SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03410043

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Randomized Phase II Trial of Local Consolidation Therapy (LCT) After Osimertinib for Patients With EGFR Mutant Metastatic Non-Small Cell Lung Cancer (NSCLC)

This phase II trial studies how well osimertinib, surgery, and radiation therapy work in treating patients with stage IIIB or IV non-small cell lung cancer with EGFR mutations. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving osimertinib, surgery, and radiation therapy may work better at treating non-small cell lung cancer with EGFR mutations.

NCT03410043 EGFR Exon 19 Deletion Mutation EGFR NP_005219.2:p.L858R EGFR NP_005219.2:p.T790M Lung Non-Small Cell Carcinoma Recurrent Lung Non-Small Cell Carcinoma Stage IIIB Lung Cancer AJCC v8 Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8
MeSH: Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO: Carcinoma Neoplasm of the lung Non-small cell lung carcinoma

3 Interventions

Name: Osimertinib

Description: Given PO

Type: Drug

Group I (LCT) Group II (no LCT)

Name: Radiation Therapy

Description: Undergo radiation therapy

Type: Radiation

Group I (LCT)

Name: Therapeutic Conventional Surgery

Description: Undergo surgery

Type: Procedure

Group I (LCT)


Primary Outcomes

Description: Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between treatment groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis and to estimate hazard ratios.

Measure: Progression free survival (PFS)

Time: From the start date of osimertinib assessed up to 4 years

Secondary Outcomes

Description: Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between treatment groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis and to estimate hazard ratios.

Measure: Overall survival

Time: From the treatment start date assessed up to 4 years

Description: Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between treatment groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis and to estimate hazard ratios.

Measure: Time to progression of target lesions

Time: Up to 4 years

Description: Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between treatment groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis and to estimate hazard ratios.

Measure: Time to appearance of new metastases

Time: Up to 4 years

Description: Will be estimated using Kaplan-Meier method. The stratified log-rank test will be performed to test the difference in time-to-event distributions between treatment groups. Stratified Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis and to estimate hazard ratios.

Measure: PFS in oligometastatic subgroup

Time: Up to 4 years

Description: Toxicity data related to the treatments will be summarized by frequency tables. The association between the types and severity of toxicity and the treatment groups will be evaluated.

Measure: Incidence of adverse events

Time: Up to 30 days post treatment

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 3 SNPs

SNPs


1 L8585R

To determine whether osimertinib plus LCT improves progression-free survival compared with osimertinib alone in TKI naive EGFR (L8585R/exon 19 deletion) mutant metastatic NSCLC. --- L8585R ---


2 L858R

The association between the types and severity of toxicity and the treatment groups will be evaluated.. Inclusion Criteria: - Histologically or cytologically confirmed non-small cell lung cancer - Stage IIIB/IV or recurrent non-small cell lung cancer which is not amenable to curative intent therapy - Patients must have one of the following: - NSCLC which harbors EGFR exon 19 deletion or L858R mutation. --- L858R ---

In addition, these lesions will be counted towards the total number of metastases, and will also be counted as target lesions Inclusion Criteria: - Histologically or cytologically confirmed non-small cell lung cancer - Stage IIIB/IV or recurrent non-small cell lung cancer which is not amenable to curative intent therapy - Patients must have one of the following: - NSCLC which harbors EGFR exon 19 deletion or L858R mutation. --- L858R ---


3 T790M

This subset of patients must be TKI naive; OR - NSCLC which harbors an EGFR T790M mutation that was acquired following progression on erlotinib, gefitinib or afatinib. --- T790M ---

In addition, these lesions will be counted towards the total number of metastases, and will also be counted as target lesions EGFR Exon 19 Deletion Mutation EGFR NP_005219.2:p.L858R EGFR NP_005219.2:p.T790M Lung Non-Small Cell Carcinoma Recurrent Lung Non-Small Cell Carcinoma Stage IIIB Lung Cancer AJCC v8 Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung PRIMARY OBJECTIVES: I. To determine whether, in patients with tyrosine kinase inhibitor (TKI) naive or TKI resistant (acquired T790M) metastatic EGFR mutant non-small cell lung cancer (NSCLC) who do not progress after 6-12 weeks of induction osimertinib, local consolidative therapy (LCT; radiotherapy +/- surgical resection) followed by osimertinib prolongs progression-free survival (PFS) compared with osimertinib alone. --- T790M ---

To determine whether osimertinib plus LCT improves progression-free survival compared with osimertinib alone in TKI resistant (acquired T790M) EGFR mutant NSCLC. --- T790M ---



HPO Nodes


HPO:
Carcinoma
Genes 11
PTEN CDKN1B APC MLH1 MSH2 FGFR3 KIT DKC1 RSPO1 STK11 NLRP1
Neoplasm of the lung
Genes 43
WT1 KRAS SLC22A18 STK11 IRF1 AKT1 C11ORF95 PRKN PPP2R1B ERBB2 TRPV3 TSC1 POU6F2 TSC2 EWSR1 RELA KEAP1 REST DIS3L2 SFTPA2 GPC3 MBTPS2 LMNA PTEN BRAF BRCA2 EGFR RB1 TRIP13 PDGFRB TERT SFTPC PIK3CA TRIM28 DICER1 MAP3K8 HPGD SLCO2A1 H19 TP53 NOTCH3 BAP1 WRN
Non-small cell lung carcinoma
Genes 2
TP53 BAP1