Ignite Creation Date:
2024-05-05 @ 5:30 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00466232
Status:
COMPLETED
Last Update Posted:
2015-12-16
First Post:
2007-04-24
Brief Title:
Phase I Study of Weekly Topotecan in Combination With Sorafenib in Treatment of Relapsed Small Cell Lung Cancer
Sponsor:
HealthPartners Institute
Organization:
HealthPartners Institute
Study Overview
Official Title:
Phase I Study of Weekly Topotecan in Combination With Sorafenib in Treatment of Relapsed Small Cell Lung Cancer
Status:
COMPLETED
Status Verified Date:
2007-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The primary objective of this study is to determine the maximum tolerated dose of sorafenib up to the full active dose when combined with standard weekly dosing of topotecan in patients with recurrent small cell lung cancer and to characterize the toxicities associated with the combination of topotecan and sorafenib in this patient population
Detailed Description:
Small cell lung cancer SCLC comprises approximately 15 percent of all lung cancers in the United States It is highly correlated with tobacco use and occurs almost exclusively in smokers SCLC is a particularly virulent malignancy characterized by rapid growth and a tendency to metastasize early in the disease course In first line treatment SCLC has a high response rate to cytotoxic chemotherapy Unfortunately the disease develops drug resistance in almost all cases resulting in recurrence In second line treatment the likelihood of response to treatment is considerably less Multiple agents have been used in this setting with response rates typically around 25 and median survival of less than 6 months1-3 There is clearly a great need for more effective treatments in this disease
Topotecan is a semi-synthetic water soluble derivative of camptothecin a cytotoxic alkaloid extracted from plants of the genus Camptotheca Its mechanism of action is inhibition of topoisomerase I an enzyme necessary to relieve torsional strain of DNA which is necessary to carry out replication This results in DNA double-strand breaks and ultimately cell death Topotecan has demonstrated activity in a number of malignancies and is currently indicated for the treatment of ovarian cancer cervical cancer and recurrent small cell lung cancer
Topotecan has demonstrated single agent activity in recurrent small cell lung cancer in a number of trials Reported response rates range from 2 to 313-7 A phase III trial compared topotecan to CAV cyclophosphamide doxorubicin and vincristine in treatment of recurrent SCLC5 Response rate survival and time to progression were similar in both groups The topotecan group demonstrated significant improvement in symptoms including anorexia fatigue and dyspnea This led to FDA approval of topotecan for treatment of recurrent SCLC
The dose limiting toxicity of topotecan is hematologic The approved schedule of administration is 15mgm2 daily x 5 every 21 days A modified schedule of weekly administration at 4mgm2 has been shown to have similar efficacy with less toxicity8 and has been widely adopted in clinical practice
Sorafenib is an oral multi-kinase inhibitor with effects on tumor proliferation and tumor angiogenesis It has several biochemically important mechanisms including inhibition of Raf-1 and B-Raf which are pivotal components of the RasRafMekErk signaling pathway It also has inhibitory activity against the tyrosine kinases for VEGF and PDGFR as well as Flt-3 and c-kit
Sorafenib has been safely combined with full dose cytotoxic chemotherapy in several Phase I trials9-11 There is no data on the combination of topotecan and sorafenib to date Sorafenib is metabolized in the liver undergoing oxidation via CYP3A4 and glucuronidation via UGT1A9 There is no evidence that topotecan affects activity of the cytochrome P450 pathways suggesting low likelihood of a drug-drug interaction There are no significant overlapping toxicities making this an ideal drug combination to investigate
Topotecan is a semi-synthetic water soluble derivative of camptothecin a cytotoxic alkaloid extracted from plants of the genus Camptotheca Its mechanism of action is inhibition of topoisomerase I an enzyme necessary to relieve torsional strain of DNA which is necessary to carry out replication This results in DNA double-strand breaks and ultimately cell death Topotecan has demonstrated activity in a number of malignancies and is currently indicated for the treatment of ovarian cancer cervical cancer and recurrent small cell lung cancer
Topotecan has demonstrated single agent activity in recurrent small cell lung cancer in a number of trials Reported response rates range from 2 to 313-7 A phase III trial compared topotecan to CAV cyclophosphamide doxorubicin and vincristine in treatment of recurrent SCLC5 Response rate survival and time to progression were similar in both groups The topotecan group demonstrated significant improvement in symptoms including anorexia fatigue and dyspnea This led to FDA approval of topotecan for treatment of recurrent SCLC
The dose limiting toxicity of topotecan is hematologic The approved schedule of administration is 15mgm2 daily x 5 every 21 days A modified schedule of weekly administration at 4mgm2 has been shown to have similar efficacy with less toxicity8 and has been widely adopted in clinical practice
Sorafenib is an oral multi-kinase inhibitor with effects on tumor proliferation and tumor angiogenesis It has several biochemically important mechanisms including inhibition of Raf-1 and B-Raf which are pivotal components of the RasRafMekErk signaling pathway It also has inhibitory activity against the tyrosine kinases for VEGF and PDGFR as well as Flt-3 and c-kit
Sorafenib has been safely combined with full dose cytotoxic chemotherapy in several Phase I trials9-11 There is no data on the combination of topotecan and sorafenib to date Sorafenib is metabolized in the liver undergoing oxidation via CYP3A4 and glucuronidation via UGT1A9 There is no evidence that topotecan affects activity of the cytochrome P450 pathways suggesting low likelihood of a drug-drug interaction There are no significant overlapping toxicities making this an ideal drug combination to investigate
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None