Phase I Study of Sorafenib in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors
- Locally unresectable or metastatic neuroendocrine tumor (carcinoid tumor or
pancreatic neuroendocrine tumor). Patients must have confirmed low-grade or
intermediate-grade neuroendocrine carcinoma. Patients with poorly differentiated
neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet
cell carcinoid, and small cell carcinoma are not eligible.
- 18 years of age or older
- Minimum of four weeks since any major surgery, completion of radiation, or completion
of all prior systemic anticancer therapy. Bevacizumab should not have been received
within the prior 6 weeks.
- Prior treatment with chemotherapy is allowed. Patients may not have received prior
therapy with RAD001 or sorafenib. There is no limit to the number of prior
chemotherapy regimens a patient may have received. Patients may receive concomitant
therapy with somatostatin analogs.
- ECOG performance status 0 or 1
- Life expectancy 12 weeks or more
- Adequate bone marrow, liver and renal function as outlined in the protocol
- Fasting serum glycerides and fasting triglycerides as outlined in the protocol
- INR < 1.5 or PT/PTT within normal limits. Patients receiving anti-coagulation
treatment with an agent such as warfarin or heparin may be allowed to participate.
- Women of child bearing potential must have a negative serum pregnancy test within 14
days of the administration of the first study treatment. Women must not be
- Prior treatment with cytotoxic chemotherapy, radiation, immunotherapy, or any
investigational drug within the preceding 4 weeks. Bevacizumab should not have been
received within the prior 6 weeks.
- Prior treatment with RAD001 or sorafenib
- Patients who have undergone major surgery within 4 weeks prior to study enrollment.
- Chronic treatment with systemic steroids or another immunosuppressive agent
- Patients should not receive immunization with attenuated live vaccines during study
period or within 1 week of study entry.
- Known brain metastases
- Patients with prior or concurrent malignancy except for the following: adequately
treated basal cell or squamous cell skin cancer, or other adequately treated in situ
cancer, or any other cancer from which the patient has been disease free for five
- Patients with uncontrolled diabetes mellitis or a fasting plasma glucose > 1.5 ULN
- Patients who have congestive heart failure (NHYA Class III or IV), unstable angina,
sustained ventricular tachycardia, ventricular fibrillation, clinically significant
bradycardia, advanced heart block or a history of acute myocardial infarction within
the six months preceding enrollment. No new onset angina within 3 months preceding
enrollment. No cardiac ventricular arrhythmia requiring antiarrhythmic therapy.
- Uncontrolled hypertension
- Active clinically serious infection
- Serious non-healing wound, ulcer, or bone fracture
- Evidence of history of bleeding diathesis or coagulopathy
- Patients with the presence of active or suspected acute or chronic uncontrolled
infection or with a history of immunocompromise, including a positive HIV test result
- Patients who have any severe and/or uncontrolled medical conditions or other
conditions what could affect their participation in the study
- Use of St. John's Wort or rifampin (rifampicin)
- Patients with a known or suspected hypersensitivity to sorafenib, RAD001 or other
rapamycins or to its excipients