Carboplatin and Etoposide in Combination With Vorinostat for Patients With Extensive Stage Small Cell Lung Cancer
|Small Cell Lung Cancer||Drug: Vorinostat, Carboplatin, Etoposide Other: SAHA||Phase 1 Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Carboplatin and Etoposide in Combination With Vorinostat for Patients With Extensive Stage Small Cell Lung Cancer|
- Assess maximum tolerated dose of vorinostat combined with carboplatin + etoposide for patients with extensive disease SCLC. [ Time Frame: An expected average of 2 years ]
- Evaluate overall survival & objective response rate among patients with extensive disease SCLC receiving carboplatin + etoposide with vorinostat. [ Time Frame: An expected average of 2 years ]
|Actual Study Start Date:||September 2008|
|Study Completion Date:||July 2012|
|Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
Experimental: 1 Vorinostat 200mg Carbo 6 (AUC)
Vorinostat 200 mg PO QD D1-14; Carbo 6 (AUC) D3; Etoposide 100 mg/m2 D1,2,3 Vorinostat, Carboplatin, Etoposide, SAHA
Drug: Vorinostat, Carboplatin, Etoposide
Sequential cohorts of 3-6 patients will be entered to the following dose levels: Level 1 - Days 1-14: Vorinostat 200 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Level 2 - Days 1-14: Vorinostat 300 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2; Level 3: Days 1-14: Vorinostat 400 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each patient.
Other Name: SAHA
2 Vorinostat 300mg Carbo 6 (AUC)
Phase 2 is to determine progression free survival among patients with extensive disease SCLC receiving carboplatin plus etoposide with vorinostat.Vorinostat, Carboplatin, Etoposide, SAHA
Once the recommended phase II dose has been established and additional 15 patients will be enrolled. Days 1-4 Vorinostat recommended phase II dose po QD;Day 3 Carboplatin 6 AUC; Days 1,2,3 Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each patient. An additional 35 patients on the phase II portion of the trial will be required to achieve the outlined objectives.
Other Name: Vorinostat, Carboplatin, Etoposide
Vorinostat inhibits growth and induces apoptosis in various human carcinoma cells. Furthermore, it affects the expression of various genes that are necessary for proliferation of cancer cells. Vorinostat also appears to block angiogenic signaling. Pre-treating four human cancer cell lines (including a brain tumor line) with vorinostat increased the killing efficiency of etoposide, ellipticine, doxorubicin, or cisplatin, but not of the topoisomerase I inhibitor camptothecin 13. Topoisomerase II is a ubiquitous nuclear enzyme that is involved in DNA replication, transcription, chromosome segregation, and apoptosis. It is the target for several anti-cancer drugs including etoposide. Treatment with HDAC inhibitors induces expression of topoisomerase II in cancer cells and enhances the sensitivity to etoposide 14.
Early phase clinical trials have demonstrated single agent anti-cancer activity with vorinostat. In our study, combination of vorinostat with carboplatin and paclitaxel, demonstrated promising anticancer activity against NSCLC, including histological subsets of patients whose tumors demonstrated neuroendocrine differentiation 8. For all these reasons, vorinostat is a rational choice to combine with the regimen of carboplatin and etoposide for evaluation in patients with SCLC-ED.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00702962
|United States, Pennsylvania|
|Penn State College of Medicine, Penn State Milton S. Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033|
|Principal Investigator:||Chandra P Belani, MD||Penn State College of Medicine|