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Report for Clinical Trial NCT04035486

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase III, Open-label, Randomized Study of Osimertinib With or Without Platinum Plus Pemetrexed Chemotherapy, as First-line Treatment in Patients With Epidermal Growth Factor Receptor (EGFR) Mutation Positive, Locally Advanced Non-Small Cell Lung Cancer (FLAURA2)

The reason for the study is to find out if an experimental combination of an oral medication called osimertinib (TAGRISSO®) when used in combination with chemotherapy is more effective than giving osimertinib alone for the treatment of locally advanced or metastatic non-small cell lung cancer. Some lung cancers are due to mutations in the Deoxyribonucleic acid (DNA) which, if known, can help physicians decide the best treatment for their patients. One type of mutation can occur in the gene that produces a protein on the surface of cells called the Epidermal Growth Factor Receptor (EGFR). Osimertinib is an Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets Epidermal Growth Factor Receptor (EGFR) mutations. Unfortunately, despite the benefit observed for patients treated with osimertinib, the vast majority of cancers are expected to develop resistance to the drug over time. The exact reasons why resistance develops are not fully understood but based upon clinical research it is hoped that combining osimertinib with another type of anti-cancer therapy known as chemotherapy will delay the onset of resistance and the worsening of a patient's cancer. In total the study aims to enroll approximately 586 patients, consisting of approximately 30 patients who will participate in a safety run-in component of the trial, and approximately 556 who will receive osimertinib alone or osimertinib in combination with chemotherapy in the main trial. In the main part of the trial there is a one in two chance of receiving osimertinib alone, and the treatment is decided at random by a computer. The study involves a Screening Period, Treatment Period, and Follow up Period. Whilst receiving study medication, it is expected patients will attend, on average, approximately 15 visits over the first 12 months and then approximately 4 visits per year afterwards. Each visit will last about 2 to 6 hours depending on the arrangement of medical assessments by the study centre.

NCT04035486 Non-Small Cell Lung Cancer
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

3 Interventions

Name: Osimertinib

Description: Drug: Osimertinib (Oral) Other Names: AZD9291
Type: Drug
Group Labels: 1

Osimertinib 80mg QD

Name: Pemetrexed/Carboplatin

Description: Drug: Pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.
Type: Drug
Group Labels: 1

Osimertinib 80 mg QD and platinum-based chemotherapy

Name: Pemetrexed/Cisplatin

Description: Drug: Pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.
Type: Drug
Group Labels: 1

Osimertinib 80 mg QD and platinum-based chemotherapy


Primary Outcomes

Description: Progression-free survival (PFS) using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Progression-free survival (PFS) is defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable Response Evaluation Criteria in Solid Tumors (RECIST) assessment. The primary efficacy analysis of progression-free survival will be performed by investigator assessment Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). An additional sensitivity analysis will be performed for Progression-free survival (PFS) by Blinded Independent Central Review (BICR) assessment.

Measure: Progression-free survival (PFS)

Time: The primary analysis of Progression-free survival (PFS) based on investigator assessment will occur when PFS maturity is observed at approximately 33 months after the first patient is randomized.

Secondary Outcomes

Description: Overall survival is defined as the time from the date of randomization until death due to any cause.

Measure: Overall Survival (OS)

Time: Overall Survival will be analyzed at 2 time points: when PFS maturity is observed at approximately 33 months after the first patient is randomized, and when OS maturity is observed at approximately 70 months after the first patient is randomized

Description: Landmark Overall Survival at 1, 2, and 3 years will look at the number of patients alive at 1, 2 and 3 year time points.

Measure: Landmark Overall Survival (LOS)

Time: The analysis of Landmark Overall Survival will be conducted at 2 time points: when PFS maturity is observed at approximately 33 months, and when Overall Survival maturity is observed at approximately 70 months after the first patient is randomized.

Description: Objective Response Rate (ORR) (per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) using Investigator assessments) is defined as the number (%) of patients with at least 1 visit response of Complete Response or Partial Response. Data obtained up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of Objective Response Rate

Measure: Objective Response Rate (ORR)

Time: Objective Response Rate analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 33 months from the first patient being randomized.

Description: Duration of Response is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.

Measure: Duration of Response (DoR)

Time: Duration of Response analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 33 months from the first patient being randomized.

Description: Depth of response (ie. tumor shrinkage / change in tumor size) by Investigator is defined as the relative change in the sum of the longest diameters of Response Evaluation Criteria in Solid Tumors (RECIST) target lesions at the nadir in the absence of New Lesions (NLs) or progression of Non-Target Lesions when compared to baseline.

Measure: Depth of Response

Time: Depth of Response analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 33 months from the first patient being randomized.

Description: Disease control rate (DCR) is defined as the percentage of subjects who have a best overall response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by the Investigator.

Measure: Disease Control Rate (DCR) by Investigator

Time: Disease Control Rate analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 33 months from the first patient being randomized.

Description: Progression Free Survival 2 is defined as the time from the date of randomization to the earliest of the progression events subsequent to that used for the primary Progression Free Survival (PFS), or death in absence of a first or second progression. The second progression event must have occurred after subsequent treatment administered after the initial progression free survival event.

Measure: Progression Free Survival 2 (PFS2)

Time: Progression Free Survival 2 analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 33 months from the first patient being randomized.

Description: Assess disease-related symptoms and health related Quality of Life (QoL) in patients treated with osimertinib plus chemotherapy compared with osimertinib.

Measure: Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items (EORTC QLQ-C30)

Time: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -Core 30 items analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 33 months from the first patient being randomized.

Description: Assess disease-related symptoms and health related Quality of Life (QoL) in patients treated with osimertinib plus chemotherapy compared with osimertinib.

Measure: Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items (EORTC QLQ-LC13)

Time: European Organization for Research & Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 33 months from the first patient being randomized

Description: Compare the local epidermal growth factor receptor mutation test result used for patient selection with the retrospective central cobas® epidermal growth factor receptor Mutation Test v2 results from baseline tumor samples.

Measure: Concordance of epidermal growth factor receptor mutation status between the local epidermal growth factor receptor mutation test and the central cobas® epidermal growth factor receptor Mutation Test v2 results from tumor samples with evaluable results

Time: Analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 33 months from the first patient being randomized.

Description: Determine efficacy of osimertinib monotherapy vs. osimertinib combined with chemotherapy based on the cobas® epidermal growth factor receptor mutation Test v2 plasma screening test result for Exon 19 deletions or Exon 21 (L858R) epidermal growth factor receptor mutations.

Measure: Progression-free survival (PFS) by Investigator by plasma epidermal growth factor receptor mutation status.

Time: Analysis will occur when Progression-free survival (PFS)maturity is observed at approximately 33 months from the first patient being randomized.

Description: An analysis will be performed to assess whether the plasma concentration of osimertinib is affected when given with or without chemotherapy. Samples will be collected pre-dose and 1-hour post-dose on day 22 and day 106; on day 43 samples will be collected pre-dose and 1, 2, 4, and 6 hours post-dose.

Measure: Plasma concentration of osimertinib when given with or without chemotherapy

Time: Plasma concentration analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 33 months from the first patient being randomized.

Description: An analysis will be performed to assess whether the plasma concentration of metabolite AZ5104 is affected when given with or without chemotherapy. Samples will be collected pre-dose and 1-hour post-dose on day 22 and day 106; on day 43 samples will be collected pre-dose and 1, 2, 4, and 6 hours post-dose.

Measure: Plasma concentration of metabolite AZ5104 when osimertinib is given with or without chemotherapy

Time: Plasma concentration analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 33 months from the first patient being randomized.

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 2 SNPs

SNPs


1 L858R

Compare the local epidermal growth factor receptor mutation test result used for patient selection with the retrospective central cobas® epidermal growth factor receptor Mutation Test v2 results from baseline tumor samples.. Progression-free survival (PFS) by Investigator by plasma epidermal growth factor receptor mutation status.. Determine efficacy of osimertinib monotherapy vs. osimertinib combined with chemotherapy based on the cobas® epidermal growth factor receptor mutation Test v2 plasma screening test result for Exon 19 deletions or Exon 21 (L858R) epidermal growth factor receptor mutations.. Plasma concentration of osimertinib when given with or without chemotherapy. --- L858R ---

4. The tumor harbors 1 of the 2 common epidermal growth factor receptor (EGFR) mutations known to be associated with Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) sensitivity (Ex19del or L858R), either alone or in combination with other epidermal growth factor receptor (EGFR) mutations, which may include T790M. 5. Patients must have untreated advanced Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy. --- L858R ---


2 T790M

4. The tumor harbors 1 of the 2 common epidermal growth factor receptor (EGFR) mutations known to be associated with Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) sensitivity (Ex19del or L858R), either alone or in combination with other epidermal growth factor receptor (EGFR) mutations, which may include T790M. 5. Patients must have untreated advanced Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy. --- L858R --- --- T790M ---



HPO Nodes


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