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RAD001 and Temozolomide in Patients With Advanced Pancreatic Neuroendocrine Tumors

Primary Purpose

Pancreatic Neuroendocrine Tumor

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

About this trial

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

Eligibility Criteria

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

Inclusion Criteria:

  • Locally unresectable or metastatic pancreatic neuroendocrine tumor
  • Radiologic, operative, or pathology reports should document a pancreatic location of tumor
  • Patients must have confirmed low-grade or intermediate-grade neuroendocrine carcinoma
  • Patients must have at least one measurable site of disease according to RECIST criteria that has not been preciously irradiated
  • 18 years of age or older
  • Minimum of two weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy
  • Prior treatment with chemotherapy is allowed, with the exception of prior treatment with temozolomide or dacarbazine
  • No Prior therapy with RAD001 or any other mTOR inhibitor
  • 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
  • Fasting serum cholesterol as outlined in protocol

Exclusion Criteria:

  • Prior treatment with any investigational drug within the preceding 4 weeks
  • 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
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
  • Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinoma of the skin
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  • Women who are pregnant or breast feeding
  • Patients who have received prior treatment with an mTOR inhibitor or temozolomide
  • Patients with known hypersensitivity to RAD001 or other rapamycins or to its excipients
  • History of noncompliance to medical regimens

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temozolomide with RAD001

Arm Description

Outcomes

Primary Outcome Measures

Response Rate
To determine the objective response rate by RECIST criteria of RAD001 in combination with temozolomide in patients with advanced pancreatic neuroendocrine tumors. Partial response (PR) by these criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Progressive disease (PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD) is defined as neither sufficient decrease to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started.

Secondary Outcome Measures

Progression-free Survival
To determine progression-free survival when RAD001 is given in combination with temozolomide in patients with advanced pancreatic neuroendocrine tumors. Progression-free survival is defined as time from start of therapy until disease progression, as defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, or death.
To Determine the Safety and Tolerability of This Drug Combination.
To determine the safety and tolerability of RAD001 when given in combination with temozolomide in patients with advanced pancreatic neuroendocrine tumors.

Full Information

First Posted
December 17, 2007
Last Updated
June 26, 2020
Sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Massachusetts General Hospital, Novartis, Schering-Plough
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1. Study Identification

Unique Protocol Identification Number
NCT00576680
Brief Title
RAD001 and Temozolomide in Patients With Advanced Pancreatic Neuroendocrine Tumors
Official Title
Phase I/II Study of RAD001 in Combination With Temozolomide in Patients With Advanced Pancreatic Neuroendocrine Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
March 29, 2019 (Actual)
Study Completion Date
March 29, 2019 (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, Schering-Plough

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This research study will test the safety of RAD001 in combination with temozolomide.
Detailed Description
Participants will take RAD001 by mouth daily. They will also take temozolomide by mouth daily for one week, followed by a one-week break period. This one-week on/one week off schedule for temozolomide will continue for the duration of the treatment. After the first month of treatment, there will be a 7-day observation period during which no study medication will be taken to observe for any side effects. During all treatment cycles (1 cycle is 28 days in length) participants will have a physical exam and will be asked questions about their general health and specific questions about any problems they may be experiencing. Initially, participants will come in every other week. At each of these visits, blood work will be taken to monitor the participants health. After every 2 months of treatment, participants will have a CT scan or MRI done to see how the medication is working.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Temozolomide with RAD001
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
RAD001
Intervention Description
Given orally once a day
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
Temodar
Intervention Description
Taken orally once a day for one week followed by a one-week break period
Primary Outcome Measure Information:
Title
Response Rate
Description
To determine the objective response rate by RECIST criteria of RAD001 in combination with temozolomide in patients with advanced pancreatic neuroendocrine tumors. Partial response (PR) by these criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Progressive disease (PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD) is defined as neither sufficient decrease to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
To determine progression-free survival when RAD001 is given in combination with temozolomide in patients with advanced pancreatic neuroendocrine tumors. Progression-free survival is defined as time from start of therapy until disease progression, as defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, or death.
Time Frame
2 years
Title
To Determine the Safety and Tolerability of This Drug Combination.
Description
To determine the safety and tolerability of RAD001 when given in combination with temozolomide in patients with advanced pancreatic 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 pancreatic neuroendocrine tumor Radiologic, operative, or pathology reports should document a pancreatic location of tumor Patients must have confirmed low-grade or intermediate-grade neuroendocrine carcinoma Patients must have at least one measurable site of disease according to RECIST criteria that has not been preciously irradiated 18 years of age or older Minimum of two weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy Prior treatment with chemotherapy is allowed, with the exception of prior treatment with temozolomide or dacarbazine No Prior therapy with RAD001 or any other mTOR inhibitor 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 Fasting serum cholesterol as outlined in protocol Exclusion Criteria: Prior treatment with any investigational drug within the preceding 4 weeks 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 Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinoma of the skin Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study Women who are pregnant or breast feeding Patients who have received prior treatment with an mTOR inhibitor or temozolomide Patients with known hypersensitivity to RAD001 or other rapamycins or to its excipients History of noncompliance to medical regimens
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Chan, MD, PhD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

Learn more about this trial

RAD001 and Temozolomide in Patients With Advanced Pancreatic Neuroendocrine Tumors

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