Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
Conditions
Interventions
Intervention1: Lorlatinib and Posaconazole: Lorlatinib low dose 25mg with oral Posaconazole 300mg daily from Day 6 to Day 14
Control Intervention1: Lorlatinib: Lorlatinib 100 mg once daily from Day 1
Sponsors
ACTREC, TMC Tata Memorial Centre
Eligibility
Inclusion criteria
Inclusion criteria: Participants must meet all of the following: Age 18 years or older, male or female. Histologically or cytologically confirmed ALK positive advanced NSCLC. Indicated for lorlatinib therapy as per the treating oncologists discretion. ECOG performance status 2 or less. Adequate organ function at baseline: Hemoglobin 9.0 g per dL or higher ANC 1.5 x 10^9 per L or higher Platelets 100 x 10^9 per L or higher AST ALT 2.5 x ULN or less, or 5 x ULN or less if liver metastases Total bilirubin 1.5 x ULN or less Serum creatinine 1.5 x ULN or less or eGFR 60 mL per min per 1.73 m2 or higher Ability to comply with the inpatient stay and PK sampling schedule. Willing to provide signed written Informed Consent prior to any study specific procedures.
Exclusion criteria
Exclusion criteria: Concurrent use of strong CYP3A4 inducers or inhibitors other than study drug Posaconazole as per the study protocol. Concurrent use of any prohibited drugs as per Section 11. Known hypersensitivity to lorlatinib, posaconazole, or any excipients. Significant hepatic impairment Child Pugh B or C. History of CNS depression, severe psychiatric illness, or prior lorlatinib intolerance. Uncontrolled infection or comorbidities likely to interfere with participation. Patient consuming caffeine and alcohol concurrently. Pregnant or lactating women. Women of childbearing potential must use appropriate methods of contraception to avoid pregnancy. Unwillingness to provide informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AUC 0 to 24 ng h per mL: Total plasma exposure over 24 hours at steady state. Cmax ng per mL: Maximum plasma concentration at steady state. Ctrough ng per mL: Minimum plasma concentration prior to next dose. Pharmacokinetic equivalence will be concluded if the 90 percent confidence interval of the geometric mean ratio for AUC 0 to 24 and Cmax between Lorlatinib 25 mg plus Posaconazole 300 mg and Lorlatinib 100 mg monotherapy lies within the standard bioequivalence limits of 0.80 to 1.25.Timepoint: AUC 0 to 24 ng h per mL: Total plasma exposure over 24 hours at steady state. Cmax ng per mL: Maximum plasma concentration at steady state. Ctrough ng per mL: Minimum plasma concentration prior to next dose. Pharmacokinetic equivalence will be concluded if the 90 percent confidence interval of the geometric mean ratio for AUC 0 to 24 and Cmax between Lorlatinib 25 mg plus Posaconazole 300 mg and Lorlatinib 100 mg monotherapy lies within the standard bioequivalence limits of 0.80 to 1.25. | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of grade 2 or higher adverse events graded as per CTCAE version 5.0.Timepoint: Baseline, Day 5, Day 14, Day 15, and follow up at 7 days post discharge.;Change from baseline in biochemical parameters including liver function tests and lipid profile and central nervous system parameters specific for lorlatinib.Timepoint: Assessed at baseline, Day 5, Day 14, end of study Day 15, and at 7 day post discharge follow up.;Clinical evaluation of tolerability during combination therapy.Timepoint: Primarily assessed during Period 2, days 6 to 14.;Proportion of patients in the combination treatment period whose AUC 0 to 24 and Cmax fall outside plus or minus 2 standard deviations from the mean AUC 0 to 24 and Cmax measured during standard dose lorlatinib monotherapy.Timepoint: Pharmacokinetic deviation analysis will be performed using steady state data obtained on Day 5 and Day 14. | — |
Countries
India
Contacts
Public ContactDr Karunanidhan
Advanced Centre for Treatment, Research and Education in Cancer (ACTREC)
Outcome results
None listed