A Phase I Trial of the Combination of AZD2014 and Weekly Paclitaxel.
Condition: Advanced Cancer
Study type: Interventional
Phase: Phase 1

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.
    

Detailed 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.
    

Intervention name(s): AZD2014 3 on/4 off & weekly paclitaxel; AZD2014 2 on/5 off & weekly paclitaxel
Intervention type(s): Drug; Drug
Intervention description(s): AZD2014 3 days on, 4 days off + weekly paclitaxel; AZD2014 2 days on, 5 Days off + weekly paclitaxel
Other intervention name(s): AZD2014; AZD2014 3 days on, 4 days off; Paclitaxel; AZD2014; AZD2014 2 days of, 5 days off; Paclitaxel
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment