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

• Status: Unknown status
• Trial end date: 2020-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hellenic Oncology Research Group
• Treatments: Osimertinib

Criteria

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