Sorafenib in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors
This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Jennifer Chan, MD, MPH, Dana-Farber Cancer Institute
First received: July 17, 2009
Last updated: December 18, 2012
Last verified: December 2012
The purpose of this research study is to find out more about the combination of RAD001 and sorafenib such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating neuroendocrine tumors.
Pancreatic Neuroendocrine Tumor
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Phase I Study of Sorafenib in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors
Primary Outcome Measures:
- To determine the maximum tolerated dose (MTD) for sorafenib in combination with RAD001 in patients with advanced neuroendocrine tumors. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- To determine the dose-limiting toxicities of sorafenib combined with RAD001 in patients with advanced neuroendocrine tumors [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- To determine the safety and tolerability of the combination of sorafenib and RAD001 in patients with advanced neuroendocrine tumors. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- To make a preliminary assessment of the anti-tumor activity of the combination of sorafenib and RAD001 in patients with advanced neuroendocrine tumors. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Primary Completion Date:
||June 2013 (Final data collection date for primary outcome measure)
- Since we are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have neuroendocrine tumors, not everyone who participates in this research study will receive the same dose of the study drug. The dose the participant will be given will depend on the number of participants who have been enrolled in the study.
- Each treatment cycle lasts 28 days. Participants will take RAD001 orally once a day in the morning. Participants will take sorafenib orally twice daily.
- Initially participants will come to the clinic every other week. At these visits bloodwork will be taken to monitor the participants health. Every 2 months of treatment, participants will have a CT scan or MRI done to see how the medication is working.
- Participants will remain on this research study as long as they continue to benefit from the study medications.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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 lactating.
- 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 years.
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00942682
|Dana-Farber Cancer Institute
|Boston, Massachusetts, United States, 02115 |
Dana-Farber Cancer Institute
||Jennifer Chan, MD, MPH
||Dana-Farber Cancer Institute
No publications provided
||Jennifer Chan, MD, MPH, Principal Investigator, Dana-Farber Cancer Institute
History of Changes
|Other Study ID Numbers:
|Study First Received:
||July 17, 2009
||December 18, 2012
||United States: Institutional Review Board
Keywords provided by Dana-Farber Cancer Institute:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on May 16, 2013
Adenoma, Islet Cell
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Endocrine System Diseases