T790M Plasma Testing Methodology Comparison and Clinical Validation

Lung Cancer Clinical Trial

— ADELOS  

Official title:

Detect EGFR T790M Mutation in ctDNA of Chinese Advanced/Metastatic NSCLC Patients by Cobas, Super-ARMS, Digital PCR and NGS and Evaluate Clinical Outcomes of T790M Mutation Positive Patients Who Had AZD9291 Monotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02997501
• Other study ID #: D5160C00042
• Status: Completed
• Phase: Phase 3
• Start date: December 23, 2016
• Est. completion date: October 24, 2018

Study information

• Verified date: February 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to evaluate concordance of T790M mutation plasma testing between the Cobas test and each of other platforms: Super-ARMS, digital PCR or NGS. And to assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.

Description:

Objective: The primary objective of this study is to evaluate concordance of T790M mutation plasma testing between the Cobas test and each of other platforms: Super-ARMS, digital PCR or NGS. And to assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.

Study number of patients planned: Approximately 250 patients will be recruited in China.

Study Design: This is an open-label, multi-center testing and treatment study.

Target patient population: 250 locally advanced or metastatic EGFR mutation positive NSCLC patients with progression on a previous EGFR-TKI will be recruited.

Investigational product (IP), dosage, and mode of administration: AZD9291 is an oral, potent, selective, irreversible inhibitor of both EGFR-TKI sensitizing and resistance mutations in NSCLC with a significant selectivity margin over wild-type EGFR. AZD9291 will be administered orally as one 80 mg tablet once a day. All AEs/SAEs would be reported in ASTRIS main study and would not be reported repeatedly in current study.

Duration of IP administration: Patients may continue to receive AZD9291 as long as they continue to show clinical benefit, as judged by the investigator, and in the absence of discontinuation criteria. The study will be closed in a maximum period of 18 months after the last patient is enrolled. Contingencies will be made to ensure continued drug supply for patients who are still deriving benefit from AZD9291 at that time.

Study measures: Data collected will include patient demographics, smoking history, information needed to determine patient eligibility (including medical history, past and current disease characteristics, and tumor EGFR mutations status, T790M and sensitizing mutations status results and type of test performed), AZD9291 exposure, investigator-reported efficacy (including tumor response and disease progression), overall survival (OS).

Statistical methods: The concordance of T790M resistance mutation testing between the Cobas test and each of other platforms will be calculated. The sensitivity, specificity, PPV and NPV of each testing platform (Super-ARMS, digital PCR, and NGS) will be calculated with the Cobas test as the reference. The Kappa coefficient will be calculated to measure the agreement of T790M mutation testing between the Cobas test and each of other platforms. Descriptive statistics will be provided for all variables, as appropriate. Continuous variables will be summarized by the number of observations, mean, standard deviation, median, interquartile range (Q1, Q3), minimum, and maximum. Categorical variables will be summarized by frequency counts and percentages for each category. The 95% confidence interval (CI) will be calculated as appropriate. PFS and OS, respectively, will be summarized using Kaplan-Meier estimates of the median time to event (progression and death) and quartiles together with their 95% confidence intervals.The chi-square test will be used to compare the sensitivity, specificity, and concordance between any of the two platforms using Cobas as reference testing in an exploratory manner.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 256
• Est. completion date: October 24, 2018
• Est. primary completion date: October 24, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures.

2. Adults (according to China regulations for age of majority)

3. Histological or cytological confirmed locally advanced NSCLC (stage IIIB) or metastatic (stage IV) NSCLC, not amenable to curative surgery or radiotherapy.

4. Patients who have progressed following prior therapy with an EGFR-TKI agent.

Exclusion Criteria:

1. Patients who disagree to participate this study.

2. Patients whose medical objection was recorded to use the existing data from medical practice for scientific research.

Related Conditions & MeSH terms

• Lung Cancer

Intervention

Procedure:
• T790M+ Testing
The patient will need to have T790M+ testing
• Baseline Visit Blood & Urine Testing
Blood count and standard chemistry testing to ensure patient meets inclusion/exclusion criteria
• Baseline ECG
ECG to ensure absence of any cardiac abnormality
• Visual Slit-Lamp Testing
Slit-lamp testing performed to ensure patients do not have any eye abnormalities or symptoms

Drug:
• AZD9291 Dosing
Patients to be provided with AZD9291 every 6 weeks (+/- 7 days)

Procedure:
• Plasma AZD9291 testing
The patient will need to have plasma AZD9291 testing before treatment

Locations

Country	Name	City	State
China	Research Site	Changchun
China	Research Site	Chengdu
China	Research Site	Guangzhou
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xi'an

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	TigerMed

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concordance	To evaluate concordance of T790M plasma mutation testing between the Cobas test and each of other platforms: Super-ARMS, digital PCR or NGS.	Up to 6 months
Primary	PFS Using Investigator Assessments According to RECIST v1.1	To assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR- TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms. PFS was defined using Response Evaluation Criteria In Solid Tumors version 1.1(RECIST v1.1).	The time from first dose of AZD9291 in this study until the date of disease progression as recorded in CRF or death (by any cause in the absence of progression), assessed up to 18 months
Secondary	Testing Sensitivity, Specificity, PPV, NPV	To evaluate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Super-ARMS/digital PCR/NGS by using Cobas as the reference.	Up to 6 months.
Secondary	Overall Response Rate (ORR)	To assess the efficacy of AZD9291 monotherapy by assessment of ORR in adult patients who have received prior EGFR-TKI therapy and are EGFR T790M mutation positive detected by any one of the four plasma testing platforms. ORR is defined as the percentage of patients with measurable disease with at least 1 visit response of CR or PR. Data obtained until progression or last evaluable assessment in the absence of progression will be included in the assessment of ORR.	From first patient first CT scan for RECIST assessment, till the last patient last CT scan, up to 22 months.
Secondary	75% OS Duration	To assess the efficacy of AZD9291 monotherapy by assessment of overall survival (OS) in adult patients who have received prior EGFR-TKI therapy and are EGFR T790M mutation positive detected by any one of the four plasma testing platforms. 75% OS duration was calculated.	From first patient signed the consent to study completion, up to 22 months.

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