SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT04351555

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase III, Randomised, Controlled, Multi-center, 3-Arm Study of Neoadjuvant Osimertinib as Monotherapy or in Combination With Chemotherapy Versus Standard of Care Chemotherapy Alone for the Treatment of Patients With Epidermal Growth Factor Receptor Mutation Positive, Resectable Non-small Cell Lung Cancer

This is a Phase III, randomised, controlled, multi-centre, 3-arm study of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, versus SoC chemotherapy alone, for the treatment of patients with EGFRm (Ex19del and/or L858R), resectable Non-Small Cell Lung Cancer

NCT04351555 Non-Small Cell Lung Cancer
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

5 Interventions

Name: Osimertinib

Description: Oral
Type: Drug
Group Labels: 2

Osimertinib monotherapy Osimertinib with platinum-based chemotherapy

Name: Cisplatin

Description: Cisplatin(75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles.
Type: Drug
Group Labels: 2

Osimertinib with platinum-based chemotherapy Placebo with platinum-based chemotherapy

Name: Carboplatin

Description: Carboplatin(AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles
Type: Drug
Group Labels: 2

Osimertinib with platinum-based chemotherapy Placebo with platinum-based chemotherapy

Name: Placebo

Description: Oral
Type: Drug
Group Labels: 1

Placebo with platinum-based chemotherapy

Name: Pemetrexed

Description: Pemetrexed(500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles
Type: Drug
Group Labels: 2

Osimertinib with platinum-based chemotherapy Placebo with platinum-based chemotherapy


Primary Outcomes

Description: Defined as ≤10% residual cancer cells in the surgical specimen, as assessed per central pathology laboratory post-surgery

Measure: Major Pathological Response (MPR)

Time: From date of randomization to an average of 12 weeks after the first dose

Secondary Outcomes

Description: Defined as absence of any residual cancer cells in the surgical specimen assessed post-surgery

Measure: Pathological complete response (pCR)

Time: From date of randomization to an average of 12 weeks after the first dose

Description: An event is defined as documented disease progression that precludes surgery or requires non-protocol therapy; recurrence or a new lesion, local or distant (a new primary malignancy confirmed by pathology is not considered to be an EFS event.); death due to any cause

Measure: Event-free survival (EFS)

Time: Up to approximately 21 months after the last patient is randomized

Description: Patients will be followed up to approximately 5.5 years after they are randomized.

Measure: Overall Survival (OS)

Time: Up to approximately 5.5 years after the last patient is randomized

Description: DFS is defined as the time from the date of surgery until the first date of disease recurrence (local or distant) or date of death due to any cause, whichever occurs first. If there is residual disease after surgery (eg. positive margins), the DFS event is the date of surgery.

Measure: Disease free survival (DFS)

Time: From date of randomization up to approximately 15 months after date of resection

Description: Measured using lymph node staging

Measure: Downstaging

Time: From date of randomization to an average of 12 weeks after the first dose

Description: Assess disease-related symptoms, functioning, and global health status/quality-of-life in patients

Measure: Difference between treatment arms in change from baseline in EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items)

Time: From randomization to 24 weeks post-surgery

Measure: Concordance of EGFRm status between tumour tissue DNA and patient-matched plasma-derived ctDNA

Time: Baseline

Measure: Corcordance of EGFR mutation status between the local and central cobas EGFR mutation test results from baseline tumour samples

Time: Baseline

Measure: PK plasma concentrations of osimertinib

Time: From the pre-dose of Cycle 2 to post-dose of Cycle 3 (each cycle is 21 days)

Description: Assess lung cancer-associated symptoms and side effects from conventional chemotherapy and radiotherapy

Measure: Difference between treatment arms in change from baseline in EORTC QLQ-LC13 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items)

Time: From randomization to 24 weeks post-surgery

Other Outcomes

Description: The cure rate is defined as the percentage of people in this study who are still alive and disease free for a certain period of time after they finished the surgery. Here five-year landmark cure rate will be calculated in the same time as OS analysis.

Measure: Cure rate

Time: From the surgery until five years after surgery

Description: Other clinical variables include deaths, laboratory data, vital signs (pulse and BP), ECG, LVEF, ECOG performance status, and ophthalmologic assessment

Measure: Number of adverse events as assessed by CTCAE 5.0 and other clinical variables for safety and tolerability profile of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy prior to surgery compared with chemotherapy alone

Time: From the time of enrollment to either 28-days after the last dose of last study treatment for patients who do not undergo surgery, or 90-days post-surgery

Measure: MPR using plasma-derived circulating-free tumour DNA (ctDNA)

Time: From randomization to week 264 post-surgery

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 3 SNPs

SNPs


1 L858R

A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer This is a Phase III, randomised, controlled, multi-centre, 3-arm study of neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, versus SoC chemotherapy alone, for the treatment of patients with EGFRm (Ex19del and/or L858R), resectable Non-Small Cell Lung Cancer Major Pathological Response (MPR). --- L858R ---

- Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing - A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (ie, T790M, G719X, Exon20 insertions, S7681 and L861Q). --- L858R ---


2 L861Q

- Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing - A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (ie, T790M, G719X, Exon20 insertions, S7681 and L861Q). --- L858R --- --- T790M --- --- L861Q ---


3 T790M

- Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing - A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (ie, T790M, G719X, Exon20 insertions, S7681 and L861Q). --- L858R --- --- T790M ---



HPO Nodes


HPO: