Clinical Trial: RAD001 in Pheochromocytoma or Nonfunctioning Carcinoid

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase II Study of RAD001monotherapy in Patients With Unresectable Pheochromocytoma or Extra-adrenal Paraganglioma or Non-functioning Carcinoid

Brief Summary:

  • According to Martin F et al, AKT is highly phosphorylated in phenochromocytoma but not in benign adrenocortical tumors.
  • In nonfunctioning carcinoid, the PI3K/AKT/mTOR 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 Summary:

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-K/Akt/mTOR 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 and/or 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
Sponsor: Seoul National University Hospital

Current Primary Outcome: progression-free survival rate at 4 months [ Time Frame: 10 months ]

proportion of patients who are alive and progression-free at the time of 4 months of treatment among all patients


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • time to progression (TTP) [ Time Frame: 10 months ]
  • overall survival (OS) [ Time Frame: 2 years ]
  • response rate (RR) [ Time Frame: 6 months ]
  • metabolic response rate by PET-CT [ Time Frame: 2 months ]


Original Secondary Outcome: Same as current

Information By: Seoul National University Hospital

Dates:
Date Received: May 31, 2010
Date Started: July 2008
Date Completion:
Last Updated: May 19, 2015
Last Verified: June 2010