Pancreatic Cancer
Conditions
Keywords
RAD001, metastatic pancreatic cancer
Brief summary
The purpose of this research study is to investigate if RAD001 is an effective treatment for pancreatic cancer that has spread and not responded to treatment. Experiments have shown that RAD001 can prevent cells from multiplying. RAD002 has also been tested in laboratory experiments imitating cancer conditions and the results have been promising.
Detailed description
* Participants taking part in this research study will be given a study medication-dosing calendar for each treatment cycle. Each cycle lasts four weeks during which you will be taking the study drug, RAD001, orally every day. * Participants will come into the clinic every other week during the time of enrollment. At each clinic visit blood work will be taken to monitor the participants health and a physical exam will be performed. CT scans will be repeated every 2 months to assess the tumor. * Participants will remain on the study as long as they continue to benefit from the study medication.
Interventions
DRUGRAD001
Taken orally daily for as long as the participant continues to receive a benefit.
Sponsors
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Novartis
Dana-Farber Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologic confirmation of pancreatic adenocarcinoma * 18 years of age or older * At least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. * Treated with gemcitabine-based chemotherapy with documented tumor progression on gemcitabine or intolerance to gemcitabine. * Prior treatment with no more than 1 prior chemotherapy regimen for metastatic disease. * Minimum of two weeks since any major surgery, completion of radiation, or completion of all prior systemic anti-cancer therapy. * ECOG performance status 0-1. * Life expectancy of greater than 12 weeks. * Adequate bone marrow and liver function. * Must be able to swallow tablets.
Exclusion criteria
* Prior treatment with an investigational drug within the preceding 4 weeks. * Prior treatment with an inhibitor of mTOR * Chronic treatment with systemic steroids or another immunosuppressive agent * More than one prior chemotherapy treatment for metastatic disease * Uncontrolled brain or leptomeningeal metastases, including patient 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 carcinomas of the skin * Patients with chronic renal insufficiency * Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study. * Known history of HIV seropositivity * Impairment of gastrointestinal function or gastrointestinal disease that my significantly alter the absorption of RAD001. * Active, bleeding diathesis or an oral vitamin K antagonist medication * Women who are pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Assess Progression-free Survival of RAD001 at Two Months in Patients With Metastatic Pancreatic Cancer Whose Disease Has Progressed on Gemcitabine Chemotherapy. | two months | The Outcome Measure is reporting the number of participants experiencing Progression-free Survival at 2 months after treatment. The study was designed with a primary end point of progression-free survival (PFS), defined as the time from study entry to documentation of progressive disease or death from any cause. On the basis of prior studies of second-line treatment in metastatic pancreatic cancer, we estimated that such treatment has been associated with a median PFS of 2 months. Our study design used a one-stage design with a target accrual of 35 eligible patients, with the assumption that an improvement in PFS at 2 months from 50% to 71% would warrant further study in this patient population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Safety of RAD001 in Patients With Metastatic Pancreatic Cancer | Patients were followed for the duration of their time on treatment and 30 days after their last dose of RAD001. | Patients were followed for the duration of their time on treatment and 30 days after their last dose of RAD001. The number of patients with treatment-related adverse events are reported. |
| to Assess Response Rate Associated With RAD001 in This Patient Population. | 2 years | The secondary objectives of the study were to assess tumor response rate and overall survival. Patients were required to have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST). Per RECIST, for target lesions assessed by CT: Complete Response (CR) is Disappearance of all target lesions; Partial Response (PR) is \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) equals CR + PR. |
| to Assess Overall Survival Associated With RAD001 in This Patient Population. | 2 years | Overall survival was defined as the time from study entry until death from any cause. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RAD001 RAD001: Taken orally daily for as long as the participant continues to receive a benefit. | 33 |
| Total | 33 |
Baseline characteristics
| Characteristic | RAD001 |
|---|---|
| Age, Customized | 61 years |
| Region of Enrollment United States | 33 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 33 / 33 |
| serious Total, serious adverse events | 25 / 33 |
Outcome results
Primary
To Assess Progression-free Survival of RAD001 at Two Months in Patients With Metastatic Pancreatic Cancer Whose Disease Has Progressed on Gemcitabine Chemotherapy.
The Outcome Measure is reporting the number of participants experiencing Progression-free Survival at 2 months after treatment. The study was designed with a primary end point of progression-free survival (PFS), defined as the time from study entry to documentation of progressive disease or death from any cause. On the basis of prior studies of second-line treatment in metastatic pancreatic cancer, we estimated that such treatment has been associated with a median PFS of 2 months. Our study design used a one-stage design with a target accrual of 35 eligible patients, with the assumption that an improvement in PFS at 2 months from 50% to 71% would warrant further study in this patient population.
Time frame: two months
Population: On the basis of prior studies of 2nd line treatment in metastatic pancreatic cancer, we estimated a median PFS of 2 months. Our study design used a one-stage design with a target accrual of 35 eligible patients, with the assumption that an improvement in PFS at 2 months from 50% to 71% would warrant further study in this population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RAD001 | To Assess Progression-free Survival of RAD001 at Two Months in Patients With Metastatic Pancreatic Cancer Whose Disease Has Progressed on Gemcitabine Chemotherapy. | 23 participants |
p-value: 0.1binomial hypothesis test
Secondary
to Assess Overall Survival Associated With RAD001 in This Patient Population.
Overall survival was defined as the time from study entry until death from any cause.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RAD001 | to Assess Overall Survival Associated With RAD001 in This Patient Population. | 4.5 months |
Secondary
to Assess Response Rate Associated With RAD001 in This Patient Population.
The secondary objectives of the study were to assess tumor response rate and overall survival. Patients were required to have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST). Per RECIST, for target lesions assessed by CT: Complete Response (CR) is Disappearance of all target lesions; Partial Response (PR) is \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) equals CR + PR.
Time frame: 2 years
Population: Of the 33 patients enrolled, 29 reached restaging. Three patients who did not reach restaging were removed from study because of withdrawal of consent. One patient was removed from study after 8 days of treatment because of worsening of a preexisting perirectal fistula, requiring surgical intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RAD001 | to Assess Response Rate Associated With RAD001 in This Patient Population. | Stable Disease as Best Response | 7 participants |
| RAD001 | to Assess Response Rate Associated With RAD001 in This Patient Population. | Progressive Disease as Best Response | 22 participants |
Secondary
To Assess the Safety of RAD001 in Patients With Metastatic Pancreatic Cancer
Patients were followed for the duration of their time on treatment and 30 days after their last dose of RAD001. The number of patients with treatment-related adverse events are reported.
Time frame: Patients were followed for the duration of their time on treatment and 30 days after their last dose of RAD001.
Population: A total of 33 eligible patients received at least 1 week of study drug and are included in our toxicity analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RAD001 | To Assess the Safety of RAD001 in Patients With Metastatic Pancreatic Cancer | 33 participants |