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Liquid Biopsy as a Tool to Evaluate Resistance to First and Third (AZD9291) (EGFR) (TKIs) in (EGFR) Mutant NSCLC

Primary Purpose

Non Small Cell Lung Cancer

Status
Unknown status
Phase
Phase 2
Locations
Greece
Study Type
Interventional
Intervention
AZD9291
Sponsored by
Hellenic Oncology Research Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Non Small Cell Lung Cancer focused on measuring NSCLC, AZD9291, >= 2nd line, liquid biopsy, EGFR TKIs, EGFR mutant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age >18 years
  2. Both sexes
  3. Histologically or cytologically documented NSCLC
  4. Stage 3b (IIIb) not amenable to radical therapy or stage IV
  5. Presence of EGFR activating mutations (exon 19 deletion or L858R in exon 21)
  6. First or second line treatment with EGFR TKIs
  7. Performance status (ECOG): 0-1
  8. Measurable or evaluable disease
  9. Adequate organ function tests (Hb>=10g/dL, white blood cell (WBC) >=3.0 x 10^9/L, neutrophils count >=1.5 x 10^9/L, platelets≥100 x 10^9/L, Creatinine clearance >=50 mL/min, Total bilirubin=<1.5 X UNL, aspartate aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline phosphatase (ALP) =<2.5 x UNL)
  10. Normal QT interval in ECG
  11. Central nervous system (CNS) metastases are allowed provided that they have been irradiated and the patient is clinically stable
  12. Women of child bearing potential and all men will be required to use adequate contraceptive measures
  13. Life expectancy of at least 3 months
  14. Written informed consent

Exclusion Criteria:

  1. History of serious drug allergy
  2. Refractory nausea, vomiting and chronic gastrointestinal diseases

  3. Any of the following cardiac criteria:

    • Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value.
    • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
    • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
  4. Severe or uncontrolled systemic liver disease, including those with known hepatitis B, hepatitis C, and Human Immunodeficiency virus (HIV) infection
  5. Interstitial lung disease or pulmonary fibrosis
  6. Pregnancy, lactation or other concomitant serious medical condition
  7. Other concurrent active malignancy

Sites / Locations

  • University Hospital of Heraklion Crete
  • 251 Air Forces Military Hospital of Athens
  • Anticancer Hospital of Athens "Agios Savvas"
  • Athens Hospital "Mitera" Hygia Polis
  • General Hospital of Athens "Aretaieio"
  • General Hospital of Athens "Evangelismos"
  • General Oncology Hospital of Athens "Ag. Anargiroi"
  • IASO General Hospital
  • Universtiy Hospital of Athens "Attikon"
  • University Hospital of Patra-Rio
  • Diabalkaniko General Hospital of Thessaloniki
  • Thessaloniki Bioclinic
  • General Hospital of Thesaloniki "G. Papanikolaou"

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AZD9291

Arm Description

AZD9291

Outcomes

Primary Outcome Measures

Biomarkers of resistance to first and third (AZD9291) generation EGFR TKIs, explored by studying baseline serial serum or plasma DNA specimens and baseline Circulating Tumor Cells (CTCs)

Secondary Outcome Measures

Progression free survival (PFS)
Overall Survival
Response rate, assessed using RECIST 1.1

Full Information

First Posted
April 12, 2016
Last Updated
February 20, 2019
Sponsor
Hellenic Oncology Research Group
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1. Study Identification

Unique Protocol Identification Number
NCT02771314
Brief Title
Liquid Biopsy as a Tool to Evaluate Resistance to First and Third (AZD9291) (EGFR) (TKIs) in (EGFR) Mutant NSCLC
Official Title
A Longitudinal Study Evaluating Molecular Changes Associated With Resistance to First and Third (AZD9291) Generation EGFR TKIs in Patients With EGFR Mutant NSCLC Using "Liquid Biopsy"
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Unknown status
Study Start Date
August 2, 2016 (Actual)
Primary Completion Date
June 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hellenic Oncology Research Group

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Based on the possibilities that both plasma and circulating tumor cells (CTCs) (the "liquid biopsy") may offer, we consider that it could be feasible to longitudinally monitor the genetic evolution and the biologic characteristics of CTCs, by using Circulating tumor DNA (ctDNA) and CTCs as a source of biologic material. This approach could provide information regarding the genetic/molecular changes associated with primary and acquired resistance to AZD9291 and, thus, to facilitate to more appropriately adapt the tailored treatment in this particular group of NSCLC patients. It has been recently reported that the detection of resistant clones, based on the tumor-associated genetic aberrations in the blood, can identify treatment resistance up to 10 months earlier than the radiological methods providing, thus, the potential for an early switch to a non cross-resistant therapy in order to improve patients' outcome.
Detailed Description
Lung cancer is among the most common tumor types representing 13% of the newly diagnosed cancers worldwide. Both the absolute and relative frequency of lung cancer has risen dramatically. Unfortunately, lung cancer remains by far the leading cause of cancer-related deaths, accounting for 18% of the total number of deaths. Non Small Lung Cancer (NSCLC) accounts for 85% of all cases of lung cancer and is further classified in several subtypes based on various molecular and histological features. The initial dose of 80 mg AZD9291 administered once daily orally in the fasted state can be reduced to 40 mg AZD9291 once daily under circumstances Single arm, open-label, phase II, multicenter study. NSCLC patients with activating EGFR mutations, who are under front line treatment with first generation EGFR TKIs according to the physicians' choice and present disease progression, will be treated with single agent AZD9291. The patients will be followed every 3 months for the detection of mutations (T790M), (C797S), (L858R), del 19 EGFR mutations as well as the mutations [(KRAS)/(NRAS), (BRAF), (PI3K)] in the serum/plasma, the determination of the serum levels of Hepatocyte Growth Factor (HGF), the presence of T790M (+) and C797S(+) CTCs as well as the molecular (c-MET) and (HER2 amplification) and phenotypic characterization of CTCs using the filtration platform (ISET). The elimination or the emergence of each of these circulating tumor biomarkers will be correlated with patients' clinical outcome [objective response to treatment (ORR), (PFS) and (OS)]. There is no specific control group in this study. Biomarkers profile at baseline will be used as internal control for each patient to monitor changes throughout treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer
Keywords
NSCLC, AZD9291, >= 2nd line, liquid biopsy, EGFR TKIs, EGFR mutant

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AZD9291
Arm Type
Experimental
Arm Description
AZD9291
Intervention Type
Drug
Intervention Name(s)
AZD9291
Other Intervention Name(s)
Tagrisso, Osimertinib
Intervention Description
AZD9291, 80 mg (tablets) once daily, administered orally in the fasted state
Primary Outcome Measure Information:
Title
Biomarkers of resistance to first and third (AZD9291) generation EGFR TKIs, explored by studying baseline serial serum or plasma DNA specimens and baseline Circulating Tumor Cells (CTCs)
Time Frame
Up to 2.5 years
Secondary Outcome Measure Information:
Title
Progression free survival (PFS)
Time Frame
Up to 2.5 years
Title
Overall Survival
Time Frame
Up to 2.5 years
Title
Response rate, assessed using RECIST 1.1
Time Frame
Up to 2.5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age >18 years Both sexes Histologically or cytologically documented NSCLC Stage 3b (IIIb) not amenable to radical therapy or stage IV Presence of EGFR activating mutations (exon 19 deletion or L858R in exon 21) First or second line treatment with EGFR TKIs Performance status (ECOG): 0-1 Measurable or evaluable disease Adequate organ function tests (Hb>=10g/dL, white blood cell (WBC) >=3.0 x 10^9/L, neutrophils count >=1.5 x 10^9/L, platelets≥100 x 10^9/L, Creatinine clearance >=50 mL/min, Total bilirubin=<1.5 X UNL, aspartate aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline phosphatase (ALP) =<2.5 x UNL) Normal QT interval in ECG Central nervous system (CNS) metastases are allowed provided that they have been irradiated and the patient is clinically stable Women of child bearing potential and all men will be required to use adequate contraceptive measures Life expectancy of at least 3 months Written informed consent Exclusion Criteria: History of serious drug allergy Refractory nausea, vomiting and chronic gastrointestinal diseases Any of the following cardiac criteria: Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval. Severe or uncontrolled systemic liver disease, including those with known hepatitis B, hepatitis C, and Human Immunodeficiency virus (HIV) infection Interstitial lung disease or pulmonary fibrosis Pregnancy, lactation or other concomitant serious medical condition Other concurrent active malignancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Athanasios Kotsakis, PhD
Organizational Affiliation
Hellenic Oncology Research Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital of Heraklion Crete
City
Heraklion
State/Province
Crete
ZIP/Postal Code
71110
Country
Greece
Facility Name
251 Air Forces Military Hospital of Athens
City
Athens
Country
Greece
Facility Name
Anticancer Hospital of Athens "Agios Savvas"
City
Athens
Country
Greece
Facility Name
Athens Hospital "Mitera" Hygia Polis
City
Athens
Country
Greece
Facility Name
General Hospital of Athens "Aretaieio"
City
Athens
Country
Greece
Facility Name
General Hospital of Athens "Evangelismos"
City
Athens
Country
Greece
Facility Name
General Oncology Hospital of Athens "Ag. Anargiroi"
City
Athens
Country
Greece
Facility Name
IASO General Hospital
City
Athens
Country
Greece
Facility Name
Universtiy Hospital of Athens "Attikon"
City
Athens
Country
Greece
Facility Name
University Hospital of Patra-Rio
City
Río
ZIP/Postal Code
26504
Country
Greece
Facility Name
Diabalkaniko General Hospital of Thessaloniki
City
Thessaloniki
Country
Greece
Facility Name
Thessaloniki Bioclinic
City
Thessaloniki
Country
Greece
Facility Name
General Hospital of Thesaloniki "G. Papanikolaou"
City
Thessaloníki
Country
Greece

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Liquid Biopsy as a Tool to Evaluate Resistance to First and Third (AZD9291) (EGFR) (TKIs) in (EGFR) Mutant NSCLC

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