Liquid Biopsy as a Tool to Evaluate Resistance to First and Third (AZD9291) (EGFR) (TKIs) in (EGFR) Mutant NSCLC
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| ClinicalTrials.gov Identifier: NCT02771314 |
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Recruitment Status : Unknown
Verified February 2019 by Hellenic Oncology Research Group.
Recruitment status was: Active, not recruiting
First Posted : May 13, 2016
Last Update Posted : February 22, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non Small Cell Lung Cancer | Drug: AZD9291 | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 48 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Other |
| 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" |
| Actual Study Start Date : | August 2, 2016 |
| Estimated Primary Completion Date : | June 2020 |
| Estimated Study Completion Date : | December 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: AZD9291
AZD9291
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Drug: AZD9291
AZD9291, 80 mg (tablets) once daily, administered orally in the fasted state
Other Names:
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- 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 ]
- Progression free survival (PFS) [ Time Frame: Up to 2.5 years ]
- Overall Survival [ Time Frame: Up to 2.5 years ]
- Response rate, assessed using RECIST 1.1 [ Time Frame: Up to 2.5 years ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02771314
| Greece | |
| University Hospital of Heraklion Crete | |
| Heraklion, Crete, Greece, 71110 | |
| 251 Air Forces Military Hospital of Athens | |
| Athens, Greece | |
| Anticancer Hospital of Athens "Agios Savvas" | |
| Athens, Greece | |
| Athens Hospital "Mitera" Hygia Polis | |
| Athens, Greece | |
| General Hospital of Athens "Aretaieio" | |
| Athens, Greece | |
| General Hospital of Athens "Evangelismos" | |
| Athens, Greece | |
| General Oncology Hospital of Athens "Ag. Anargiroi" | |
| Athens, Greece | |
| IASO General Hospital | |
| Athens, Greece | |
| Universtiy Hospital of Athens "Attikon" | |
| Athens, Greece | |
| University Hospital of Patra-Rio | |
| Río, Greece, 26504 | |
| Diabalkaniko General Hospital of Thessaloniki | |
| Thessaloniki, Greece | |
| Thessaloniki Bioclinic | |
| Thessaloniki, Greece | |
| General Hospital of Thesaloniki "G. Papanikolaou" | |
| Thessaloníki, Greece | |
| Principal Investigator: | Athanasios Kotsakis, PhD | Hellenic Oncology Research Group |
| Responsible Party: | Hellenic Oncology Research Group |
| ClinicalTrials.gov Identifier: | NCT02771314 |
| Other Study ID Numbers: |
D5160C00030 |
| First Posted: | May 13, 2016 Key Record Dates |
| Last Update Posted: | February 22, 2019 |
| Last Verified: | February 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
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NSCLC AZD9291 >= 2nd line |
liquid biopsy EGFR TKIs EGFR mutant |
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Carcinoma, Non-Small-Cell Lung Carcinoma, Bronchogenic Bronchial Neoplasms Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms |
Lung Diseases Respiratory Tract Diseases Osimertinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |