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Sorafenib in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors

Primary Purpose

Neuroendocrine Tumor, Carcinoid Tumor, Pancreatic Neuroendocrine Tumor

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Sorafenib
RAD001
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroendocrine Tumor focused on measuring sorafenib, RAD001

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sorafenib and RAD001

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
July 17, 2009
Last Updated
April 27, 2014
Sponsor
Dana-Farber Cancer Institute
Collaborators
Novartis, Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT00942682
Brief Title
Sorafenib in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors
Official Title
Phase I Study of Sorafenib in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Novartis, Bayer

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroendocrine Tumor, Carcinoid Tumor, Pancreatic Neuroendocrine Tumor
Keywords
sorafenib, RAD001

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sorafenib and RAD001
Arm Type
Experimental
Arm 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. Participants will remain on this research study as long as they continue to benefit from the study medications.
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Intervention Description
Taken orally twice daily
Intervention Type
Drug
Intervention Name(s)
RAD001
Intervention Description
Taken orally once daily in the morning
Primary Outcome Measure Information:
Title
To determine the maximum tolerated dose (MTD) for sorafenib in combination with RAD001 in patients with advanced neuroendocrine tumors.
Time Frame
2 years
Title
To determine the dose-limiting toxicities of sorafenib combined with RAD001 in patients with advanced neuroendocrine tumors
Time Frame
2 years
Secondary Outcome Measure Information:
Title
To determine the safety and tolerability of the combination of sorafenib and RAD001 in patients with advanced neuroendocrine tumors.
Time Frame
2 years
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Chan, MD, MPH
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23475104
Citation
Chan JA, Mayer RJ, Jackson N, Malinowski P, Regan E, Kulke MH. Phase I study of sorafenib in combination with everolimus (RAD001) in patients with advanced neuroendocrine tumors. Cancer Chemother Pharmacol. 2013 May;71(5):1241-6. doi: 10.1007/s00280-013-2118-9. Epub 2013 Mar 9.
Results Reference
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Sorafenib in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors

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