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Sponsors and Collaborators: |
Penn State University Merck |
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Information provided by: | Penn State University |
ClinicalTrials.gov Identifier: | NCT00702962 |
The Phase I portion of the study is to assess the maximum tolerated dose of vorinostat when combined with carboplatin plus etoposide. The Phase II portion is to determine progression-free survival among patients with extensive disease small cell lung cancer receiving carboplatin plus etoposide with vorinostat.
Condition | Intervention | Phase |
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Small Cell Lung Cancer |
Drug: Vorinostat, Carboplatin, Etoposide Other: Vorinostat, Carboplatin, Etoposide |
Phase I Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Open Label, Factorial Assignment, Efficacy Study |
Official Title: | Phase I/II Study of Carboplatin and Etoposide in Combination With Vorinostat for Patients With Extensive Stage Small Cell Lung Cancer |
Estimated Enrollment: | 20 |
Study Start Date: | September 2008 |
Estimated Study Completion Date: | September 2012 |
Estimated Primary Completion Date: | September 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
Dose escalation scheme
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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.
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2
Phase 2 is to determine progression free survival among patients with extensive disease SCLC receiving carboplatin plus etoposide with vorinostat.
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Other: Vorinostat, Carboplatin, Etoposide
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.
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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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, Pennsylvania | |
Penn State College of Medicine, Penn State Milton S. Hershey Medical Center | Recruiting |
Hershey, Pennsylvania, United States, 17033 | |
Contact: Chandra P Belani, MD 717-531-1078 cbelani@psu.edu | |
Principal Investigator: Chandra P Belani, MD |
Principal Investigator: | Chandra P Belani, MD | Penn State College of Medicine |
Responsible Party: | Penn State Hershey Cancer Institute ( Chandra P. Belani, MD ) |
Study ID Numbers: | PSHCI 08-005 |
Study First Received: | June 19, 2008 |
Last Updated: | October 9, 2008 |
ClinicalTrials.gov Identifier: | NCT00702962 |
Health Authority: | United States: Institutional Review Board |
lung cancer small cell lung cancer |
Thoracic Neoplasms Carcinoma, Neuroendocrine Vorinostat Carboplatin Etoposide phosphate Carcinoma Neuroendocrine Tumors Carcinoma, Small Cell Neuroectodermal Tumors |
Respiratory Tract Diseases Lung Neoplasms Lung Diseases Neoplasms, Germ Cell and Embryonal Neuroepithelioma Adenocarcinoma Etoposide Neoplasms, Glandular and Epithelial |
Anticarcinogenic Agents Anti-Inflammatory Agents Respiratory Tract Neoplasms Neoplasms by Histologic Type Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Physiological Effects of Drugs Neoplasms, Nerve Tissue Enzyme Inhibitors Protective Agents Pharmacologic Actions |
Neoplasms Neoplasms by Site Analgesics, Non-Narcotic Sensory System Agents Therapeutic Uses Anti-Inflammatory Agents, Non-Steroidal Peripheral Nervous System Agents Analgesics Antirheumatic Agents Central Nervous System Agents Antineoplastic Agents, Phytogenic |