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Pasireotide 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
SOM230
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 pasireotide, SOM230, RAD001

Eligibility Criteria

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

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.

Sites / Locations

  • Beth Israel Deaconess Medical Center
  • Dana-Farber Cancer Institute
  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pasireotide and RAD001

Arm Description

RAD001 was administered orally as a once-daily dose. Pasireotide s.c. was self-administered s.c. twice daily for 4 weeks. If pasireotide s.c. was tolerated, patients received pasireotide LAR i.m. at the corresponding dose level. Pasireotide s.c. was continued for an additional 2 weeks after administration of pasireotide LAR until anticipated steady-state levels of pasireotide LAR were achieved. Pasireotide LAR was administered every 28 days. Cycles for everolimus and pasireotide LAR were repeated every 28 days.

Outcomes

Primary Outcome Measures

To determine the maximum tolerated dose for pasireotide (SOM230) in combination with RAD001 in this patient population.
To determine the dose-limiting toxicities of the combination in this patient population.

Secondary Outcome Measures

To determine the pharmacokinetics of combined treatment
To make a preliminary assessment of the anti-tumor activity of the combination in this patient population
To determine the objective response rate
To determine the duration of response
To determine the progression free survival and overall survival of patients receiving this combination.

Full Information

First Posted
December 5, 2008
Last Updated
October 18, 2016
Sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Massachusetts General Hospital, Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00804336
Brief Title
Pasireotide in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors
Official Title
Phase I Study of Pasireotide (SOM230) in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Massachusetts General Hospital, Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

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
pasireotide, SOM230, 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
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pasireotide and RAD001
Arm Type
Experimental
Arm Description
RAD001 was administered orally as a once-daily dose. Pasireotide s.c. was self-administered s.c. twice daily for 4 weeks. If pasireotide s.c. was tolerated, patients received pasireotide LAR i.m. at the corresponding dose level. Pasireotide s.c. was continued for an additional 2 weeks after administration of pasireotide LAR until anticipated steady-state levels of pasireotide LAR were achieved. Pasireotide LAR was administered every 28 days. Cycles for everolimus and pasireotide LAR were repeated every 28 days.
Intervention Type
Drug
Intervention Name(s)
SOM230
Other Intervention Name(s)
pasireotide
Intervention Description
Given subcutaneously twice a day for four weeks then given intramuscularly once every four weeks thereafter
Intervention Type
Drug
Intervention Name(s)
RAD001
Intervention Description
Given orally once a day
Primary Outcome Measure Information:
Title
To determine the maximum tolerated dose for pasireotide (SOM230) in combination with RAD001 in this patient population.
Time Frame
2 years
Title
To determine the dose-limiting toxicities of the combination in this patient population.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
To determine the pharmacokinetics of combined treatment
Time Frame
2 years
Title
To make a preliminary assessment of the anti-tumor activity of the combination in this patient population
Time Frame
2 years
Title
To determine the objective response rate
Time Frame
3 years
Title
To determine the duration of response
Time Frame
3 years
Title
To determine the progression free survival and overall survival of patients receiving this combination.
Time Frame
5 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Ang Chan, MD, MPH
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02214
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22736724
Citation
Chan JA, Ryan DP, Zhu AX, Abrams TA, Wolpin BM, Malinowski P, Regan EM, Fuchs CS, Kulke MH. Phase I study of pasireotide (SOM 230) and everolimus (RAD001) in advanced neuroendocrine tumors. Endocr Relat Cancer. 2012 Sep 14;19(5):615-23. doi: 10.1530/ERC-11-0382. Print 2012 Oct.
Results Reference
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Pasireotide in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors

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