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

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

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.

Study Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Irinotecan

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87106
      • Hematology Oncology Associates
    • Santa Fe, New Mexico, United States, 87505
      • New Mexico Cancer Care Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Irinotecan; 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; 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; Other Names: Camptosar; Campto

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: New Mexico Cancer Care Alliance
• Collaborators: University of New Mexico Cancer Center; Lovelace Respiratory Research Institute
• Investigators: Principal Investigator: Martin J Edelman, MD, UNM Cancer Center; Principal Investigator: Mathewos Tessema, PhD, Lovelace Respiratory Research Institute

Publications and helpful links

Helpful Links

• New Mexico Cancer Care Alliance
• University of New Mexico Cancer Center, an NCI Designated Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: May 9, 2012
• First Submitted That Met QC Criteria: May 24, 2012
• First Posted (Estimate): May 30, 2012

Study Record Updates

• Last Update Posted (Actual): May 22, 2018
• Last Update Submitted That Met QC Criteria: April 23, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: NSCLC; Lung; Irinotecan; non small cell
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: INST 1201; NCI-2012-01531 (Registry Identifier: NCI CTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO