Lung Cancer
Conditions
Brief summary
The proposed study seeks to address a critical gap in the management of lorlatinib-induced metabolic derangements, particularly rapid weight gain, which can adversely affect treatment adherence, dosing and ultimately patient outcomes. In this study patients with non-small cell lung cancer (NSCLC) receiving lorlatinib treatment will receive tirzepatide, a dual GIP/GLP-1 receptor agonist with demonstrated efficacy in weight reduction and metabolic improvement. This study seeks to evaluate its potential to mitigate side effects while preserving the therapeutic efficacy of lorlatinib.
Interventions
DRUGTirzepatide
Participants will receive tirzepatide with weekly subcutaneous injections at 2.5 mg, following a structured dose escalation protocol over 20 weeks to reach the target dose of 15 mg per week or the maximum tolerated dose.
Sponsors
University of Chicago
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Receiving lorlatinib as first-line treatment for advanced NSCLC ALK-positive, already prescribed and administered by the patient's treating oncologist as standard of care at the time of study enrollment. This study does not initiate lorlatinib therapy or assign lorlatinib dosing; participants must already be receiving lorlatinib prior to enrollment
Exclusion criteria
* Known hypersensitivity to GLP-1 agonists. * Active, unstable psychiatric illness; current suicidal ideation * Severe organ dysfunction or systemic illness. * Anorexia nervosa * History of pancreatitis * Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 * Current use of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) or glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) \[GLP-1 RA/GIP\] co-agonist use within the last 90 days prior to screening * Current anti-obesity medication use (other than GLP-1 RA) or dipeptidyl peptidase-4 (DPP4) inhibitor use or use within the last 30 days prior to screening * Pregnant, breastfeeding or planning pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body weight changes | 1 year post treatment start | To assess the effect of tirzepatide, on change in body weight in patients taking lorlatinib. |
| Lipid changes | 1 year post treatment start | To assess the effect of tirzepatide on change in lipid profile High-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, triglycerides) at 52 weeks compared to baseline. |
| Change in Cmax | 1 year post treatment start | Determine if the peak concentration of Lorlatinib is significantly altered when co-administered with tirzepatide. |
| Change in Tmax | 1 year post treatment start | Assess if the time to peak concentration is delayed due to tirzepatide's effect on gastric emptying. |
| Bioavailability | 1 year post treatment start | Evaluate partial AUC to estimate the extent of drug absorption. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of metabolic side effects | 1 year from start of treatment | Number of Common Terminology Criteria for Adverse Events (CTCAE) Grade 1-3 metabolic side effects |
| Changes in body mass composition | 1 year from start of treatment | Changes in body mass will be measured using Bioelectrical Impedance Analysis (BIA). |
| Changes in waist circumference | 1 year from start of treatment | — |
| Changes in cardiometabolic markers | 1 year from start of treatment | The number of participants that experience a change in cardiometabolic markers will be reported. This includes changes in blood tests for any of the following: Hemoglobin A1c (HbA1c), insulin, glucose, Apolipoprotein B (ApoB), homocysteine, C-reactive protein (CRP), and lipoprotein(a) (Lp(a)) |
Countries
United States
Contacts
CONTACTClinical Trials Intake Intake
PRINCIPAL_INVESTIGATORMarina Garassino
University of Chicago
Outcome results
None listed