Non-small Cell Lung Cancer
Conditions
Keywords
Lung, non small cell, NSCLC, Irinotecan
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.
Interventions
DRUGIrinotecan
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
Sponsors
University of New Mexico Cancer Center
Lovelace Respiratory Research Institute
New Mexico Cancer Research Alliance
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
-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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response | 8 weeks | Change in tumor size will be measured by CT scan using RECIST criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Retrospectively Evaluate the Role of Tumor SULF2 Gene Methylation Status in Treatment Efficacy | 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. |
| Toxicity of Irinotecan Salvage Chemotherapy | 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 |
| 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. |
| Median Duration of Response | Up to 100 months | — |
| Median Overall Survival (OS) | 100 months | — |
| Progression Free Survival (PFS) | Up to 100 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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 | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease progression | 2 |
Baseline characteristics
| Characteristic | Irinotecan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 2 / 2 |
Outcome results
Primary
Tumor Response
Change in tumor size will be measured by CT scan using RECIST criteria.
Time frame: 8 weeks
Population: Both participants experienced an increase in tumor size between the time of the baseline CT scan and the first study CT scan. There will be no publication or further data analysis, as the study was terminated early due to low enrollment (2) and the original PI has left employment with the institution.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Irinotecan | Tumor Response | 2 Participants |
Secondary
Median Duration of Response
Time frame: Up to 100 months
Population: No data were collected for this outcome measure. There will be no publication or data analysis, as the study was terminated early due to low enrollment (2) and the original PI has left employment with the institution.
Secondary
Median Overall Survival (OS)
Time frame: 100 months
Population: No data were collected for this outcome measure. There will be no publication or data analysis, as the study was terminated early due to low enrollment (2) and the original PI has left employment with the institution.
Secondary
Progression Free Survival (PFS)
Time frame: Up to 100 months
Population: No data were collected for this outcome measure. There will be no publication or data analysis, as the study was terminated early due to low enrollment (2) and the original PI has left employment with the institution.
Secondary
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.
Time frame: 1 year
Population: No data was collected for this outcome measure. There will be no publication or data analysis, as the study was terminated early due to low enrollment (2) and the original PI has left employment with the institution.
Secondary
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.
Time frame: Up to 100 months
Population: No data were collected on this outcome measure. There will be no publication or data analysis, as the study was terminated early due to low enrollment (2) and the original PI has left employment with the institution.
Secondary
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
Time frame: 2 days preceding each cycle of therapy
Population: There will be no publication or data analysis, as the study was terminated early due to low enrollment (2) and the original PI has left employment with the institution.