Pancreatic Neuroendocrine Tumor
Conditions
Keywords
RAD001, temozolomide
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.
Interventions
DRUGRAD001
Given orally once a day
DRUGTemozolomide
Taken orally once a day for one week followed by a one-week break period
Sponsors
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Massachusetts General Hospital
Novartis
Schering-Plough
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 2 years | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 2 years | 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. | 2 years | To determine the safety and tolerability of RAD001 when given in combination with temozolomide in patients with advanced pancreatic neuroendocrine tumors. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Temozolomide and Everolimus Temozolomide was administered to all patients at a starting dose of 150 mg/m2 on days 1 to 7 and days 15 to 21 of a 28-day cycle. Everolimus was administered together with temozolomide in 2 dose cohorts: 1) 5 mg daily and 2) 10 mg daily. | 43 |
| Total | 43 |
Baseline characteristics
| Characteristic | Temozolomide and Everolimus | — |
|---|---|---|
| Age, Continuous | 53 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 17 Participants | — |
| Sex: Female, Male Male | 26 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 43 |
| other Total, other adverse events | 43 / 43 |
| serious Total, serious adverse events | 15 / 43 |
Outcome results
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Temozolomide and Everolimus | Response Rate | 16 Participants |
Secondary
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.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Temozolomide and Everolimus | Progression-free Survival | 15.4 months |
Secondary
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.
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Temozolomide and Everolimus | To Determine the Safety and Tolerability of This Drug Combination. | Grade 3 or 4 thrombocytopenia | 7 Participants |
| Temozolomide and Everolimus | To Determine the Safety and Tolerability of This Drug Combination. | Grade 3 or 4 mucositis | 1 Participants |
| Temozolomide and Everolimus | To Determine the Safety and Tolerability of This Drug Combination. | Grade 3 or 4 hyperglycemia | 8 Participants |
| Temozolomide and Everolimus | To Determine the Safety and Tolerability of This Drug Combination. | Grade 3 or 4 Lymphopenia | 19 Participants |
| Temozolomide and Everolimus | To Determine the Safety and Tolerability of This Drug Combination. | Grade 3 or 4 AST Increase | 4 Participants |
| Temozolomide and Everolimus | To Determine the Safety and Tolerability of This Drug Combination. | Grade 3 or 4 Leukocyte decrease | 7 Participants |