Ignite Creation Date:
2024-05-05 @ 10:38 PM
Last Modification Date:
2024-10-26 @ 10:21 AM
Study NCT ID:
NCT01152827
Status:
COMPLETED
Last Update Posted:
2015-05-20
First Post:
2010-05-31
Brief Title:
RAD001 in Pheochromocytoma or Nonfunctioning Carcinoid
Sponsor:
Seoul National University Hospital
Organization:
Seoul National University Hospital
Study Overview
Official Title:
Phase II Study of RAD001monotherapy in Patients With Unresectable Pheochromocytoma or Extra-adrenal Paraganglioma or Non-functioning Carcinoid
Status:
COMPLETED
Status Verified Date:
2010-06
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:
PheoCarcRAD001
Brief Summary:
According to Martin F et al AKT is highly phosphorylated in phenochromocytoma but not in benign adrenocortical tumors
In nonfunctioning carcinoid the PI3KAKTmTOR pathway is activated
Although mTOR is clearly an attractive therapeutic target in tumor no clinical study on mTOR inhibition by RAD001 have been conducted in pheochromocytoma or extra-adrenal paraganglioma or non-functioning carcinoid
So we design this phase II study of RAD001 in pheochromocytoma or extra-adrenal paraganglioma or non-functioning carcinoid to evaluate the efficacy of RAD001 in this orphan disease
In nonfunctioning carcinoid the PI3KAKTmTOR pathway is activated
Although mTOR is clearly an attractive therapeutic target in tumor no clinical study on mTOR inhibition by RAD001 have been conducted in pheochromocytoma or extra-adrenal paraganglioma or non-functioning carcinoid
So we design this phase II study of RAD001 in pheochromocytoma or extra-adrenal paraganglioma or non-functioning carcinoid to evaluate the efficacy of RAD001 in this orphan disease
Detailed Description:
Although several therapeutic options exist for patients with metastatic pheochromocytoma all options are limited and there is no cure Reduction of tumor size palliates symptoms but a survival advantage of debulking is unproven A reduced tumor burden can facilitate subsequent radiotherapy or chemotherapy External-beam irradiation of bone metastases and radio frequency ablation of lesions are treatment alternatives Chemotherapy with a combination of cyclophosphamide vincristin and dacarbazine can provide tumor regression and symptom relief in up to 50 of patients but the responses are usually short-lived To date 131I-labeled MIBG therapy is the single most valuable adjunct to surgical treatment of malignant pheochromocytomas As a single agent 131I-labeled MIBG has a limited efficacy of cure and there is no consensus on what doses to use for treating either bone or organ metastases Multicenter studies are required to reach a consensus on the efficacy of high-dose versus fractionated medium doses of 131I-labeled MIBG and monotherapy versus combination therapy with other radio nuclides or modes of chemotherapy
The PI3-KAktmTOR pathway is dysregulated in many cancers and is activated by several upstream proteins such as ras TCL1 and bcr-abl and membrane receptor tyrosine kinases including vascular endothelial growth factor receptor platelet-derived growth factor receptor c-kit and Flt3 Increased expression and constitutive activation of the catalytic subunit of PI3-K and Akt andor decreased or absent PTEN protein expression have been reported in many types of cancer Activating mutation in PIK3CA the gene for the catalytic subunit of PI3-K have been reported in 25 of gastric cancer
Upstream in the growth-promoting pathways that converge on mTOR are critical molecules that are often deregulated in cancer These deregulated molecules precede inappropriate signals that activate the mTOR switch driving the growth and proliferation of the cancer cell Because the number of potential defects that can cause inappropriate activation of mTOR is large and one or another is common to most cancer cells blocking their effect at the point of convergence is a rational approach
According to Martin F et al AKT is highly phosphorylated in phenochromocytoma but not in benign adrenocortical tumors
Although mTOR is clearly an attractive therapeutic target in tumor no clinical study on mTOR inhibition by RAD001 have been conducted in pheochromocytoma or extra-adrenal paraganglioma
So we conduct this phase II study of RAD001 in this disease And we also include the nonfunctioning carcinoid in this study
The PI3-KAktmTOR pathway is dysregulated in many cancers and is activated by several upstream proteins such as ras TCL1 and bcr-abl and membrane receptor tyrosine kinases including vascular endothelial growth factor receptor platelet-derived growth factor receptor c-kit and Flt3 Increased expression and constitutive activation of the catalytic subunit of PI3-K and Akt andor decreased or absent PTEN protein expression have been reported in many types of cancer Activating mutation in PIK3CA the gene for the catalytic subunit of PI3-K have been reported in 25 of gastric cancer
Upstream in the growth-promoting pathways that converge on mTOR are critical molecules that are often deregulated in cancer These deregulated molecules precede inappropriate signals that activate the mTOR switch driving the growth and proliferation of the cancer cell Because the number of potential defects that can cause inappropriate activation of mTOR is large and one or another is common to most cancer cells blocking their effect at the point of convergence is a rational approach
According to Martin F et al AKT is highly phosphorylated in phenochromocytoma but not in benign adrenocortical tumors
Although mTOR is clearly an attractive therapeutic target in tumor no clinical study on mTOR inhibition by RAD001 have been conducted in pheochromocytoma or extra-adrenal paraganglioma
So we conduct this phase II study of RAD001 in this disease And we also include the nonfunctioning carcinoid 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