Ignite Creation Date:
2024-05-05 @ 10:44 PM
Last Modification Date:
2024-10-26 @ 10:23 AM
Study NCT ID:
NCT01175096
Status:
UNKNOWN
Last Update Posted:
2010-08-04
First Post:
2010-08-02
Brief Title:
Safety and Tolerability Profile of RAD001 Daily in Chinese Patients With Advanced Pulmonary Neuroendocrine Tumor
Sponsor:
Guangdong Provincial Peoples Hospital
Organization:
Guangdong Provincial Peoples Hospital
Study Overview
Official Title:
A Phase Ib Open-label Study to Evaluate RAD001 as Monotherapy Treatment in Chinese Patients With Advanced Pulmonary Neuroendocrine Tumor
Status:
UNKNOWN
Status Verified Date:
2010-05
Last Known Status:
ACTIVE_NOT_RECRUITING
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:
RAD001 continues to be investigated as an anticancer agent on new indications such as neuroendocrine tumors incl carcinoid breast cancer liver cancer gastric cancer and lymphoma based on its potential to act
directly on the tumor cells by inhibiting tumor cell growth and proliferation
indirectly by inhibiting angiogenesis leading to reduced tumor vascularity via potent inhibition of tumor cell HIF-1 activity and VEGF production and VEGF-induced proliferation of endothelial cells
A role for RAD001 in combination with Sandostatin LAR Depot in the treatment of advanced carcinoid tumor is suggested by data on the regulatory role of mTOR in cell growth and protein translation and the finding that somatostatin-induced growth arrest is mediated in part by inhibition of the PI3K pathway Charland et al 2001
The present study is designed to collect safetytolerability data and evidences for efficacy of RAD001 in the medically highly unmet indication of advanced pulmonary neuroendocrine tumor in Chinese patients
directly on the tumor cells by inhibiting tumor cell growth and proliferation
indirectly by inhibiting angiogenesis leading to reduced tumor vascularity via potent inhibition of tumor cell HIF-1 activity and VEGF production and VEGF-induced proliferation of endothelial cells
A role for RAD001 in combination with Sandostatin LAR Depot in the treatment of advanced carcinoid tumor is suggested by data on the regulatory role of mTOR in cell growth and protein translation and the finding that somatostatin-induced growth arrest is mediated in part by inhibition of the PI3K pathway Charland et al 2001
The present study is designed to collect safetytolerability data and evidences for efficacy of RAD001 in the medically highly unmet indication of advanced pulmonary neuroendocrine tumor in Chinese patients
Detailed Description:
The purpose of this phase I b study is to characterize the safety tolerability and efficacy of 10 mg RAD001 administered orally on a continuous once-daily dosing regimen in the treatment of advanced pulmonary neuroendocrine tumor The neuroendocrine tumors arising from bronchi and lung account for 30 of all carcinoid tumors and there are a lot of well differentiated adenocarcinoma squamous cancer and large cell lung cancer with significant neuroendocrine carcinoma characteristics who seems had a similarly prognosis with carcinoid tumor There is no effective treatment available for advanced pulmonary NETs at this time
The rationale for this study is based on both preclinical and clinical considerations IGF-1 is a known autocrine regulator of CgA secretion and cell growth in human neuroendocrine tumor cells von Wichert et al 2000 Wulbrand et al 2000 Van Gompel and Chen 2004 A role for RAD001 as monotherapy in carcinoid and pancreatic NET is suggested by the regulatory role of mTOR in cell growth metabolism and protein translation Fingar and Blenis 2004 Vignot et al 2005 and the Novartis observation that the PI3KmTOR pathway is activated by IGF-1 in carcinoid and pancreatic NET cells von Wichert et al 2000 Van Gompel and Chen 2004
The proposed RAD001 dosage regimen is 10 mgday in both monotherapy and combination therapy settings This regimen is based both on Novartis Phase III studies and on results from an investigator-sponsored study in NET Initial Phase I studies of the RAD001 10 mgday schedule demonstrated dose limiting toxicities in 2 of 12 patients Tolerability of this schedule was verified in a total of 33 patients in Phase 1 studies as well as in 12 breast cancer patients treated with letrozole 25 mg plus RAD001 10 mgday Pharmacodynamic modeling indicates that downstream effectors of mTOR are completely suppressed by RAD001 at the 10 mgday dose No increased toxicity is expected from use of RAD001 in combination with Sandostatin LAR Depot The investigator-sponsored study in NET toxicity observed with RAD001 5 mgday in combination with Sandostatin LAR Depot was similar to that observed for RAD001 5 mgday alone in Phase 1 studies Yao et al 2006 Therefore a dose of RAD001 10 mgday will be evaluated in this study
The rationale for this study is based on both preclinical and clinical considerations IGF-1 is a known autocrine regulator of CgA secretion and cell growth in human neuroendocrine tumor cells von Wichert et al 2000 Wulbrand et al 2000 Van Gompel and Chen 2004 A role for RAD001 as monotherapy in carcinoid and pancreatic NET is suggested by the regulatory role of mTOR in cell growth metabolism and protein translation Fingar and Blenis 2004 Vignot et al 2005 and the Novartis observation that the PI3KmTOR pathway is activated by IGF-1 in carcinoid and pancreatic NET cells von Wichert et al 2000 Van Gompel and Chen 2004
The proposed RAD001 dosage regimen is 10 mgday in both monotherapy and combination therapy settings This regimen is based both on Novartis Phase III studies and on results from an investigator-sponsored study in NET Initial Phase I studies of the RAD001 10 mgday schedule demonstrated dose limiting toxicities in 2 of 12 patients Tolerability of this schedule was verified in a total of 33 patients in Phase 1 studies as well as in 12 breast cancer patients treated with letrozole 25 mg plus RAD001 10 mgday Pharmacodynamic modeling indicates that downstream effectors of mTOR are completely suppressed by RAD001 at the 10 mgday dose No increased toxicity is expected from use of RAD001 in combination with Sandostatin LAR Depot The investigator-sponsored study in NET toxicity observed with RAD001 5 mgday in combination with Sandostatin LAR Depot was similar to that observed for RAD001 5 mgday alone in Phase 1 studies Yao et al 2006 Therefore a dose of RAD001 10 mgday will be evaluated in this study
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