Bortezomib and Pemetrexed Disodium in Treating Patients With Advanced Non-Small Cell Lung Cancer or Other Solid Tumors
RATIONALE: Bortezomib and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with pemetrexed disodium may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of two different schedules of bortezomib when given together with pemetrexed disodium and to see how well they work in treating patients with advanced non-small cell lung cancer or other solid tumors.
|Lung Cancer Unspecified Adult Solid Tumor, Protocol Specific||Drug: bortezomib Drug: pemetrexed disodium Genetic: gene expression analysis Genetic: mutation analysis Genetic: protein expression analysis Genetic: reverse transcriptase-polymerase chain reaction Other: flow cytometry Other: immunoenzyme technique Other: immunohistochemistry staining method||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Two Different Schedules of Bortezomib (VELCADE, PS-341) and Pemetrexed (ALIMTA) in Advanced Solid Tumors, With Emphasis on Non-Small Cell Lung Cancer (NSCLC)|
- Number of Patients Experiencing a Dose-limiting Toxicity (Phase I) [ Time Frame: Up to 36 months ]Grade 4 thrombocytopenia or grade 3 thrombocytopenia associated with bleeding, requirement for transfusion or lasting >7 days; febrile neutropenia; grade 3 neutropenia associated with infection; any other grade >/=3 non-hematologic toxicity considered by the investigator to be related to study drug.
- Number of Participants Who Experience Adverse Events (Phase I) [ Time Frame: Throughout the entire study (up to 36 months). ]Number of participants with treatment-related adverse events as assessed by CTCAE v3.0 (Phase I).
- Number of Patients With Grade ≥ 3 Toxicity (Phase I) [ Time Frame: First cycle of treatment (3 weeks) ]Grade 3/4 toxicity occurring in a patient within 1 cycle.
- Number of Patients Who Responded to Study Treatment (Phase II) [ Time Frame: From start of treatment until disease progression/recurrence. ]To determine the response rate of bortezomib in combination with pemetrexed in patients with advanced NSCLC. Response rate was assessed by CT scan. CT scans was performed at baseline and every two cycles (prior to 3rd and 5th cycle). The evaluation of response was based on standard RECIST criteria.
- Number of Patients With Toxicity by NCI CTC v3.0 (Phase I) [ Time Frame: Up to 36 months ]Adverse events possibly related to treatment, graded according to the NCI CTCAE v3.0.
- Maximum Tolerated Dose of Bortezomib in Combination With Pemetrexel (Phase I) [ Time Frame: Up to 36 months ]
- Treatment Efficacy as Measured by RECIST (Phase I) [ Time Frame: Up to 36 months ]Response to therapy was evaluated every 2 cycles according to RECIST criteria.
- Number of Participants With Toxicities (Phase II) [ Time Frame: Up to 36 months ]Each adverse event will be determined by using the NCI CTCAE, Version 3.0.
- Analysis of Molecular Determinants in Tumor Samples (Phase II) [ Time Frame: Up to 36 months ]Expression of relevant molecular targets of the proteasome, which is inhibited by bortezomib.
- Importance of Folate-associated Gene Expression and Response or Outcome (Phase II) [ Time Frame: Up to 36 months ]Overexpression of reduced folate carrier (RFC) protein is thought to contribute to decreased resistance to pemetrexed. Levels of expression will be studied by measuring mRNA transcripts using quantitative Reverse Transcriptase-Polymerase Chain Reaction in archival patient tumor specimens.
- Effect of Bortezomib on Over Expression of NF-kB, BCL-2, and BCL-xL (Phase II) [ Time Frame: Up to 36 months ]Tumor levels of BCL-2, BCL-xL and BAX will be assessed by immunohistochemistry (IHC).
|Study Start Date:||March 2005|
|Study Completion Date:||June 2007|
|Primary Completion Date:||December 2006 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00389805
|United States, California|
|University of California Davis Cancer Center|
|Sacramento, California, United States, 95817|
|Study Chair:||Angela Davies, MD||University of California, Davis|