SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01999985

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Phase I Trial Evaluating Safety and Tolerability of the Irreversible Epidermal Growth Factor Receptor Inhibitor Afatinib (BIBW 2992) in Combination With the SRC Kinase Inhibitor Dasatinib for Patients With Non-small Cell Lung Cancer (NSCLC)

The purpose of this study is to: - Find out if the study drugs Afatinib and Dasatinib can be safely given together to patients with lung cancer - Learn how these two drugs work in cancer cells when they are combined - Learn more about the side effects of these two drugs when combined - Find the highest doses of the study drugs Afatinib and Dasatinib that can be given safely without causing serious side effects

NCT01999985 Lung Cancer Non-small Cell Lung Cancer (NSCLC)
MeSH: Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO: Neoplasm of the lung Non-small cell lung carcinoma

4 Interventions

Name: Dasatinib - 1A

Description: 1A: Begins Day 8. Level 1 - 100 mg, Level 2 - 100 mg, Level 3 - 140 mg.

Type: Drug

Dose Escalation and Dose Expansion

Name: Afatinib - 1A

Description: 1A: Begins Day 1. Level 1 - 30 mg, Level 2 - 40 mg, Level 3 - 40 mg.

Type: Drug

Dose Escalation and Dose Expansion

Name: Dasatinib - 1B

Description: In Phase 1B, a mutationally selected 20 participants (total) will be treated at the recommended dose to confirm tolerability and evaluate for early response signal.

Type: Drug

Dose Escalation and Dose Expansion

Name: Afatinib - 1B

Description: In Phase 1B, a mutationally selected 20 participants (total) will be treated at the recommended dose to confirm tolerability and evaluate for early response signal.

Type: Drug

Dose Escalation and Dose Expansion


Primary Outcomes

Description: The MTD for this combined treatment will be defined as either: The highest dosage cohort in which six patients had been treated and there were less than two dose limiting toxicities (DLTs) or, Afatinib at the highest tolerated dose investigated (40 mg by mouth [PO] daily) plus dasatinib at the highest tolerated dose investigated (cohort 3, 140 mg PO daily).

Measure: Maximum Tolerated Dose (MTD) of Afatinib (BIBW 2992) in Combination With Dasatinib

Time: Up to 6 Months

Secondary Outcomes

Description: Estimates objective response rate (complete response [CR] and partial response [PR]) in participants with acquired EGFR resistance

Measure: Number of Participants With Objective Response

Time: Up to 6 Months

Description: Estimate the 6-month progression free survival (PFS) rate in participants with acquired EGFR resistance. Response Criteria for Phase 1B will follow RECIST v.1.1: Progressive Disease (PD) is defined as at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Measure: Median Progression Free Survival

Time: Up to 6 Months

Purpose: Treatment

Sequential Assignment


There is one SNP

SNPs


1 T790M

- Either or both of the following: Progression or recurrence of disease after receiving prior continuous gefitinib, afatinib, or erlotinib; A tumor known to harbor a de novo T790M mutation, which is known to confer EGFR TKI resistance. --- T790M ---



HPO Nodes


HPO:
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