Sorafenib in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors

This study has been completed.
Sponsor:
Collaborators:
Novartis
Bayer
Information provided by (Responsible Party):
Jennifer Chan, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00942682
First received: July 17, 2009
Last updated: April 27, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Neuroendocrine Tumor
Carcinoid Tumor
Pancreatic Neuroendocrine Tumor
Drug: Sorafenib
Drug: RAD001
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Sorafenib in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

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 ]

Enrollment: 21
Study Start Date: July 2009
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00942682

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Novartis
Bayer
Investigators
Principal Investigator: Jennifer Chan, MD, MPH Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: Jennifer Chan, MD, MPH, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00942682     History of Changes
Other Study ID Numbers: 09-094
Study First Received: July 17, 2009
Last Updated: April 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
sorafenib
RAD001

Additional relevant MeSH terms:
Carcinoid Tumor
Neuroendocrine Tumors
Adenoma, Islet Cell
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Adenoma
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Sirolimus
Everolimus
Sorafenib
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 24, 2014