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Report for Clinical Trial NCT02157883

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase I, Open-label, Non-randomised Study to Assess the Effect of Itraconazole (a CYP3A4 Inhibitor) on the Pharmacokinetics of a Single Oral Dose of AZD9291 in Patients With EGFRm Positive NSCLC Whose Disease Has Progressed on an EGFR TKI

This is a 2 part study in patients with EGFRm+ non small cell lung cancer (NSCLC), whose disease has progressed on an EGFRm TKI, who are refractory or resistant to standard therapy. Part A will assess the effect of multiple oral doses of itraconazole on the single dose pharmacokinetic (PK) parameters of AZD9291. On completion of Part A, patients may continue to take AZD9291 tablets (Part B) following the collection of the 216 hour sample on Day 19 if they and the Investigator deem it appropriate, until such time as their disease progresses, the Investigator believes they are no longer deriving clinical benefit, or they stop taking AZD9291 for any other reason.

NCT02157883 Advanced Non Small Cell Lung Cancer Advanced (Inoperable) Non Small Cell Lung Cancer
MeSH: Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO: Neoplasm of the lung Non-small cell lung carcinoma

3 Interventions

Name: Pharmacokinetic sampling

Description: Blood samples taken pre and post dosing with AZD9291+/- itraconazole

Type: Procedure

AZD9291 alone, AZD9291+itraconozole

Name: AZD9291

Description: AZD9291 tablets: Part A 80mg od, days 1 and 10 only. Part B 80mg od for 12 months.

Type: Drug

AZD9291 alone, AZD9291+itraconozole

Name: Itraconazole

Description: Itraconazole tablets: 2x100mg bd, Part A days 6 to 19 only

Type: Drug

AZD9291 alone, AZD9291+itraconozole


Primary Outcomes

Description: Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration

Measure: Cmax of AZD9291

Time: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Description: Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to infinity

Measure: AUC of AZD9291

Time: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Secondary Outcomes

Description: Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to 120 hours

Measure: AUC(0-120) of AZD9291

Time: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Description: Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration curve from time zero to last quantifiable dose

Measure: AUC(0-t) of AZD9291

Time: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Description: Pharmacokinetics of AZD9291 by assessment of time to Cmax

Measure: Tmax of AZD9291

Time: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Description: Pharmacokinetics of AZD9291 by assessment of the terminal half-life

Measure: t1/2 of AZD9291

Time: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Description: Rate and extent of absorption of AZD9291 by assessment of apparent clearance following oral administration

Measure: CL/F of AZD9291

Time: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Description: Rate and extent of absorption of AZD9291 by assessment of the apprarent volume of distribution

Measure: Vz/F of AZD9291

Time: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Description: Pharmacokinetics of AZ5104 (metabolite to AZD9291) by assessment of maximum plasma AZ5104 concentration

Measure: Cmax of AZ5104

Time: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Description: Pharmacokinetics of AZ5104 (metabolite to AZD9291) by assessment of area under the plasma concentration time curve from zero to infinity

Measure: AUC of AZ5104

Time: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Description: Pharmacokinetics of AZ7550 (metabolite to AZD9291) by assessment of maximum plasma AZ7550 concentration

Measure: Cmax of AZ7550

Time: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Description: Pharmacokinetics of AZ7550 (metabolite to AZD9291) by assessment of area under the plasma concentration time curve from zero to infinity

Measure: AUC of AZ7550

Time: Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.

Purpose: Other

Single Group Assignment


There are 2 SNPs

SNPs


1 L858R

4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). 5. ECOG performance status 0-1 with no deterioration over the previous 2 weeks. --- L858R ---


2 L861Q

4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). 5. ECOG performance status 0-1 with no deterioration over the previous 2 weeks. --- L858R --- --- L861Q ---



HPO Nodes


HPO:
Neoplasm of the lung
Genes 61
REST GPC3 WT1 HPGD BRAF PIK3CA TP53 TRIM28 RB1 TRIP13 SLCO2A1 AKT1 CASP8 KRAS TSC1 POU6F2 EWSR1 PRKN LMNA NAB2 TERT TSC2 SLC22A18 BRCA2 PPP2R1B STAT6 STK11 MUC5B ERBB2 TSC2 MBTPS2 BAP1 TSC2 DICER1 PDGFRB PERP EGFR TSC1 DIS3L2 NOTCH3 KEAP1 DICER1 DICER1 WT1 TSC1 C11ORF95 IRF1 CYP2A6 WRN RELA WT1 PTEN SFTPC SFTPA2 ERCC6 TRPV3 TP53 H19 TRIM28 FASLG MAP3K8
Non-small cell lung carcinoma
Genes 3
TP53 TP53 BAP1