AZD2014 and Weekly Paclitaxel in Squamous NSCLC

NCT02403895 | Terminated Phase 2 Results

• 1 other identifier: D2274C00001
• Study Type: interventional
• Target: 11
• Locations: 3 countries
• Sites: 7

Brief 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)

Conditions

Squamous Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Who Have a Partial Response or Complete Response Through Measurement of Tumour Lesion Sizes

  Calculation of the percentage of patient who have a Complete Response or Partial Response to treatment which is confirmed by a repeat assessment 4 weeks later

  From first dose until disease progression (Approximately 3 months)

Secondary Outcomes (9)

• Number of Patients Who Experienced at Least One Adverse Event (AE) or Serious Adverse Event (SAE)

  Informed consent until end of safety follow up (Approx 10 months if all treatment cycles are completed)

• Overall Survival: Median Number of Days Between the First Dose and End of Life Due to Any Cause

  From first dose until end of life (Approx 9 months)

• Best Objective Response: Number of Patients Who Experienced a Best Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not-Evaluable (NE), Through Measurement of Tumour Lesion Sizes.

  From Baseline until Disease Progression (Approx 3 months)

• Duration of Response: Median Number of Days From the Date of First Documented Response Until the Date of Documented Progression Through Measurement of Tumour Lesion Sizes

  From date of first documented response until documented progression or end of life in the absence of progression (Approx 3 months)

• Disease Control Rate: Percentage of Patients Who Achieve Partial Response, Complete Response or Stable Disease Through Assessment of Tumour Lesion Sizes

  From first dose until documented progression and at least 6 weeks after the start of treatment for assessment of Stable Disease - Assessed at 6, 13 and 20 Weeks

Study Arms (1)

Open-label AZD2014

EXPERIMENTAL

Open-label AZD2014 given twice daily 3 days on, 4 days off during weekly paclitaxel

Drug: Open-label AZD2014; Drug: paclitaxel

Interventions

Open-label AZD2014 DRUG

Dual TORC1/TORC2 inhibitor

Open-label AZD2014

paclitaxel DRUG

Taxane

Open-label AZD2014

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven squamous non-small cell lung cancer (NSCLC) where treatment with weekly paclitaxel is an appropriate treatment option.
• 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.
• Measurable disease by RECIST v1.1 criteria
• Life expectancy of at least 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

You may not qualify if:

• 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.
• 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.
• Known leptomeningeal involvement, brain metastases or spinal cord compression.
• History of hypersensitivity (\> Grade 2) to active or inactive excipients of AZD2014, drugs containing Cremophor, taxanes or structurally/chemically similar drugs
• 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
• Patients with Diabetes Type I or uncontrolled Type II (HbA1c \> 59 mmol/mol assessed locally) as judged by the Investigator
• 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
• 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
• 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)

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (7)

Research Site

Boston, Massachusetts, 02215, United States

Location

Research Site

Detroit, Michigan, 48201, United States

Location

Research Site

Hershey, Pennsylvania, 17022, United States

Location

Research Site

Dallas, Texas, 75251, United States

Location

Research Site

Gauting, 82131, Germany

Location

Research Site

Barcelona, 08035, Spain

Location

Research Site

Girona, 17007, Spain

Location

MeSH Terms

Interventions

Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

Sponsor and Investigator decision was taken to terminate further recruitment into the study due to lack of observed responses rendering it futile to continue. As such, an abbreviated Clinical Study Report was produced based on data from 11 patients.

Results Point of Contact

• Title: Medical Science Director
• Organization: AstraZeneca

clinicaltrialtransparency@astrazeneca.com

Study Officials

• Chandra P Belani, MD

  Hershey Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2015
• First Posted: March 31, 2015
• Study Start: April 15, 2015
• Primary Completion: December 29, 2016
• Study Completion: December 29, 2016
• Last Updated: July 3, 2018
• Results First Posted: July 3, 2018

Record last verified: 2018-06

Locations

US (4); DE (1); ES (2)