Pasireotide in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Massachusetts General Hospital
Novartis
Information provided by (Responsible Party):
Jennifer Chan, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00804336
First received: December 5, 2008
Last updated: December 18, 2012
Last verified: December 2012
  Purpose

The purpose of this research study is to determine the safety of the combination of SOM230 and RAD001, as well as determine the highest dose of this combination that can be given to people safely. SOM230 is an investigational drug that is similar to Sandostatin LAR. Sandostatin is an approved drug for the use of treating symptoms of neuroendocrine tumors. SOM230 has shown to be effective in patients who have become resistant to Sandostatin and may also stop cancer cells from growing. RAD001 is an investigational drug that also may stop cancer cells from growing.


Condition Intervention Phase
Neuroendocrine Tumor
Carcinoid Tumor
Pancreatic Neuroendocrine Tumor
Drug: SOM230
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 Pasireotide (SOM230) 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 for pasireotide (SOM230) in combination with RAD001 in this patient population. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To determine the dose-limiting toxicities of the combination in this patient population. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the pharmacokinetics of combined treatment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To make a preliminary assessment of the anti-tumor activity of the combination in this patient population [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To determine the objective response rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To determine the duration of response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To determine the progression free survival and overall survival of patients receiving this combination. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: October 2008
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: SOM230
    Given subcutaneously twice a day for four weeks then given intramuscularly once every four weeks thereafter
    Other Name: pasireotide
    Drug: RAD001
    Given orally once a day
Detailed Description:
  • Participants will be receiving two study medications, SOM230 and RAD001, during each treatment cycle. Each treatment cycle lasts 4 weeks.
  • For the first four weeks of treatment, the participant will self-administer the SOM230 twice a day by subcutaneous injection. If they tolerate the SOM230 after 4 weeks, they will switched to the long-acting SOM230 which will be administered during scheduled treatment visits once every 4 weeks. For the first two weeks after switching to the long-acting SOM230, participants will continue to self-administer the short-acting SOM230 twice a day.
  • RAD001 will be taken orally once every day.
  • On Day 1 of every cycle, a physical exam and blood tests will be performed. Following every 2 cycles of treatment an assessment of the tumor by CT scan wil be performed.
  • Pharmacokinetic (pK) blood samples will be taken on days 1 and 15 of cycle one. The pK samples will be taken right before the study drug is administered and then 1, 2, 3, and 5 hours later.
  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. 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, of completion of all prior systemic anticancer therapy.
  • ECOG Performance Status 0,1, or 2.
  • Life expectancy 12 weeks or more.
  • Adequate bone marrow, liver and renal function as outlined in the protocol
  • Negative serum pregnancy test for women of childbearing potential.
  • Fasting serum cholesterol less than or equal to 300mg/dL or less than or equal to 7.75mml/L AND fasting triglycerides of less than or equal to 2.5 x ULN.

Exclusion Criteria:

  • Chronic treatment with systemic steroids or another immunosuppressive agent.
  • Immunization with attenuated live vaccines during study or within 1 week of study entry.
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
  • 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.
  • Uncontrolled diabetes mellitus or a fasting plasma glucose of > 1.5 ULN.
  • Symptomatic cholelithiasis
  • Congestive heart failure, 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.
  • Presence of active or suspected acute or chronic uncontrolled infection or with a history of immunocompromise, including a positive HIV test result.
  • Any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study such as: severely impaired lung function; active or uncontrolled infection/disorders; nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by treatment with the study therapy; impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001; history of alcohol or drug abuse in the 6 month period prior to receiving treatment.
  • Known hypersensitivity to RAD001 or other rapamycins or its excipients.
  • Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide LAR or s.c. formulations.
  • History of non-compliance to medical regimens.
  • Patients taking medication known to inhibit, induce, or be a substrate to isoenzyme CYP3A.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00804336

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02214
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Massachusetts General Hospital
Novartis
Investigators
Principal Investigator: Jennifer Ang Chan, MD, MPH Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Jennifer Chan, MD, MPH, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00804336     History of Changes
Other Study ID Numbers: 08-087
Study First Received: December 5, 2008
Last Updated: December 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
pasireotide
SOM230
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
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 22, 2014