Irinotecan for Previously Treated, Advanced, Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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Certain genetic factors can affect a patient's potential sensitivity to therapeutic drugs and other agents. There is a factor called ISG15 which might help doctors better identify patients with advanced non-small cell lung cancer (NSCLC) whose tumors may be more sensitive to the drug called Irinotecan. This factor is elevated in roughly 30% of NSCLC cases. Irinotecan is an agent that inhibits the enzyme called topoisomerase I that is involved in cell growth, and it has been FDA approved for 17 years for another type of cancer.

Detailed Description
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The goal of this trial is to demonstrate the potential clinical benefit of targeted irinotecan chemotherapy in NSCLC patients whose tumors display a specific phenotype that is associated with increased sensitivity to this drug, ISG15H.

Official Title
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A Pilot, Non-Randomized Phase II Protocol of Irinotecan for Patients With Previously Treated, Advanced, Non-Small Cell Lung Cancer With High ISG 15 Expression

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -INCLUSION: 18 years of age or older Have received prior chemotherapy for histologically proven advanced non-small cell lung cancer, up to 3 prior treatments Tumors display high ISG15 (ISG15H) at screening Life expectancy of at least 12 weeks ECOG/Zubrod performance status of 0-2 Provide informed consent permission to participate Adequate bone marrow function as follows: 1. Absolute neutrophil count of greater than or equal to 1,500 or cells/mm3, and 2) Platelet count greater than or equal to 100,000/mm3 and 3) Absence of a regular red blood cell transfusion requirement Adequate hepatic function with: Total bilirubin less than or equal to 4.0 mg/dl, and SGOT or SGPT less than or equal to four times ULN Adequate renal function as defined by: 1) Serum creatinine less than or equal to 1.5 x ULN Exclusion Criteria: Symptomatic brain metastases Pregnant women or nursing mothers Patients of child bearing potential must use adequate contraception. May not be receiving other concurrent chemotherapy or radiation therapy Severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections Previous hypersensitivity reaction to camptothecins

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Irinotecan<br>The starting dose of irinotecan for the study is 180 mg/m2, given intravenously every 14 days. Each 14 day period will constitute one cycle of treatment. | Drug: Irinotecan<br>* 180 mg/m2 Irinotecan intravenously over 60 minutes on day 1 of each cycle Pre-medication for irinotecan: palonosetron 0.25 mg and dexamethasone 8 - 16 mg, both administered intravenously. Atropine 0.25 - 0.5 mg subcutaneously or IV is at the discretion of the treating physician<br>* Other names: Camptosar; Campto;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response | Change in tumor size will be measured by CT scan using RECIST criteria. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression (TTP) | Time to progression will be measured from the time of first treatment until there is evidence of progressive disease or death, from the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 100 months. Death will be treated as a progression event. | Up to 100 months | 
| Retrospectively Evaluate the Role of Tumor SULF2 Gene Methylation Status in Treatment Efficacy | Patients who have a loss of SULF2 gene expression have a better outcome than those whose tumors express SULF2. High level of ISG15 expression in NSCLC may indicate a subgroup of tumors that may be more sensitive to the cytotoxic effects of irinotecan. In patients who consent to screening, 10 unstained slides of archived diagnostic tissue will be obtained from formalin-fixed, paraffin-embedded specimens and analyzed in the laboratories of our Lovelace Respiratory Research Institute co-investigators. | 1 year | 
| Toxicity of Irinotecan Salvage Chemotherapy | Use blood samples to measure possible 1) Neutropenia, 2) Thrombocytopenia, 3)Diarrhea; 4) Other measures of toxicity other than alopecia, anorexia, and asthenia as listed in the National Cancer Institute Common Toxicity Criteria v. 4.03 | 2 days preceding each cycle of therapy | 
| Progression Free Survival (PFS) |  | Up to 100 months | 
| Median Duration of Response |  | Up to 100 months | 
| Median Overall Survival (OS) |  | 100 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung, non small cell, NSCLC, Irinotecan