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

• ClinicalTrials.gov Identifier: NCT01607554
• Recruitment Status: Terminated
• First Posted: May 30, 2012
• Results First Posted: April 13, 2018
• Last Update Posted: May 22, 2018
• Sponsor: New Mexico Cancer Care Alliance
• Collaborators: University of New Mexico Cancer Center; Lovelace Respiratory Research Institute
• Information provided by (Responsible Party): New Mexico Cancer Care Alliance

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: Irinotecan	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2012
• Actual Primary Completion Date: March 2013
• Actual Study Completion Date: March 2013

Arms and Interventions

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 Name: Camptosar; Campto

Outcome Measures

Primary Outcome Measures :

1. Tumor Response [ Time Frame: 8 weeks ]
   Change in tumor size will be measured by CT scan using RECIST criteria.

Secondary Outcome Measures :

1. Time to Progression (TTP) [ Time Frame: 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.
2. Retrospectively Evaluate the Role of Tumor SULF2 Gene Methylation Status in Treatment Efficacy [ Time Frame: 1 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.
3. Toxicity of Irinotecan Salvage Chemotherapy [ Time Frame: 2 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
4. Progression Free Survival (PFS) [ Time Frame: Up to 100 months ]
5. Median Duration of Response [ Time Frame: Up to 100 months ]
6. Median Overall Survival (OS) [ Time Frame: 100 months ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, New Mexico

Hematology Oncology Associates

Albuquerque, New Mexico, United States, 87106

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States, 87131

New Mexico Cancer Care Associates

Santa Fe, New Mexico, United States, 87505

Sponsors and Collaborators

New Mexico Cancer Care Alliance

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

More Information

Additional Information:

University of New Mexico Cancer Center, an NCI Designated Cancer Center 

New Mexico Cancer Care Alliance 

• Responsible Party: New Mexico Cancer Care Alliance
• ClinicalTrials.gov Identifier: NCT01607554
• Other Study ID Numbers: INST 1201; NCI-2012-01531 ( Registry Identifier: NCI CTRP )
• First Posted: May 30, 2012
• Results First Posted: April 13, 2018
• Last Update Posted: May 22, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by New Mexico Cancer Care Alliance:

Lung; non small cell; NSCLC; Irinotecan

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Irinotecan; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents