SNPMiner Trials (Home Page)
Report for Mutation H835L
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There is one clinical trial.
Clinical Trials
1 A Phase I/Ib Study of Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer
This is a phase I/Ib, open-label, single-center, single-arm study of alisertib and osimertinib for patients with stage IV EGFR-mutated lung cancer, incorporating both a dose escalation and dose-expansion phase
NCT04085315 Lung Cancer Metastatic EGFR Gene Mutation Drug: Osimertinib Drug: Alisertib MeSH:Lung Neoplasms
HPO:Neoplasm of the lung
2. Male or female patients ≥18 years of age 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Appendix 1). 4. Documented activating EGFR mutation (Exon 19 deletion, Exon 19 insertion, E709K, G719X, S768I, V769L, T790M, L833F, L833V, V834L, H835L, L858R, A859S, K860I, L861Q, A871E, V843I, or H870R) on tumor sample or cell-free DNA sample performed inClinical Laboratory Improvement Amendments (CLIA)-approved laboratory. 5. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. --- E709K --- --- S768I --- --- V769L --- --- T790M --- --- L833F --- --- L833V --- --- V834L --- --- H835L ---
Primary Outcomes
Description: ≤1 out of 6 at highest dose level below the maximal administered dose. If 0 of these 3 additional participants experience a dose limiting toxicity (DLT) (1 of 6), proceed to the next dose level. If 1 or more of the 3 additional participants experience DLT (2 of 6), then dose escalation is stopped, and this dose is declared the maximal administered dose (highest dose administered). Three (3) additional participants will be entered at the next lowest dose level if only 3 participants were treated previously at that dose.
Measure: Maximum Tolerated Dose (MTD) Time: First 28 days of study treatmentSecondary Outcomes
Description: defined as the best overall response recorded from the start of the treatment until disease progression from the start of treatment. The frequency and percentages of patients with a best overall response rate of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be determined based on RECIST 1.1 criteria. We will compute a 95% confidence interval using a binomial distribution.
Measure: Overall Response Rate (ORR) Time: Up to 2 yearsDescription: The DR for CR and PR will be measured from the date that the best response if first recorded until the date that PD is documented over the period of 2 years. For patients who continue treatment post-progression, the date of PD documentation will be used for analysis. The DR will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum)
Measure: Duration of Response (DR) Time: Up to 2 yearsDescription: The depth of response will be assessed by RECIST 1.1 criteria. The DOR will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum).
Measure: Depth of response (DOR) Time: Up to 2 yearsDescription: Defined as the percentage of patients who have achieved CR, PR, or SD for at least 12 weeks. The DCR will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum).
Measure: Disease Control Rate (DCR) Time: Up to 2 yearsDescription: PFS will be calculated as 1+ the number of days from the first dose of alisertib to documented radiographic progression or death due to any cause over a period of 2 years. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis. The Kaplan-Meier analysis will be used to calculate the mean PFS with 95% confidence interval.
Measure: Progression Free Survival (PFS) Time: Up to 2 yearsDescription: OS will be calculated as 1+ the number of days from the first dose of alisertib to death due to any cause over a period of 2 years. The Kaplan-Meier analysis will be used to calculate the mean OS with 95% confidence interval.
Measure: Overall Survival (OS) Time: Up to 2 yearsDescription: Defined as the percentage of patients who have achieved CR, PR, or SD in the CNS for at least 12 weeks. The CNS disease control rate will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum).
Measure: Central Nervous System (CNS) disease control rate Time: Up to 2 yearsDescription: Pre-treatment tumor biopsy formalin-fixed paraffin-embedded (FFPE) samples will be stained for TPX2 expression by IHC. TPX2 IHC staining will be scored using the following scale: 0, 0-10% of tissue stained positive; 1, 10-20% stained positive; 2, 20-40% stained positive; 3, 40-70% stained positive; and 4, > 70% positive cells. The sum of staining score index (intensity + extent) will be designated as follows: 0-2, negative expression; 3-4, strong expression. The IHC score will be generated from three different areas of the slides and an average score will be calculated for each sample. We will determine whether there is a difference in TPX2 staining between responders and non-responders to alisertib + osimertinib treatment by the Fisher's exact test.
Measure: Intratumoral TPX2 expression by Immunohistochemistry (IHC) Time: From pretreatment biopsy to time of response, up to 2 yearsDescription: Plasma will be collected to measure the drug concentrations at the indicated time points and area under curve (AUC) 0-24 hours. The area under the curve (AUC) is the definite integral in a plot of drug concentration in blood plasma vs. time
Measure: Area Under Curve (AUC) Time: 1, 2, 3, 4, 6, 8, and 24 hours post-dose, up to 2 daysDescription: Plasma will be collected to measure the drug concentrations at the indicated time points and Cmax will be calculated. It is a standard measurement in pharmacokinetics
Measure: Maximum (or peak) serum concentration (Cmax) Time: 1, 2, 3, 4, 6, 8, and 24 hours post-dose, up to 2 daysDescription: Plasma will be collected to measure the drug concentrations at the indicated time points and Tmax will be calculated. It is a standard measurement in pharmacokinetics
Measure: Amount of time (maximum) drug concentration in serum (Tmax) Time: 1, 2, 3, 4, 6, 8, and 24 hours post-dose, up to 2 days