Ignite Creation Date:
2025-12-25 @ 1:28 AM
Ignite Modification Date:
2025-12-28 @ 12:15 AM
Study NCT ID:
NCT00454194
Status:
COMPLETED
Last Update Posted:
2017-03-21
First Post:
2007-03-27
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Pemetrexed Disodium With or Without Sorafenib as Second-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
Sponsor:
Alliance for Clinical Trials in Oncology
Organization:
Study Overview
Official Title:
Phase II Randomized Study of Pemetrexed With Sorafenib Versus Pemetrexed Alone as Second-Line Therapy in Patients With Advanced Non-Small Cell Lung Cancer
Status:
COMPLETED
Status Verified Date:
2017-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE: Pemetrexed disodium and sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving pemetrexed disodium together with sorafenib may kill more tumor cells.
PURPOSE: This randomized phase II trial is studying pemetrexed disodium and sorafenib to see how well they work compared with pemetrexed disodium alone as second-line therapy in treating patients with stage IIIB or stage IV non-small cell lung cancer.
PURPOSE: This randomized phase II trial is studying pemetrexed disodium and sorafenib to see how well they work compared with pemetrexed disodium alone as second-line therapy in treating patients with stage IIIB or stage IV non-small cell lung cancer.
Detailed Description:
OBJECTIVES:
Primary
* Compare the progression-free survival of patients with stage IIIB or IV non-small cell lung cancer treated with pemetrexed disodium with or without sorafenib tosylate as second-line therapy.
Secondary
* Compare the overall survival of patients treated with these regimens.
* Compare the tumor response rate and duration of response in patients treated with these regimens.
* Compare the toxicity profile of these regimens in these patients.
Tertiary
* Assess polymorphisms and gene expression in circulating peripheral mononuclear cells and circulating tumor cells of pemetrexed disodium target genes and genes encoding enzymes involved in the transport, activation, and inactivation of pemetrexed disodium.
* Correlate haplotype-tagged single nucleotide polymorphisms or gene expression levels with intracellular levels of pemetrexed disodium polyglutamates, toxicity, and/or efficacy of pemetrexed disodium.
* Assess the expression and polymorphisms in the target genes (i.e., TS, DHFR, GARFT) and methylthioadenosine phosphorylase (as antibodies become available) in paraffin-embedded tissue and compare results to those obtained in circulating tumor tissue, correlating results with response.
* Correlate predictive markers of hypertension (e.g. pharmacogenetics, vascular endothelial growth factor \[VEGF\]-A, sVEGF receptor-1, and ADMA) with clinical toxicity and outcomes.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1) and North Central Cancer Treatment Group membership. Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive oral sorafenib tosylate twice daily on days 1-21 and pemetrexed disodium IV over 10 minutes on day 1.
* Arm II: Patients receive pemetrexed disodium IV over 10 minutes on day 1. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and tissue samples are collected for pharmacokinetic analysis and research studies. Gene expression assays and polymorphism studies (e.g., using polymerase chain reaction) of circulating peripheral blood mononuclear cells are conducted for reduced folate carrier, multidrug resistance-associated protein, folate receptor, BCRP, folylpolyglutamate synthase, MTHFR, methionine synthase, methylthioadenosine phosphorylase, TS, dihydrofolate reductase, GARFT, endothelial nitric oxide synthase, angiotensinogen, dimethylarginine dimethylaminohydrolase, vascular endothelial growth factor (VEGF), and VEGF receptor. Enzyme-linked immunosorbent assays and immunohistochemistry are also conducted.
After completion of study treatment, patients are followed periodically for up to 5 years.
Primary
* Compare the progression-free survival of patients with stage IIIB or IV non-small cell lung cancer treated with pemetrexed disodium with or without sorafenib tosylate as second-line therapy.
Secondary
* Compare the overall survival of patients treated with these regimens.
* Compare the tumor response rate and duration of response in patients treated with these regimens.
* Compare the toxicity profile of these regimens in these patients.
Tertiary
* Assess polymorphisms and gene expression in circulating peripheral mononuclear cells and circulating tumor cells of pemetrexed disodium target genes and genes encoding enzymes involved in the transport, activation, and inactivation of pemetrexed disodium.
* Correlate haplotype-tagged single nucleotide polymorphisms or gene expression levels with intracellular levels of pemetrexed disodium polyglutamates, toxicity, and/or efficacy of pemetrexed disodium.
* Assess the expression and polymorphisms in the target genes (i.e., TS, DHFR, GARFT) and methylthioadenosine phosphorylase (as antibodies become available) in paraffin-embedded tissue and compare results to those obtained in circulating tumor tissue, correlating results with response.
* Correlate predictive markers of hypertension (e.g. pharmacogenetics, vascular endothelial growth factor \[VEGF\]-A, sVEGF receptor-1, and ADMA) with clinical toxicity and outcomes.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1) and North Central Cancer Treatment Group membership. Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive oral sorafenib tosylate twice daily on days 1-21 and pemetrexed disodium IV over 10 minutes on day 1.
* Arm II: Patients receive pemetrexed disodium IV over 10 minutes on day 1. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and tissue samples are collected for pharmacokinetic analysis and research studies. Gene expression assays and polymorphism studies (e.g., using polymerase chain reaction) of circulating peripheral blood mononuclear cells are conducted for reduced folate carrier, multidrug resistance-associated protein, folate receptor, BCRP, folylpolyglutamate synthase, MTHFR, methionine synthase, methylthioadenosine phosphorylase, TS, dihydrofolate reductase, GARFT, endothelial nitric oxide synthase, angiotensinogen, dimethylarginine dimethylaminohydrolase, vascular endothelial growth factor (VEGF), and VEGF receptor. Enzyme-linked immunosorbent assays and immunohistochemistry are also conducted.
After completion of study treatment, patients are followed periodically for up to 5 years.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: