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

NCT02771314 | Unknown Phase 2

• 1 other identifier: D5160C00030
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 13

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.

Conditions

Non Small Cell Lung Cancer

Keywords

NSCLC; AZD9291; >= 2nd line; liquid biopsy; EGFR TKIs; EGFR mutant

Outcome Measures

Primary Outcomes (1)

• 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)

  Up to 2.5 years

Secondary Outcomes (3)

• Progression free survival (PFS)

  Up to 2.5 years

• Overall Survival

  Up to 2.5 years

• Response rate, assessed using RECIST 1.1

  Up to 2.5 years

Study Arms (1)

AZD9291

EXPERIMENTAL

AZD9291

Drug: AZD9291

Interventions

AZD9291 DRUG

AZD9291, 80 mg (tablets) once daily, administered orally in the fasted state

Also known as: Tagrisso, Osimertinib

AZD9291

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hellenic Oncology Research Group: lead

Study Sites (13)

University Hospital of Heraklion Crete

Heraklion, Crete, 71110, Greece

Location

251 Air Forces Military Hospital of Athens

Athens, Greece

Location

Anticancer Hospital of Athens "Agios Savvas"

Athens, Greece

Location

Athens Hospital "Mitera" Hygia Polis

Athens, Greece

Location

General Hospital of Athens "Aretaieio"

Athens, Greece

Location

General Hospital of Athens "Evangelismos"

Athens, Greece

Location

General Oncology Hospital of Athens "Ag. Anargiroi"

Athens, Greece

Location

IASO General Hospital

Athens, Greece

Location

Universtiy Hospital of Athens "Attikon"

Athens, Greece

Location

University Hospital of Patra-Rio

Rio, 26504, Greece

Location

Diabalkaniko General Hospital of Thessaloniki

Thessaloniki, Greece

Location

General Hospital of Thesaloniki "G. Papanikolaou"

Thessaloniki, Greece

Location

Thessaloniki Bioclinic

Thessaloniki, Greece

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Athanasios Kotsakis, PhD

  Hellenic Oncology Research Group

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 12, 2016
• First Posted: May 13, 2016
• Study Start: August 2, 2016
• Primary Completion: June 1, 2020
• Study Completion: December 1, 2020
• Last Updated: February 22, 2019

Record last verified: 2019-02

Locations

GR (13)