SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02338011

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Gefitinib Alone or With Concomitant Whole Brain Radiotherapy for Patients Harboring an EGFR Mutation With Multiple Brain Metastases From Non-Small-cell Lung Cancer: a Phase II/III Randomized Controlled Trial

1. Compare the effect and safety of gefitinib alone with gefitinib plus concomitant WBRT(whole-brain radiotherapy ) in treatment of NSCLC patients harboring an EGFR mutation with multiple BM. 2. Verify the failure pattern of NSCLC patients harboring an EGFR mutation with multiple BM. 3. Explore the rescuable therapy after progression of disease.

NCT02338011 Non-Small Cell Lung Cancer Brain Metastases EGFR Gene Mutation
MeSH: Lung Neoplasms Carcinoma, Non-Small-Cell Lung Neoplasm Metastasis Brain Neoplasms
HPO: Brain neoplasm Neoplasm of the lung Non-small cell lung carcinoma

2 Interventions

Name: Gefitinib

Description: Gefitinib was given 250mg per day. Dose reduction was allowed for intolerable adverse effects such as rash(grade 4)、diarrhea(grade 3-4) or non hematological toxicity(grade 3-4) from 250mg per day to 250mg every other day then to 250mg every three days if needed.

Type: Drug

Gefitinib alone Gefitinib concurrent WBRT

Name: WBRT

Description: WBRT was delivered in 3.0 Gy fractions once per day 5 days per week to a total dose of 30Gy (10 fractions).

Type: Radiation

Gefitinib concurrent WBRT


Primary Outcomes

Description: Compare the progression free survival(PFS) and safety in two arms,including intracranial PFS、extracranial PFS and overall PFS.

Measure: Time to progression

Time: 12-14 months

Secondary Outcomes

Measure: Overall survival

Time: 3 years

Description: intracranial or extracranial site

Measure: Disease Progression Classification

Time: 3 years

Description: measured by ECGO(Eastern Cooperative Oncology Group) PS (Performance Status)

Measure: Health-related quality of life

Time: 3 years

Description: measured by scale of MMSE( Mini Mental Status Examination)

Measure: Mental Status

Time: 3 years

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 L858R

Inclusion Criteria: - years of age or older - ECOG score ≤ 2 - Recursive Partitioning Analysis(RPA) Class I-II; - The pathological diagnosis of primary non-small cell lung cancer and detection of pulmonary primary ARMs; - Sequencing EGFR mutation(primary lesion or metastases,exon 19 deletions or exon 21 L858R (EGFR mutation in exon 21, L858R point mutation) mutations; - Enhanced MRI showed brain metastases ≥ 4; - 1 or 2 line treatment revealed failure; - No use of EGFR-TKIs(Tyrosine kinase inhibitors) previously; - No treatment for BM previously,including WBRT, SRS, surgery or experimental therapy; - Expected survival period over 3 months; - Two weeks before randomization, organs function in patients with meet the following criteria: - bone marrow:HB(hemoglobin) ≥ 90g/L, neutrophil≥ 1.5 × 109/L and platelet ≥ 100 × 109/L; - liver function:total bilirubin ≤ 1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal; - renal function:more than 1.5 times the upper limit of normal serum creatinine or creatinine clearance rate ≥ 60 ml/min; - Urine dipstick testing the proteinuria < 1+; if the urine dipstick test value, 1+, is 24 hours total urine protein must < 500mg; - blood glucose:normal range,DM(diabetes mellitus) patients are under treatment and have a stable state; - Can understand and consent Exclusion Criteria: - Patients have been treated with brain radiation or surgery of BM; - Prior of EGFR-TKIs; - Mixed with small cell lung cancer patients with components; - Wild-type of EGFR; - Unable to tolerate MRI scanning; - Post 2 line treated patients; - Brain meninges metastases or incorporate with brain meninges metastases; - 5 years before other cancers except NSCLC treatment in patients with the start of the study (except for simple operation resection and there are at least 5 consecutive years disease free survival, has been cured of cervical carcinoma in situ, has cured the base cell cancer and bladder epithelial tumor); - Before entering the group 4 weeks received any other investigational drugs; - Incorporate with local symptoms(hemiplegic paralysis, anepia, nystagmus, ataxia.et); --- L858R ---

Inclusion Criteria: - years of age or older - ECOG score ≤ 2 - Recursive Partitioning Analysis(RPA) Class I-II; - The pathological diagnosis of primary non-small cell lung cancer and detection of pulmonary primary ARMs; - Sequencing EGFR mutation(primary lesion or metastases,exon 19 deletions or exon 21 L858R (EGFR mutation in exon 21, L858R point mutation) mutations; - Enhanced MRI showed brain metastases ≥ 4; - 1 or 2 line treatment revealed failure; - No use of EGFR-TKIs(Tyrosine kinase inhibitors) previously; - No treatment for BM previously,including WBRT, SRS, surgery or experimental therapy; - Expected survival period over 3 months; - Two weeks before randomization, organs function in patients with meet the following criteria: - bone marrow:HB(hemoglobin) ≥ 90g/L, neutrophil≥ 1.5 × 109/L and platelet ≥ 100 × 109/L; - liver function:total bilirubin ≤ 1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal; - renal function:more than 1.5 times the upper limit of normal serum creatinine or creatinine clearance rate ≥ 60 ml/min; - Urine dipstick testing the proteinuria < 1+; if the urine dipstick test value, 1+, is 24 hours total urine protein must < 500mg; - blood glucose:normal range,DM(diabetes mellitus) patients are under treatment and have a stable state; - Can understand and consent Exclusion Criteria: - Patients have been treated with brain radiation or surgery of BM; - Prior of EGFR-TKIs; - Mixed with small cell lung cancer patients with components; - Wild-type of EGFR; - Unable to tolerate MRI scanning; - Post 2 line treated patients; - Brain meninges metastases or incorporate with brain meninges metastases; - 5 years before other cancers except NSCLC treatment in patients with the start of the study (except for simple operation resection and there are at least 5 consecutive years disease free survival, has been cured of cervical carcinoma in situ, has cured the base cell cancer and bladder epithelial tumor); - Before entering the group 4 weeks received any other investigational drugs; - Incorporate with local symptoms(hemiplegic paralysis, anepia, nystagmus, ataxia.et); --- L858R --- --- L858R ---



HPO Nodes


HPO:
Brain neoplasm
Genes 7
POLD1 POLE RELA APC RB1 FLI1 C11ORF95
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