Sorafenib in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors

Sponsor

Dana-Farber Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00942682

Collaborator

Novartis (Industry), Bayer (Industry)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neuroendocrine Tumor Carcinoid Tumor Pancreatic Neuroendocrine Tumor	Drug: Sorafenib Drug: RAD001	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Study of Sorafenib in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sorafenib and RAD001 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. Participants will remain on this research study as long as they continue to benefit from the study medications.	Drug: Sorafenib Taken orally twice daily Drug: RAD001 Taken orally once daily in the morning

Arm

Intervention/Treatment

Experimental: Sorafenib and RAD001

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. Participants will remain on this research study as long as they continue to benefit from the study medications.

Drug: Sorafenib

Taken orally twice daily

Drug: RAD001

Taken orally once daily in the morning

Outcome Measures

Primary Outcome Measures

To determine the maximum tolerated dose (MTD) for sorafenib in combination with RAD001 in patients with advanced neuroendocrine tumors. [2 years]
To determine the dose-limiting toxicities of sorafenib combined with RAD001 in patients with advanced neuroendocrine tumors [2 years]

Secondary Outcome Measures

To determine the safety and tolerability of the combination of sorafenib and RAD001 in patients with advanced neuroendocrine tumors. [2 years]
To make a preliminary assessment of the anti-tumor activity of the combination of sorafenib and RAD001 in patients with advanced neuroendocrine tumors. [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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