Lenalidomide and GM-CSF in Treating Patients With Prostate Cancer
RATIONALE: Lenalidomide may stop the growth of prostate cancer by blocking blood flow to the tumor. GM-CSF may stimulate the immune system in different ways and stop tumor cells from growing. Giving lenalidomide together with GM-CSF may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of lenalidomide when given together with GM-CSF and to see how well it works in treating patients with prostate cancer.
|Prostate Cancer||Biological: sargramostim Drug: lenalidomide Other: laboratory biomarker analysis||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Lenalidomide (RevlimidTM ) and GM-CSF in Androgen Independent Prostate Cancer|
- Number of Patients With a PSA Response [ Time Frame: reevaluated for response every eight weeks ]Number of patients with a PSA Response defined as a PSA decline greater or equal to 50% compared with baseline value.
- RECIST-defined Measurable Disease [ Time Frame: every 8 weeks and at end of treatment ]Patients who have a response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) by RECIST criteria. To be assigned a status of PR or CR, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met. In the case of SD, follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 6-8 weeks
- Number of Patients With Statistically Significant Change in Immune Response From Baseline to End of Study [ Time Frame: every 28 days for first 3 cycles, end of study ]The change in mean T cell immunohistochemical markers and dendritic cells over time will be evaluated using analysis of variance methods for repeated measures with additional main factors included in the analysis for subset comparisons. The pattern of immune response will be evaluated based upon overall clinical response using these same techniques.
|Study Start Date:||July 2005|
|Study Completion Date:||December 2012|
|Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
|Experimental: Lenalidomide (RevlimidTM ) and GM-CSF||
All patients will receive GM-CSF at a dose of 250 mcg subcutaneously on Mondays, Wednesdays and Fridays every week. No dose escalation or de-escalations will be made to GM-CSF.
Other Name: GM-CSFDrug: lenalidomide
Lenalidomide will be administered at 25 mg/day orally on days 1-21 of a 28-day cycle. Initially 6 patients will be entered at the 25 mg/day level. If 0 or 1 patients have a dose limiting toxicity, then the 25 mg lenalidomide + GM-CSF 250 mcg subcutaneously on Mondays, Wednesdays and Fridays every week will be accepted as the phase II dose.Other: laboratory biomarker analysis
Prior to the initiation of each cycle of therapy for the first 3 cycles, and at discontinuation from study blood will be collected for assessments of a prostate cancer specific immune response.
- Establish the safety of a predetermined target dose or, if the target dose is not tolerable, find the maximum tolerated dose of lenalidomide when administered in combination with sargramostim in patients with androgen-independent prostate cancer.
- Evaluate the preliminary efficacy of this regimen to ascertain whether additional study of lenalidomide is warranted in patients with androgen-independent prostate cancer.
- Evaluate the safety of this regimen in these patients.
- Describe the effects of this regimen on serum cytokines (e.g., TNF-α, bFGF, sIL2R, IL-8, and IL-12) and on serum VEGF levels.
- Assess the co-stimulatory effects of this regimen on CD4+, CD8+, CD83, and CD86 cells.
OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II study.
Patients receive oral lenalidomide on days 1-21 and sargramostim subcutaneously on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for correlative biomarker and immunological laboratory studies.
After completion of study therapy, patients are followed up at 30 days and then every 3 months thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00939510
|United States, Ohio|
|Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Principal Investigator:||Robert Dreicer, MD, FACP||Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|