Health Condition 1: J99- Respiratory disorders in diseasesclassified elsewhere
Conditions
Interventions
Intervention1: CYP3A4 Inhibition: Utility of Itraconazole at 200 mg twice daily to reduce dosage of osimertinib
Control Intervention1: EGFR inhibitor: Osimertinib in NSCLC
Sponsors
Department of pulmonary and critical care medicine
Eligibility
Inclusion criteria
Inclusion criteria: 1) pathologically confirmed advanced metastatic adenocarcinoma 2) No prior treatment with Itraconazole
Exclusion criteria
Exclusion criteria: 1. Previous receipt of EGFR-TKI. 2. Untreated HIV, HBV, HCV infections. 3. Previous or co-existing malignancy 4. Pregnant or lactating women 5. Any type of systemic anticancer therapy (chemotherapy or experimental drugs) within 2 weeks of starting treatment on protocol. 6. Any radiotherapy within 1 week of starting treatment on protocol. 7. Any major surgery within 4 weeks of starting treatment on protocol. 8. Any evidence of clinically significant interstitial lung disease 9. Known hypersensitivity to any component of Osimertinib or Itraconazole 10. Concomitant use of certain drugs due to serious or life-threatening interactions from CYP3A4 inhibition, such as antiarrhythmics, sedatives, sildenafil, antifungals etc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the pharmacokinetic profile of Osimertinib (80mg and 40mg) when co-administered with Itraconazole in EGFR-positive NSCLC patients.Timepoint: To determine the pharmacokinetic profile of Osimertinib (80mg and 40mg) when co-administered with Itraconazole in EGFR-positive NSCLC patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To assess the safety and tolerability (using predefined drug-limiting toxicities) of Osimertinib-Itraconazole combination in EGFR-positive NSCLC patients. 2. To investigate the relationship between plasma Osimertinib concentrations and clinical efficacy, including tumor response, disease control rates, and progression-free survival Timepoint: 1. Safety and tolerability: Incidence of all adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs). The incidence and severity of treatmentemergent adverse events (TEAEs) will be recorded according to CTCAE v5.0. 2. Cost-effectiveness: A cost-effectiveness analysis will be conducted to compare the different dosing regimens (80mg, 40mg, with and without Itraconazole). 3. Dose adjustments, including dose reduction, dose delay, or discontinuation due to drug-related toxicities. 4. Correlation between plasma Osimertinib concentrations and clinical outcomes (ORR, DCR, PFS). Evaluation of dose-response relationship for Osimertinib efficacy. | — |
Countries
India
Contacts
Public ContactDr Pawan Kumar Singh
Pandit B.D Sharma, PGIMS, Rohtak
Outcome results
None listed