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Report for Clinical Trial NCT02616393

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 2, Multicenter Study of Tesevatinib in Subjects With Non-Small Cell Lung Cancer, EGFR Activating Mutation, Prior Treatment With a Tyrosine Kinase Inhibitor, and Brain Metastases or Leptomeningeal Metastases

A study to assess the activity of tesevatinib in subjects with NSCLC and activating EGFR mutations who have disease progression with Brain Metastases (BM) or Leptomeningeal Metastases (LM) or who heave either BM or LM at initial presentation.

NCT02616393 Non-Small Cell Lung Cancer Leptomeningeal Metastases Brain Metastases
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung Neoplasm Metastasis Neoplasms, Second Primary Brain Neoplasms Meningeal Carcinomatosis
HPO:Brain neoplasm Neoplasm of the lung Non-small cell lung carcinoma

1 Interventions

Name: Tesevatinib

Type: Drug
Group Labels: 3

Cohort A - Brain Metastases Cohort B - Leptomeningeal Metastases Cohort C - Brain Metastases at initial presentation


Primary Outcomes

Description: The primary objective is to evaluate the clinical activity of tesevatinib in subjects with non-small cell lung cancer (NSCLC), activating EGFR mutations, and BM as measured by RECIST 1.1 evaluated changes in BM size (Cohort A)

Measure: Clinical Activity of tesevatinib against BM using RECIST 1.1

Time: 12 months

Description: The primary objective is to evaluate the clinical activity of tesevatinib in subjects with NSCLC, activating EGFR mutations and/or LM as measured by improvement in CTCAE v4.03 symptoms and signs (Cohort B)

Measure: Clinical Activity of tesevatinib against LM using Symptom Resolution

Time: 12 months

Description: The primary objective is to evaluate the clinical activity of tesevatinib in subjects with non-small cell lung cancer (NSCLC), activating EGFR mutations, and BM at initial presentation as measured by RECIST 1.1 evaluated changes in BM size (Cohort C)

Measure: Clinical Activity of tesevatinib against BM at initial presentation using RECIST 1.1

Time: 12 months

Secondary Outcomes

Description: To evaluate changes in Quality of Life (QOL) in subjects receiving tesevatinib for BM using the EORTC QLQ-C30 and EORTC QLQ-BN20 Questionnaires

Measure: Quality of Life in Subjects Receiving tesevatinib for BM

Time: 12 months

Description: To evaluate changes in QOL in subjects receiving tesevatinib for LM using the EORTC QLQ-C30 and EORTC QLQ-BN20 Questionnaires

Measure: Quality of Life in Subjects Receiving tesevatinib for LM

Time: 12 months

Description: To evaluate changes in QOL in subjects receiving tesevatinib for BM at initial presentation using the EORTC QLQ-C30 and EORTC QLQ-BN20 Questionnaires

Measure: Quality of Life in Subjects Receiving tesevatinib for BM at initial presentation

Time: 12 months

Description: To determine the median progression-free survival (PFS) in Cohort A by assessing the median number of days from Cycle 1, Day 1 until disease progression or death

Measure: Median Progression-Free Survival in Cohort A

Time: 12 months

Description: To determine the rate of CNS non-progression at 3 and 6 months Cohort A by assessing the percentage of subjects in Cohort A without CNS disease progression 3 and 6 months after Cycle 1, Day 1

Measure: Rate of CNS Non-Progression in Cohort A

Time: 12 months

Description: To determine the rate of Non-CNS time to progression in Cohort A by assessing the median number of days in Cycle 1, Day 1 until non-CNS disease progression

Measure: Non-CNS Time to Progression in Cohort A

Time: 12 months

Description: To determine the rate of CNS TTPin Cohort A by assessing the median number of days in Cycle 1, Day 1 to disease progression

Measure: CNS TTP in Cohort A

Time: 12 months

Description: To determine the median progression-free survival (PFS) in Cohort B by assessing the median number of days from Cycle 1, Day 1 until disease progression or death

Measure: Median Progression-Free Survival in Cohort B

Time: 12 months

Description: To determine the rate of CNS non-progression at 3 and 6 months Cohort B by assessing the percentage of subjects in Cohort A without CNS disease progression 3 and 6 months after Cycle 1, Day 1

Measure: Rate of CNS Non-Progression in Cohort B

Time: 12 months

Description: To determine the rate of Non-CNS time to progression in Cohort B by assessing the median number of days in Cycle 1, Day 1 until non-CNS disease progression

Measure: Non-CNS Time to Progression in Cohort B

Time: 12 months

Description: To determine the rate of CNS TTP in Cohort B by assessing the median number of days in Cycle 1, Day 1 to disease progression

Measure: CNS TTP in Cohort B

Time: 12 months

Description: To determine the median overall survival (OS) in Cohort A by measuring the median number of days from Cycle 1, Day 1 until death

Measure: Median Overall Survival in Cohort A

Time: 12 months

Description: To determine the median OS in Cohort B by measuring the median number of days from Cycle 1, Day 1 until death

Measure: Median Overall Survival in Cohort B

Time: 12 months

Description: Evaluate the activity of tesevatinib in subjects with NSCLC as measured by decreases in NSCLC cells in the CSF using standard cytology as assessed by the percent change in the number of NSCLC cells in the CSF for each patient in cohort B from screening to Cycle 1, Day 14, from Day 14 to Cycle 3, Day 1, and from screening to Cycle 3, Day 1 (Cohort B)

Measure: Clinical Activity of tesevatinib against LM using Standard Cytology

Time: 12 months

Description: Evaluate the activity of tesevatinib in subjects with NSCLC as measured by changes in MRI findings consistent with leptomeningeal metastases (absent or present) for each patient in Cohort B from Cycle 1, Day 1 to Cycle 3, Day 1 and from Cycle 1, Day 1 to Cycle 5 Day 1 (Cohort B)

Measure: Clinical Activity of tesevatinib against LM using Improvement in MRI Findings

Time: 12 months

Description: To determine the median progression-free survival (PFS) in Cohort C by assessing the median number of days from Cycle 1, Day 1 until disease progression or death

Measure: Median Progression-Free Survival in Cohort C

Time: 12 months

Description: To determine the rate of CNS non-progression at 3 and 6 months Cohort C by assessing the percentage of subjects in Cohort C without CNS disease progression 3 and 6 months after Cycle 1, Day 1

Measure: Rate of CNS Non-Progression in Cohort C

Time: 12 months

Description: To determine the rate of Non-CNS time to progression in Cohort C by assessing the median number of days in Cycle 1, Day 1 until non-CNS disease progression

Measure: Non-CNS Time to Progression in Cohort C

Time: 12 months

Description: To determine the rate of CNS TTPin Cohort C by assessing the median number of days in Cycle 1, Day 1 to disease progression

Measure: CNS TTP in Cohort C

Time: 12 months

Description: To determine the median overall survival (OS) in Cohort C by measuring the median number of days from Cycle 1, Day 1 until death

Measure: Median Overall Survival in Cohort C

Time: 12 months

Description: To evaluate the concentration of tesevatinib in CSF versus plasma in Cohort B by obtaining PK analysis of plasma pre-dose on both Cycle 1 Day 14 and Cycle 3 Day 1, as well as obtaining PK samples of both plasma and CSF 4-8 hours after tesevatinib administration on Cycle 1 Day 14 and on Cycle 3 Day 1.

Measure: Pharmacokinetics in Cohort B: Concentration of tesevatinib in CSF versus plasma

Time: 12 Months

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There are 2 SNPs

SNPs


1 L858R

Subjects with a history of atrial arrhythmias should be discussed with the medical monitor - Has an active infectious process - Female subject who is pregnant or lactating - Known contraindication to MRI, such as cardiac pacemaker, shrapnel, or ocular foreign body - Has marked prolongation of QTc(F) interval at screening or baseline (QTc[F] interval > 470 msec) using the Fridericia method of correction for heart rate - Gastrointestinal (GI) condition that interferes with drug absorption - Non-malignant neurological disease that would interfere with evaluation of symptoms or signs of brain metastases Cohort B Inclusion Criteria: - History of NSCLC with EGFR mutation (either exon 19 deletion or L858R mutation) or, if previously treated, history of an activating EGFR mutation that has had a clinical response to erlotinib, afatinib, or gefitinib in the patient being enrolled). --- L858R ---


2 T790M

Patients may have received osimertinib (or other agents inhibiting the T790M EGFR mutation) as second line therapy. --- T790M ---



HPO Nodes


HPO: