Pemetrexed Disodium With or Without Sorafenib as Second-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
- Registration Number
- NCT00454194
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 110
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I pemetrexed disodium Patients receive oral sorafenib tosylate twice daily on days 1-21 and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm I sorafenib tosylate Patients receive oral sorafenib tosylate twice daily on days 1-21 and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm II pemetrexed disodium Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-free Survival Time from randomization to the disease progression or death (up to 5 years) The progression-free survival (PFS) was defined as the time from date of randomization to the documentation of disease progression or death as a result of any cause, whichever comes first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
- Secondary Outcome Measures
Name Time Method Time to Treatment Failure Up to 5 years Time to treatment failure was defined as the time from date of randomization to the date at which the patient was removed from the treatment due to progression, toxicity, refusal or other medical problems.
Overall Survival Time from randomization to death or last follow-up (up to 5 years) Overall survival was defined as the time from study enrollment (randomization) to the time of death from any cause or last follow-up.
Duration of Response Up to 5 years Duration of response was defined as the time from the date at which the patient's earliest best objective status was first noted to be either a complete response (CR) or partial response (PR) to the earliest date progression was documented.
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:
* Complete Response (CR): disappearance of all target lesions;
* Partial Response (PR) 30% decrease in sum of longest diameter of target lesions;Number of Participants With at Least One Grade 3 or Above Adverse Events Assessed by NCI CTCAE v4.0 Up to 3 years Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death. The maximum grade for each type of adverse events were recorded for each patient.
Confirmed Response Rate (Complete Response and Partial Response) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Up to 5 years A confirmed tumor response was defined as a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 6 weeks apart.
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:
* Complete Response (CR): disappearance of all target lesions;
* Partial Response (PR) 30% decrease in sum of longest diameter of target lesions;
* Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions;
* Stable Disease (SD): small changes that do not meet above criteria.
Trial Locations
- Locations (204)
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
Aurora Presbyterian Hospital
🇺🇸Aurora, Colorado, United States
Boulder Community Hospital
🇺🇸Boulder, Colorado, United States
Penrose Cancer Center at Penrose Hospital
🇺🇸Colorado Springs, Colorado, United States
St. Anthony Central Hospital
🇺🇸Denver, Colorado, United States
Porter Adventist Hospital
🇺🇸Denver, Colorado, United States
Presbyterian - St. Luke's Medical Center
🇺🇸Denver, Colorado, United States
St. Joseph Hospital
🇺🇸Denver, Colorado, United States
Rose Medical Center
🇺🇸Denver, Colorado, United States
CCOP - Colorado Cancer Research Program
🇺🇸Denver, Colorado, United States
Scroll for more (194 remaining)Mayo Clinic Scottsdale🇺🇸Scottsdale, Arizona, United States