Tumor Response to Pemetrexed Disodium in Patients With Stage III or Stage IV Non-Small Cell Lung Cancer Enrolled in Clinical Trial MCCRC-RC0524

Predictive Markers of Response to Pemetrexed (Companion Study to RC0524)

RATIONALE: Studying samples of blood in the laboratory from patients receiving pemetrexed disodium may help doctors learn more about the effects of pemetrexed disodium on cells. It may also help doctors understand how well patients respond to treatment.

PURPOSE: This laboratory study is looking at blood samples from patients with stage III or stage IV non-small cell lung cancer enrolled in clinical trial MCCRC-RC0524 to determine the effect of pemetrexed disodium on cells.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Genetic: gene expression analysis; Genetic: polymorphism analysis; Genetic: protein expression analysis

Detailed Description

OBJECTIVES:

Primary

• Assess the intracellular level of pemetrexed disodium (PD) polyglutamates as a measure of activity of PD transport and activation enzymes in patients with stage III or IV non-small cell lung cancer enrolled in clinical trial MCCRC-RC0524.

Secondary

• Assess polymorphisms and gene expression of PD target genes and genes encoding enzymes involved in the transport, activation, and inactivation of PD in these patients.
• Correlate haplotype-tagged single-nucleotide polymorphisms (htSNPs) and gene expression levels with intracellular levels of PD polyglutamates
• Correlate htSNPs and gene expression levels with toxicity and efficacy of PD.

OUTLINE: Blood is drawn prior to and 24 hours after day 1 of course 1 of pemetrexed disodium. DNA is extracted and genotyped for known polymorphisms in genes involved in the transport, activation, inactivation, and mechanism of action or resistance of pemetrexed disodium, including reduced folate carrier-1, multiresistance proteins (particularly MRP5), folate receptor, folypolyglutamate synthase, methylenetetrahydrofolate reductase (MTHFR), methionine synthase, methylthioadenosine phosphorylase, thymidylate synthase (TS), dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. Plasma and red blood cells are also processed for an intracellular polyglutamate assay for pemetrexed disodium by a high-performance liquid chromatography-based method.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

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

DISEASE CHARACTERISTICS:

• Enrolled in clinical trial MCCRC-RC0524
• Willing to provide blood samples

PATIENT CHARACTERISTICS:

• No investigator site personnel directly affiliated with the study, or immediate family of investigator site personnel directly affiliated with the study

  • Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted

• Not employed by Eli Lilly (i.e., employee, temporary contract worker, or designee responsible for conducting the study)

  • Immediate family of Eli Lilly employees allowed, but may not participate at an Eli Lilly facility

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Activity of pemetrexed disodium (PD) transport and activation enzymes as measured by intracellular content of PD polyglutamates

Secondary Outcome Measures

Outcome Measure
Polymorphisms and gene expression of PD target genes (RFC-1, MRP, folate receptor, FPGS, methylenetetrahydrofolate reductase, methionine synthase, methylthioadenosine phosphorylase, TS, DHFR, GARFT)
Polymorphisms and gene expression of genes encoding enzymes involved in the transport, activation, and inactivation of PD
Correlation of haplotype-tagged single-nucleotide polymorphisms (htSNPs) and gene expression levels with intracellular levels of PD polyglutamates
Correlation of htSNPs and gene expression levels with toxicity and efficacy of PD

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Elizabeth A. Johnson, M.D., Mayo Clinic

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: May 9, 2009
• First Submitted That Met QC Criteria: May 9, 2009
• First Posted (Estimate): May 12, 2009

Study Record Updates

• Last Update Posted (Estimate): April 9, 2014
• Last Update Submitted That Met QC Criteria: April 7, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: RC0527 (Other Identifier: Mayo Clinic Cancer Center & MCCRC); P30CA015083 (U.S. NIH Grant/Contract); 06-002282 (Other Identifier: Mayo Clinic IRB)