Overview

This trial is active, not recruiting.

Condition squamous non small cell lung cancer
Treatments open-label azd2014, paclitaxel
Phase phase 2
Target mTOR
Sponsor AstraZeneca
Start date April 2015
End date May 2016
Trial size 11 participants
Trial identifier NCT02403895, D2274C00001

Summary

Open--label, phase 2a, multi-centre, single-arm study to assess the efficacy and safety of AZD2014 and weekly paclitaxel in patients with squamous non-small cell lung cancer (NSCLC)

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Open-label AZD2014 given twice daily 3 days on, 4 days off during weekly paclitaxel
open-label azd2014
Dual TORC1/TORC2 inhibitor
paclitaxel
Taxane

Primary Outcomes

Measure
Anti-tumour activity through calculation of the percentage of patients who have a Partial Response or Complete response through measurement of tumour lesion sizes
time frame: From first dose until disease progression (Approximately 3 months)

Secondary Outcomes

Measure
Number of patients experiencing adverse events (AE) and Serious Adverse Events (SAEs) including chemistry, haematology, vital signs and ECG variables
time frame: Informed consent until end of safety follow up (Approx 10 months if all treatment cycles are completed)
Duration of Overall Survival
time frame: From first dose until end of life (Approx 9 months)
Anti-tumour activity through assessment of Best Objective Response by assessment of tumour lesions
time frame: From Baseline until Disease Progression (Approx 3 months)
Anti-tumour activity through assessment of Duration of Response by assessment of tumour lesions
time frame: From date of first documented response until documented progression or end of life in the absence of progression (Approx 3 months)
Anti-tumour activity through assessment of Disease Control Rate by measurement of the number of patients who achieve Partial Response, Complete Response or Stable Disease through assessment of tumour lesions
time frame: From first dose until documented progression and at least 7 weeks after the start of treatment for assessment of Stable Disease (Approx 3 months)
Anti-tumour activity through assessment of percentage change in tumour size by measurement of tumour lesions
time frame: From baseline until documented progression (Approx 3 months)
Anti-tumour activity through assessment of duration of progression free survival by measurement of tumour lesions
time frame: From date of first dose until documented progression or end of life (Approx 3 months)
Evaluate the effect of the combination of AZD2014 and paclitaxel on pharmacokinetics which may include assessment of AUC (Area Under Curve) and levels of plasma concentration over time (Cmax, tmax, tlast, Cinf)
time frame: Assessment at multiple timepoints in Group A patients. Samples will be taken at pre-dose and at 10 further timepoints on day 1 and at pre-dose and 9 further timepoints on days 3 and 8
Estimated pharmacokinetic exposure to AZD2014 through the use of population PK modelling
time frame: Assessment at multiple timepoints in Group B patients between study day 1 and day 3. Samples will be taken at 3 points on day 1 and at predose and at a further 2 points on day 3

Eligibility Criteria

Male or female participants from 18 years up to 130 years old.

Inclusion Criteria: 1. Histologically or cytologically proven squamous non-small cell lung cancer (NSCLC) where treatment with weekly paclitaxel is an appropriate treatment option. 2. Relapsed or refractory disease after at least one line of prior therapy. Subjects must have previously received appropriate line(s) of standard of care (SOC) treatment. 3. Measurable disease by RECIST v1.1 criteria 4. Life expectancy of at least 12 weeks. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Exclusion Criteria: 1. Radiotherapy (except for palliative reasons), chemotherapy, endocrine therapy, or immunotherapy during the previous 3 weeks (4 weeks for investigational medicinal products and 6 weeks for nitrosoureas and Mitomycin-C) before treatment. 2. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or Grade 1 toxicities which, in the opinion of the Investigator, should not exclude the patient. 3. Known leptomeningeal involvement, brain metastases or spinal cord compression. 4. History of hypersensitivity (> Grade 2) to active or inactive excipients of AZD2014, drugs containing Cremophor, taxanes or structurally/chemically similar drugs 5. Current refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow formulated product or previous significant bowel resection that would preclude adequate absorption of AZD2014 6. Patients with Diabetes Type I or uncontrolled Type II (HbA1c > 59 mmol/mol assessed locally) as judged by the Investigator 7. Major surgery within 4 weeks prior to entry to the study (excluding placement of vascular access), or minor surgery within 2 weeks of entry into the study and from which the patient has not yet recovered 8. Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening (with the exception of pegylated G-CSF (pegfilgrastim) and darbepoetin which require at least 14 days prior to screening), defined as: - Absolute neutrophil count 1500 cells/mm3 (1.5 x 109/L) - Platelet count 100.000 cells/mm3 (100 x 109/L) - Haemoglobin 9.0 g/dL 9. Adequate hepatic and renal function defined as: - Serum aspartate transaminase (AST) or alanine transaminase (ALT) 2.5 x upper limit of normal (ULN) if no demonstrable liver metastases or 5 x ULN in the presence of liver metastases - Alkaline phosphatase (ALP) < 5 x ULN - Serum bilirubin 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin) - Estimated Creatinine Clearance 50 ml/min (Cockcroft-Gault) or serum creatinine 1.5 x ULN

Additional Information

Official title A Phase 2a, Multi-centre, Single-arm Trial of the Combination of AZD2014 and Weekly Paclitaxel in Patients With Relapsed or Refractory Squamous Non-Small Cell Lung Cancer After At Least One Line of Prior Therapy
Principal investigator Chandra P Belani, MD
Description This is an open-label, phase 2a, multi-centre, single-arm study to assess the efficacy and safety of the combination of AZD2014 and weekly paclitaxel in patients with squamous non-small cell lung cancer (NSCLC) that is relapsed or refractory to conventional treatment after at least 1 prior treatment with standard of care (SOC) and for whom weekly paclitaxel treatment is an appropriate treatment choice. The study will simultaneously enrol patients to the following two groups. Group A (intensive PK) will enrol 10 evaluable patients for an intra-patient evaluation of the impact of paclitaxel on exposure to AZD2014, and the impact of AZD2014 on exposure to paclitaxel via intensive PK sampling and non-compartmental PK analysis techniques (NCA). Group B (sparse PK) will enrol 30 patients and sparse sampling and population PK modelling techniques will be employed to estimate exposure to AZD2014 when administered in combination with a weekly paclitaxel dosing regimen. The efficacy and safety of the AZD2014 and weekly paclitaxel combination will be evaluated in all 40 patients using RECIST 1.1, observation of AEs/SAEs and use of conventional safety parameters. Eligible patients will receive study treatment consisting of a single weekly paclitaxel infusion (80 mg/m2) on Day 1 of each week and twice daily (BD) 50 mg doses of AZD2014 on the first 3 days each week for 6 weeks [except Group A patients in Week 1 of Cycle 1 who will take 50 mg BD doses of AZD2014 on Days 3, 4 and 5 (or Days 4, 5 and 6) to accommodate PK sampling], followed by a break from treatment when no paclitaxel or AZD2014 will be given. This 7-week schedule composes one cycle of treatment. AZD2014 will be administered as oral tablets to fasted patients (i.e., no food 2 hours before and 1 hour after each dose). Patients will receive up to 6 cycles of paclitaxel, although additional cycles of paclitaxel may be given if deemed appropriate by the Investigator.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.
Location data was received from the National Cancer Institute and was last updated in July 2016.