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

• ClinicalTrials.gov Identifier: NCT00898820
• Recruitment Status: Completed
• First Posted: May 12, 2009
• Last Update Posted: April 9, 2014
• Sponsor: Mayo Clinic
• Collaborator: National Cancer Institute (NCI)
• Information provided by: Mayo Clinic

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Lung Cancer	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 Design

• Study Type: Observational
• Estimated Enrollment: 80 participants
• Official Title: Predictive Markers of Response to Pemetrexed (Companion Study to RC0524)
• Study Start Date: November 2006
• Actual Primary Completion Date: December 2007
• Actual Study Completion Date: December 2007

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

• Study Chair: Julian Molina, MD, PhD; Mayo Clinic
• Principal Investigator: Elizabeth A. Johnson, M.D.; Mayo Clinic

More Information

• Responsible Party: Julian R. Molina, M.D., Ph.D., Mayo Clinic Cancer Center
• ClinicalTrials.gov Identifier: NCT00898820
• Other Study ID Numbers: RC0527; P30CA015083 ( U.S. NIH Grant/Contract ); RC0527 ( Other Identifier: Mayo Clinic Cancer Center & MCCRC ); 06-002282 ( Other Identifier: Mayo Clinic IRB )
• First Posted: May 12, 2009
• Last Update Posted: April 9, 2014
• Last Verified: April 2014

Keywords provided by Mayo Clinic:

stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; recurrent non-small cell lung cancer

Additional relevant MeSH terms:

Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases