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Gene Expression Levels in Predicting Treatment Response in Patients With Stage IV Non-small Cell Lung Cancer

Primary Purpose

Recurrent Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
docetaxel
pemetrexed disodium
gemcitabine hydrochloride
laboratory biomarker analysis
Sponsored by
Barbara Ann Karmanos Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with advanced stage NSCLC who are candidates for single or multi-agent first-line therapy.
  • Second-line or higher therapy for any patients with NSCLC with performance status (PS) 0-2
  • Maintenance therapy for patients after completion of four cycles of dual-agent platinum-based chemotherapy
  • Stage IV, histologically or cytologically confirmed NSCLC; confirmation may be obtained with the first protocol-specified tumor biopsy
  • White blood cell count > 3000/mm^3
  • Platelet count > 100,000/mm^3
  • Hemoglobin > 9.0 g/dl
  • A tumor lesion that can be safely biopsied as judged by the treating oncologist and physician performing the procedure and has not been radiated
  • At least one unidimensionally measurable tumor lesion >= 1 cm in longest diameter using spiral CT (>= 2 cm in longest diameter by any other technique) that has not been radiated and is not located in a bone
  • Performance status 0-2 by Eastern Cooperative Oncology Group criteria
  • Life expectancy of >= 3 months
  • Able to understand and sign the informed consent document

Exclusion Criteria:

  • Therapy that does not include cisplatin, carboplatin, gemcitabine, and/or pemetrexed
  • Concomitant medical or psychiatric illness that is likely to interfere with a reasonably safe execution of the treatment plan
  • Concomitant malignancy other than NSCLC that requires active therapy; prior malignancies are allowed as long as the disease is controlled and does not require ongoing therapy of any kind; prior therapy must have concluded at least 1 year before treatment initiation on this protocol; exceptions are non-melanoma skin cancer, prostate cancer and prostatic intraepithelial neoplasia (PIN) treated with local intervention and deemed cured, cervical cancer and carcinoma in situ (CIS) treated with local intervention and deemed cured, and laryngeal cancer and CIS treated with local intervention and deemed cured
  • Carcinomatous meningitis
  • Uncontrolled central nervous system (CNS) disease
  • The time interval between CNS radiation, whole brain radiation, spinal cord radiation, or radiosurgery, and initiation of protocol specified chemotherapy must be at least 1 week
  • Malignant pleural, pericardial, or peritoneal effusion if it is the only site of disease activity; i.e., if no other measurable tumor lesions exist
  • Coagulopathy or anticoagulation therapy that cannot be safely corrected or interrupted for tumor biopsy
  • Significant hepatic dysfunction, renal dysfunction, or metabolic derangement that precludes full-dose chemotherapy at the specified starting doses
  • Concomitant treatment with chemotherapeutic agents for diseases other than malignancy
  • Pregnancy or lactation

Sites / Locations

  • Barbara Ann Karmanos Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemotherapy regimen)

Arm Description

Patients receive 1 of 4 chemotherapy regimens at the discretion of the primary oncologist following institutional guidelines, including cisplatin, carboplatin, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After course 2, patients may continue treatment off-study at the discretion of the treating physician.

Outcomes

Primary Outcome Measures

Baseline Marker Measurement
A univariable regression of continuous disease response on baseline marker value will be performed. A multivariable regression model adjusted for clinical covariates will be evaluated as well. Expression levels of RRM1, TS, BRCA1, and other molecules and disease response after course 2 will be log-transformed.

Secondary Outcome Measures

Change in Biomarker Expression Levels
Evaluated using Pearson correlation. If data are not normally distributed after log transformation, a non-parametric method (e.g., Spearman correlation) will be used.
Overall Survival (OS)
Since, the study was canceled due to slow accrual, no biomarkers were measured; therefore, no analysis with biomarkers. Only the OS will be calculated.
Progression-free Survival (PFS)
Each biomarker evaluated using its expression level (continuous variable) and dichotomous form (based on a median cutoff). A univariable Cox regression model will be used to assess the relationship of expression levels of each biomarker to PFS. In addition, for the dichotomous variables, the sample will be divided into those above and below the median for each biomarker. PFS probabilities for each group will be estimated using the Kaplan-Meier method, with standard errors based on Greenwood's formula. Log rank tests will be used to determine the level of significance between survival curves. Since, the study was canceled due to slow accrual, no biomarkers were measured; therefore, no analysis with biomarkers. Only the PFS will be calculated.
Expression Levels of Biomarkers and Other Molecules
To assess the relationship between expression levels of RRM1, TS, BRCA1, and other molecules and demographic and disease variables, the Wilcoxon rank sum test or Kruskal-Wallis test for dichotomous or polychotomous categorical variables (such as sex, and histology) and the Spearman correlation coefficient for continuous ordinal variables (such as age or stage) will be used.

Full Information

First Posted
May 20, 2014
Last Updated
September 3, 2020
Sponsor
Barbara Ann Karmanos Cancer Institute
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02145078
Brief Title
Gene Expression Levels in Predicting Treatment Response in Patients With Stage IV Non-small Cell Lung Cancer
Official Title
A Pilot Trial of Platinum, Gemcitabine, or Pemetrexed Single- or Multi-Agent Therapy With Serial Tumor Specimen Collection in Patients With Advanced Non-Small-Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual.
Study Start Date
June 2014 (undefined)
Primary Completion Date
June 18, 2015 (Actual)
Study Completion Date
March 7, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Barbara Ann Karmanos Cancer Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This pilot clinical trial studies whether the levels of certain genes in the tissue and blood are related to how well patients with stage IV non-small cell lung cancer respond to chemotherapy. Genes may affect how sensitive or resistant tumors are to chemotherapy. Studying the levels of genes related to tumor response before and after chemotherapy may help doctors learn whether they can predict how well patients will respond to treatment.
Detailed Description
PRIMARY OBJECTIVES: I. To describe the association between baseline gene expression levels at the protein and messenger ribonucleic acid (mRNA) level and best treatment response after two cycles of single-agent or multi-agent chemotherapy SECONDARY OBJECTIVES: I. To describe changes in protein and mRNA levels of ribonucleotide reductase M1 (RRM1), thymidylate synthetase (TS), and excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) in serial biopsies obtained from patients being treated with gemcitabine (gemcitabine hydrochloride), pemetrexed (pemetrexed disodium), and platinum. II. To describe the association between changes in marker levels and changes in tumor diameters. TERTIARY OBJECTIVES: I. To explore the relationship between marker levels in circulating tumor cells and solid tumor specimens. II. To explore the relationship between marker levels in viable peripheral blood mononuclear cells (PBMCs), circulating tumor cells, and tumor specimens. III. Should sufficient amounts and numbers of tumor specimens remain after these analyses, they will be used to assess if other genes implicated in non-small cell lung cancer (NSCLC) outcome and response to treatment might be useful as prognostic or predictive markers for patient outcome. OUTLINE: Patients receive 1 of 3 chemotherapy regimens at the discretion of the primary oncologist, including docetaxel intravenously (IV) on day 1, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After course 2, patients may continue treatment off-study at the discretion of the treating physician. After completion of study treatment, patients are followed up for 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemotherapy regimen)
Arm Type
Experimental
Arm Description
Patients receive 1 of 4 chemotherapy regimens at the discretion of the primary oncologist following institutional guidelines, including cisplatin, carboplatin, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After course 2, patients may continue treatment off-study at the discretion of the treating physician.
Intervention Type
Drug
Intervention Name(s)
docetaxel
Other Intervention Name(s)
RP 56976, Taxotere, TXT
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
pemetrexed disodium
Other Intervention Name(s)
ALIMTA, LY231514, MTA
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Other Intervention Name(s)
dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Baseline Marker Measurement
Description
A univariable regression of continuous disease response on baseline marker value will be performed. A multivariable regression model adjusted for clinical covariates will be evaluated as well. Expression levels of RRM1, TS, BRCA1, and other molecules and disease response after course 2 will be log-transformed.
Time Frame
Baseline
Secondary Outcome Measure Information:
Title
Change in Biomarker Expression Levels
Description
Evaluated using Pearson correlation. If data are not normally distributed after log transformation, a non-parametric method (e.g., Spearman correlation) will be used.
Time Frame
Baseline to up to 8 weeks (after course 2)
Title
Overall Survival (OS)
Description
Since, the study was canceled due to slow accrual, no biomarkers were measured; therefore, no analysis with biomarkers. Only the OS will be calculated.
Time Frame
From the date of protocol-specified treatment initiation to the date of death or last observation, assessed up to 12 months
Title
Progression-free Survival (PFS)
Description
Each biomarker evaluated using its expression level (continuous variable) and dichotomous form (based on a median cutoff). A univariable Cox regression model will be used to assess the relationship of expression levels of each biomarker to PFS. In addition, for the dichotomous variables, the sample will be divided into those above and below the median for each biomarker. PFS probabilities for each group will be estimated using the Kaplan-Meier method, with standard errors based on Greenwood's formula. Log rank tests will be used to determine the level of significance between survival curves. Since, the study was canceled due to slow accrual, no biomarkers were measured; therefore, no analysis with biomarkers. Only the PFS will be calculated.
Time Frame
From the date of protocol-specified treatment initiation to the date of progression, death, or last observation, assessed up to 12 months
Title
Expression Levels of Biomarkers and Other Molecules
Description
To assess the relationship between expression levels of RRM1, TS, BRCA1, and other molecules and demographic and disease variables, the Wilcoxon rank sum test or Kruskal-Wallis test for dichotomous or polychotomous categorical variables (such as sex, and histology) and the Spearman correlation coefficient for continuous ordinal variables (such as age or stage) will be used.
Time Frame
Up to 8 weeks (end of course 2)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with advanced stage NSCLC who are candidates for single or multi-agent first-line therapy. Second-line or higher therapy for any patients with NSCLC with performance status (PS) 0-2 Maintenance therapy for patients after completion of four cycles of dual-agent platinum-based chemotherapy Stage IV, histologically or cytologically confirmed NSCLC; confirmation may be obtained with the first protocol-specified tumor biopsy White blood cell count > 3000/mm^3 Platelet count > 100,000/mm^3 Hemoglobin > 9.0 g/dl A tumor lesion that can be safely biopsied as judged by the treating oncologist and physician performing the procedure and has not been radiated At least one unidimensionally measurable tumor lesion >= 1 cm in longest diameter using spiral CT (>= 2 cm in longest diameter by any other technique) that has not been radiated and is not located in a bone Performance status 0-2 by Eastern Cooperative Oncology Group criteria Life expectancy of >= 3 months Able to understand and sign the informed consent document Exclusion Criteria: Therapy that does not include cisplatin, carboplatin, gemcitabine, and/or pemetrexed Concomitant medical or psychiatric illness that is likely to interfere with a reasonably safe execution of the treatment plan Concomitant malignancy other than NSCLC that requires active therapy; prior malignancies are allowed as long as the disease is controlled and does not require ongoing therapy of any kind; prior therapy must have concluded at least 1 year before treatment initiation on this protocol; exceptions are non-melanoma skin cancer, prostate cancer and prostatic intraepithelial neoplasia (PIN) treated with local intervention and deemed cured, cervical cancer and carcinoma in situ (CIS) treated with local intervention and deemed cured, and laryngeal cancer and CIS treated with local intervention and deemed cured Carcinomatous meningitis Uncontrolled central nervous system (CNS) disease The time interval between CNS radiation, whole brain radiation, spinal cord radiation, or radiosurgery, and initiation of protocol specified chemotherapy must be at least 1 week Malignant pleural, pericardial, or peritoneal effusion if it is the only site of disease activity; i.e., if no other measurable tumor lesions exist Coagulopathy or anticoagulation therapy that cannot be safely corrected or interrupted for tumor biopsy Significant hepatic dysfunction, renal dysfunction, or metabolic derangement that precludes full-dose chemotherapy at the specified starting doses Concomitant treatment with chemotherapeutic agents for diseases other than malignancy Pregnancy or lactation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerold Bepler
Organizational Affiliation
Barbara Ann Karmanos Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Gene Expression Levels in Predicting Treatment Response in Patients With Stage IV Non-small Cell Lung Cancer

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