Carboplatin and Etoposide in Combination With Vorinostat for Patients With Extensive Stage Small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT00702962|
Recruitment Status : Terminated (Poor accrual)
First Posted : June 20, 2008
Results First Posted : October 15, 2018
Last Update Posted : October 22, 2018
|Condition or disease||Intervention/treatment||Phase|
|Small Cell Lung Cancer||Drug: Vorinostat, Carboplatin, Etoposide||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of Carboplatin and Etoposide in Combination With Vorinostat for Patients With Extensive Stage Small Cell Lung Cancer|
|Actual Study Start Date :||September 2008|
|Actual Primary Completion Date :||July 2012|
|Actual Study Completion Date :||July 2012|
Experimental: Phase I: Vorinostat 200 mg
Vorinostat 200 mg PO QD D1-14; Administer with Carbo 6 (AUC) D3; Etoposide 100 mg/m2 D1,2,3 "Vorinostat", "Carboplatin", "Etoposide"
Drug: Vorinostat, Carboplatin, Etoposide
Study originally a Phase I standard dose escalation of the study medication Vorinostat with sequential cohorts of 3-6 participants entered to 3 dose levels (200mg, 300mg, 400mg). Dose escalation stopped after participant 1 on dose level 2 due to recently published research identifying an appropriate dosing regimen. A set dose was then to be administered to all subsequent participants. This regimen (a "cycle") consisted of Vorinostat on Day 1 through Day 4, Carboplatin AUC 6 on Day 3, and Etoposide 100 mg/m2 on Day 3 through Day 5. Treatment cycles were repeated every 21 days (3 weeks) for 4 cycles total.
Other Name: Suberoyl anilide hydroxamic acid (SAHA)
- Assess Maximum Tolerated Dose of Vorinostat When Combined With Carboplatin and Etoposide of Patients With Extensive Disease SCLC [ Time Frame: 2 years, not analyzed ]To estimate the maximum tolerated dose of vorinostat using a traditional dose escalation schedule ("3 + 3 design). MTD is determined by assessing for specific predefined dose limiting toxicities. A starting dose of vorinostat 200mg was combined with carboplatin and etoposide. Dose escalation went in increments of 100mg (i.e. 300mg, 400mg).
- To Evaluate Overall Survival of Patients With Extensive Disease SCLC Receiving Carboplatin, Etoposide, and a Fixed Dose (300mg) of Vorinostat [ Time Frame: 2 years, not analyzed ]For the purpose of this study, overall survival is defined as the percentage of participants who are alive at two years post initiation of study treatment.
- Evaluate Objective Response Rate Among Patients With Extensive Disease SCLC Receiving Carboplatin and Etoposide With a Fixed Dose of Vorinostat. [ Time Frame: 2 years, not analyzed ]Eligibility limits the study population to those who have measurable disease pre-treatment. This secondary outcome measure was intended to objectively evaluate disease response and survival rate in recipients of the investigational medication regimen. Disease response was performed using standard diagnostic imaging. Tumor markers and cytology may be used to support the imaging results. Objective response rate was defined as progression-free survival (PFS) among treatment recipients. PFS, is defined as time (in months) from entry to clinical evidence of disease progression or death without progression. The clinical trial closed prematurely due to low accrual. For this reason, an analysis of this secondary objective would not be meaningful. No analysis done.
- To Assess the Safety Profile and Define the Toxicities of Using a Fixed Dose (300mg) of Vorinostat With Carboplatin and Etoposide [ Time Frame: 2 years, not analyzed ]Evaluation of resultant adverse events that occurred with participants with extensive disease SCLC after initiating treatment using a fixed dose of vorinostat in combination with carboplatin and etoposide.
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|