RAD001 in Pheochromocytoma or Nonfunctioning Carcinoid

• Status: Completed
• Trial end date: 2011-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Seoul National University Hospital
• Treatments: Everolimus; Sirolimus

Criteria

Inclusion Criteria:

• 1. Histologically or cytologically confirmed pheochromocytoma or extra-adrenal paraganglioma or carcinoid

• 2. Local, locally-advanced or metastatic disease documented as having shown progression on a scan (CT, MRI, MIBI scan) taken 2 to 12 months prior to baseline compared to a previous scan taken at any time in the past. Progression must be documented according to RECIST criteria.

• 3. Disease that is not amenable to surgery, radiation or combined modality therapy with curative intent.

• 4. Presence of at least one measurable target lesion for further evaluation according to RECIST criteria

• 5. 18 years or older

• 6. ECOG performance status 0, 1

• 7. Previous treatment with chemotherapy, loco-regional therapy (e.g chemoembolization) are permitted providing that toxicity has resolved to ≤grade 1 at study entry and that last treatment was at least 4 weeks prior to baseline assessment.

• 8. Adequate organ function

• 9. A patient with the willingness to comply with the study protocol during the study period and capable of complying with it

• 10. A patient who signed the informed consent prior to the participation of the study and who understands that he/she has a right to withdrawal from participation in the study at any time without any disadvantages.

Exclusion Criteria:

• 1. A patient with no measurable disease

• 2. Prior chemotherapy, radiation therapy or surgery within 4 weeks prior to study entry except palliative radiotherapy to non-target lesions (within 2 weeks prior to study entry)

• 3. A patient with functioning carcinoid

• 4. A patient with previous active or passive immunotherapy

• 5. A patient with intestinal obstruction or impending obstruction, recent active upper GI bleeding

• 6. A pregnant or lactating patient

• 7. A patient of childbearing potential without being tested for pregnancy at baseline or with being tested for positive. (A postmenopausal woman with the amenorrhea period of at least 12 months or longer is considered to have non-childbearing potential)

• 8. A man or woman of childbearing potential who has no willingness to use a contraceptive measure during the study

• 9. A patient with history of another malignant disease within past 5 years, except curatively treated basal cell carcinoma of skin and cervical carcinoma in situ.

• 10. A patient with history of uncontrolled seizures, central nervous system disorder or psychiatric disorders that are considered clinically significant by the investigator that would prohibit the understanding of informed consent or that may be considered to interfere with the compliance of the administration of the study medications.

• 11. A patient with clinically significant heart disease (e.g. congestive heart failure, symptomatic coronary artery diseases, cardiac arrhythmia, etc) or myocardial infarction within past 12 months.

• 12. Ongoing cardiac arrhythmia of grade ≥2, atrial fibrillation of any grade, or QTc interval>450msec for males or >470msec for female.

• 13. A patient with interstitial pneumonia or diffuse symptomatic fibrosis of the lungs

• 14. A patient with peripheral neuropathy of grade 1 by NCI CTC, caused by other factors (e.g. alcohol, diabetes, etc). If the absence of deep tendon reflexes is the only neurologic disorder, this condition does not apply to the exclusion criteria.

• 15. A patient with organ transplantation requiring immunosuppressive therapy