RAD001 and Temozolomide in Patients With Advanced Pancreatic Neuroendocrine Tumors

Study Overview
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Brief Summary
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This research study will test the safety of RAD001 in combination with temozolomide.

Detailed Description
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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.

Official Title
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Phase I/II Study of RAD001 in Combination With Temozolomide in Patients With Advanced Pancreatic Neuroendocrine Tumors

Conditions
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Pancreatic Neuroendocrine Tumor

Intervention / Treatment
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* Drug: RAD001
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temozolomide with RAD001<br> | Drug: RAD001<br>* Given orally once a day<br>Drug: Temozolomide<br>* Taken orally once a day for one week followed by a one-week break period<br>* Other names: Temodar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 years | 
| 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. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RAD001, temozolomide