|Principal Investigator:||Udai Banerji, PhD||The Institute of Cancer Research, Royal Marsden NHS Foundation Trust|