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

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ClinicalTrials.gov Identifier: NCT02145078
Recruitment Status : Terminated (Slow accrual.)
First Posted : May 22, 2014
Results First Posted : September 24, 2020
Last Update Posted : September 24, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Gerold Bepler, Barbara Ann Karmanos Cancer Institute

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.

Condition or disease Intervention/treatment Phase
Recurrent Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer Drug: docetaxel Drug: pemetrexed disodium Drug: gemcitabine hydrochloride Other: laboratory biomarker analysis Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : June 2014
Actual Primary Completion Date : June 18, 2015
Actual Study Completion Date : March 7, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (chemotherapy regimen)
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.
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT

Drug: pemetrexed disodium
Given IV
Other Names:
  • ALIMTA
  • LY231514
  • MTA

Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar

Other: laboratory biomarker analysis
Correlative studies




Primary Outcome Measures :
  1. Baseline Marker Measurement [ Time Frame: Baseline ]
    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 :
  1. Change in Biomarker Expression Levels [ Time Frame: Baseline to up to 8 weeks (after course 2) ]
    Evaluated using Pearson correlation. If data are not normally distributed after log transformation, a non-parametric method (e.g., Spearman correlation) will be used.

  2. Overall Survival (OS) [ Time Frame: From the date of protocol-specified treatment initiation to the date of death or last observation, assessed up to 12 months ]
    Since, the study was canceled due to slow accrual, no biomarkers were measured; therefore, no analysis with biomarkers. Only the OS will be calculated.

  3. Progression-free Survival (PFS) [ Time Frame: From the date of protocol-specified treatment initiation to the date of progression, death, or last observation, assessed up to 12 months ]
    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.

  4. Expression Levels of Biomarkers and Other Molecules [ Time Frame: Up to 8 weeks (end of course 2) ]
    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.



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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02145078


Locations
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United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Gerold Bepler Barbara Ann Karmanos Cancer Institute
  Study Documents (Full-Text)

Documents provided by Gerold Bepler, Barbara Ann Karmanos Cancer Institute:
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Responsible Party: Gerold Bepler, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT02145078    
Other Study ID Numbers: 2013-177
NCI-2014-01023 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
1402012854
2013-177 ( Other Identifier: Barbara Ann Karmanos Cancer Institute )
P30CA022453 ( U.S. NIH Grant/Contract )
First Posted: May 22, 2014    Key Record Dates
Results First Posted: September 24, 2020
Last Update Posted: September 24, 2020
Last Verified: September 2020
Additional relevant MeSH terms:
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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
Gemcitabine
Docetaxel
Pemetrexed
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors