SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03769103

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Open Label, Multicenter, Phase II Study of Patients With Treatment Naïve Metastatic Epidermal Growth Factor Receptor (EGFR) Mutation-Positive Non-Small Cell Lung Cancer (NSCLC) With Brain Metastases Randomized to Stereotactic Radiosurgery (SRS) and Osimertinib or Osimertinib Alone

This open-label, multicenter, randomized phase II study will evaluate the usage of osimertinib alone for brain metastases compared to SRS and osimertinib in patients with newly diagnosed, treatment naiive EGFR positive lung cancer.

NCT03769103 Lung Cancer Non-small Cell Stage IV Brain Metastases
MeSH: Lung Neoplasms Neoplasm Metastasis Brain Neoplasms Carcinoma, Non-Small-Cell Lung
HPO: Brain neoplasm Neoplasm of the lung Non-small cell lung carcinoma

2 Interventions

Name: Osimertinib

Description: Daily oral osimertinib

Type: Drug

SRS + Osimertinib Osimertinib alone

Name: Stereotactic radiotherapy

Description: 1-5 fractions of stereotactic radiotherapy

Type: Radiation

SRS + Osimertinib


Primary Outcomes

Description: Absence of progressive brain metastases according to the Response Assessment in Neuro-Oncology Brain Metastasis (RANO-BM criteria)

Measure: Intracranial progression free survival

Time: 1 year

Secondary Outcomes

Description: partial or complete response to therapy based on RANO-BM criteria

Measure: Intracranial overall response rate

Time: 2 years

Description: time from randomization to WBRT

Measure: Time to whole brain radiotherapy (WBRT)

Time: 2 years

Description: time from randomization to SRS (not including initial SRS in the SRS + osimertinib treatment arm)

Measure: Time to stereotactic radiosurgery (SRS)

Time: 2 years

Description: according to institutional standards based on radiologic findings with or without pathologic confirmation and multidisciplinary review when required

Measure: Rate of radionecrosis

Time: 2 years

Description: defined as time from randomization to death by any cause

Measure: Overall survival

Time: 2 years

Description: time from randomization to progression of extracranial metastases or development of new sites of disease per RECIST 1.1

Measure: Time to distant progression

Time: 2 years

Description: Assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30. Subscales for: general presence of symptoms in patients with cancer question 1-28 (1=Not at all; 4=very much); overall health/quality of life question 29-30 (1=very poor; 7=excellent) & EORTC-QLQ Brain Neoplasm (BN)20: Subscales for presence of symptoms in patients with brain tumours question 31-50 (1=Not at all; 4=very much)

Measure: Quality of life

Time: 2 years

Description: Assessed by Montreal Cognitive Assessment. Total score:30. 1=poor function; 30=good function

Measure: Neurocognitive function

Time: 2 years

Description: Osimertinib dose (40mg or 80mg) for x number of days (max=730 days)

Measure: Exposure to osimertinib

Time: 2 years

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 L858R

Inclusion Criteria: - Able to provide written informed consent by patient or legally acceptable representative - Meets the criteria in the approved regulatory indication for first line treatment with osimertinib and agree to the restrictions, monitoring, and dose-adjustment criteria stipulated in the associated product label - Epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations (either alone or in combination with other EGFR mutations) - No prior systemic therapy except neoadjuvant, adjuvant or concurrent chemotherapy given greater than 3 months prior to enrollment on study - Asymptomatic or minimally symptomatic brain metastases (ie. --- L858R ---

Headache, nausea, or seizure responsive to dexamethasone/analgesic/antiepileptic on stable doses of medications for a minimum of 3 days) - Brain metastases must meet the following criteria on a diagnostic MRI: at least one lesion can be classified as measurable disease per RANO-BM, ≤ 10 brain or brainstem metastases, ≤ 30 mm and brainstem metastases must be ≤ 10 mm, metastases > 5 mm from the optic nerve or chiasm - ECOG performance status 0-2 - Life expectancy > 6 months - Willing to abstain from sexual activity or willing to use double-barrier method during sexual intercourse Exclusion Criteria: - Previous treatment with osimertinib, or any other EGFR TKI - Patient with symptomatic brain metastases causing any neurologic deficit (not including headache, nausea, or medically controlled seizure) - Multiple sclerosis - Pacemaker or MRI-incompatible metal in the body - Allergy to gadolinium MRI contrast - Brain metastasis requiring surgery for decompression - Leptomeningeal disease - Previous cranial RT, or surgery for brain metastases - Uncontrolled systemic lupus erythematosis, scleroderma or other connective tissue disorders considered a contraindication for radiotherapy - Active cancer from another anatomical site within 5 years (non-melanomatous skin and cervical cancers permitted) - Any medical or non-medical issue that would render patient unable to reliably complete regular QOL and neurocognitive assessments - Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements - Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater - Patients with symptomatic CNS metastases who are neurologically unstable - Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4 - Patients taking any drugs that are known to prolong QT interval that can't be withdrawn prior to Osimertinib - Pregnant or breastfeeding Inclusion Criteria: - Able to provide written informed consent by patient or legally acceptable representative - Meets the criteria in the approved regulatory indication for first line treatment with osimertinib and agree to the restrictions, monitoring, and dose-adjustment criteria stipulated in the associated product label - Epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations (either alone or in combination with other EGFR mutations) - No prior systemic therapy except neoadjuvant, adjuvant or concurrent chemotherapy given greater than 3 months prior to enrollment on study - Asymptomatic or minimally symptomatic brain metastases (ie. --- 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