Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
Conditions
Interventions
Intervention1: Lorlatinib 50 mg alternate day: Lorlatinib 50 mg alternate Day with Itraconazole 100 mg once daily
Control Intervention1: Lorlatinib 25 mg alternate day: Lorlatinib 25 mg alternate Day
Sponsors
Department of Medical Oncology
Adi F Gazdar Fellowship Grant
Eligibility
Inclusion criteria
Inclusion criteria: 1.Histologically or cytologically confirmed locally advanced or metastatic non-squamous NSCLC with ALK positivity (ALK status determined by Ventana ALK (D5F3) CDx immunohistochemical assay) or demonstrated by Next Generation Sequencing or Polymerase Chain Reaction. 2.Measurable disease present according to RECIST v1.1 3.Adults more than 18 years of age with ECOG Performance status 0, 1 or 2. 4.Written informed consent obtained from subject or subject s legal representative and ability for subject to comply with the requirements of the study. 5.Has adequate organ function as defined below Not requiring dialysis. No acute hepatic failure due to any cause. SGOT, SGPT not more than 3 times ULN. No active congestive heart failure or arrhythmia. 6.Asymptomatic brain metastases. 7.Serum pregnancy test (for females of childbearing potential) negative at screening. 8.Prior chemotherapy (irrespective of number of cycles), treatment with ALK TKI will be included if 1) Lack of disease response was documented (radiographically) by an increase in tumour burden. 2) Associated toxicities have resolved to baseline . 3) ALK TKI was discontinued at least 2 weeks or 4 half-lives prior to enrolment, whichever is longer.
Exclusion criteria
Exclusion criteria: 1.All patients with co- mutation will be excluded. (Example Kras G12c, EGFR T790M etc) 2.Oncological emergencies such as symptomatic brain metastasis requiring local treatment, malignant cord compression, leptomeningeal disease will be excluded. 3.Active malignancy (i.e., progressing or requiring treatment change in the last 12 months) other than the disease being treated under study. 4.Pregnant, breastfeeding, or unwilling to practice birth control during participation. 5.Significant cardiovascular morbidity as below A.Prolonged corrected QT interval by Fridericia s (QTcF) more than 480 msec, clinically significant cardiac arrhythmia, or electrophysiologic disease. B.Congestive heart failure defined as New York Heart Association (NYHA) Class III/IV or hospitalization for congestive heart failure (any NYHA class) within previous 6 months (Can be included if medication are optimized) C.Hypertensive emergency- not controlled with optimal medical management. 6.Has severe hypersensitivity (more than Grade 3) to itraconazole. 7.Has a known psychiatric or substance abuse disorder that would interfere with the participant s ability to cooperate with the requirements of the study. 8.Has had an allogeneic tissue or solid organ transplant. 9.If the patient is on CYP3A4 inducers such as phenytoin, phenobarbitone, rifampicin which cannot be discontinued,alternate drug used for any reason. 10.Patient refusal to participate.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the objective response rates in patients on alternate day Lorlatinib with Itraconazole at 10 to 12 weeksTimepoint: To assess the objective response rates in patients on alternate day Lorlatinib with Itraconazole at 10 to 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| One year progression free survival (PFS) defined as the proportion of patients alive and progression-free at 12 monthsTimepoint: 12 months since initiation.;To evaluate the Cmax and AUC of Lorlatinib at reduced dose when co-administered with a strong CYP3A4 inhibitor (itraconazole).Timepoint: At 2 weeks or 12-18 weeks;Grade 3/4 adverse events as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.Timepoint: at every visit | — |
Countries
India
Contacts
Public ContactRuth Moses
CHRISTIAN MEDICAL COLLEGE AND HOSPITAL
Outcome results
None listed