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

Phase 1
Terminated
Conditions
Non-small Cell Lung Cancer
Interventions
Registration Number
NCT01607554
Lead Sponsor
New Mexico Cancer Care Alliance
Brief Summary

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

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
2
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:

  1. Total bilirubin less than or equal to 4.0 mg/dl, and
  2. 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
IrinotecanIrinotecanThe 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.
Primary Outcome Measures
NameTimeMethod
Tumor Response8 weeks

Change in tumor size will be measured by CT scan using RECIST criteria.

Secondary Outcome Measures
NameTimeMethod
Time to Progression (TTP)Up to 100 months

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.

Retrospectively Evaluate the Role of Tumor SULF2 Gene Methylation Status in Treatment Efficacy1 year

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.

Toxicity of Irinotecan Salvage Chemotherapy2 days preceding each cycle of therapy

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

Progression Free Survival (PFS)Up to 100 months
Median Duration of ResponseUp to 100 months
Median Overall Survival (OS)100 months

Trial Locations

Locations (3)

New Mexico Cancer Care Associates

🇺🇸

Santa Fe, New Mexico, United States

Hematology Oncology Associates

🇺🇸

Albuquerque, New Mexico, United States

University of New Mexico Cancer Center

🇺🇸

Albuquerque, New Mexico, United States

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