Adenoidcystic Carcinoma, Neuroendocrine Tumors, Solid Organ Malignancies
Conditions
Keywords
kidney cancer, adenoidcystic cancer
Brief summary
The purpose of this study is to study the combination of two anticancer drugs, everolimus (RAD001) and lenalidomide in patients whose cancer is no longer responding to standard treatment or patients who are unable to tolerate the standard treatment for their cancer.
Detailed description
The purpose of this study is to study the combination of two anticancer drugs, everolimus (RAD001) and lenalidomide in patients whose cancer is no longer responding to standard treatment or patients who are unable to tolerate the standard treatment for their cancer. The investigators seek to establish the safety of taking these two medications together and to determine the appropriate doses of the two drugs when given together as well as identify potential side effects when the drugs are administered together. Another purpose of this study is to find out if the medication works for the patient's kind of cancer and side effects of the combination of RAD001 and lenalidomide by looking at the patient's response to the treatment. The investigators want to find out what effects, good or bad, the drugs have on the patient's cancer. This study will also look at specific substances called biomarkers in the patient's blood and in the tumor tissue which are involved in the growth of tumor cells and determine if the levels of these biomarkers are related to the patient's response to treatment or development of side effects. An expansion cohort is currently enrolling patients with adenoidcystic carcinoma, neuroendocrine and kidney cancer.
Interventions
DRUGLenalidomide
Lenalidomide (10mg, 15mg, 20mg or 25mg) once daily by mouth, every day of each 28-day cycle.
DRUGEverolimus
5mg or 10mg of everolimus administered once daily by mouth on a once daily continuous dosing schedule for 28 days.
Sponsors
Celgene
Novartis
Emory University
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
* Subjects must meet the following inclusion/
Exclusion criteria
to be eligible for the study. * Ability to understand and willingness to voluntarily sign an informed consent form. * Histologic or cytologic confirmation of a solid malignancy. * Age ≥ 18 years at the time of signing the informed consent form. Because no dosing or adverse event data are currently available on the use of everolimus in combination with lenalidomide in patients \< 18 years of age, children are excluded from this study. * Able to adhere to the study visit schedule and other protocol requirements. * Patients must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. * Diagnosed with advanced refractory solid malignancies or intolerant of standard therapy for the stage of the disease (because there is currently no standard approved therapy for adenoidcystic carcinoma, therefore there is no requirement of prior therapy for this patient population). * All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study. A minimum of 6 weeks treatment break is required in case of nitrosoureas or mitomycin C. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 at study entry. * Able to receive prophylactic anticoagulation with aspirin, warfarin or low molecular weight heparin when required for lenalidomide administration. * Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x upper limit of normal (ULN). NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. * Laboratory test results within these ranges: * Absolute neutrophil count 1500 ≥ /mm³ * Platelet count ≥ 100,000/mm³ * Hb ≥ 9 g/dL * Creatinine within institutional limits of normal or creatinine clearance ≥ 60 ml/min/m² if elevated creatinine * Total bilirubin \< 2.0 mg/dL or \< 1.5.0 x ULN for the institution whichever is higher * Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) \< 2.x ULN or \< 5 x ULN if hepatic metastases are present. * All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS®) program, and be willing and able to comply with the requirements of the REMS® program. * Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. * Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-International Unit (mIU)/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLT) at Each Dose Level | Within the first 28 days for DLT and throughout the duration of the study for safety. | A standard 3 + 3 design was employed to study escalating doses of daily, orally administered lenalidomide and everolimus. Dose escalation to the next cohort required 0 of 3 or ≤1 of 6 patients with dose-limiting toxicity (DLT). Five dose cohorts were planned starting at dose level one with lenalidomide 10 mg and everolimus 5mg in a 28-day cycle up to maximum doses of 25 and 10 mg, respectively. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide Combination With Everolimus Non-randomized study of escalating doses of daily, orally administered lenalidomide in combination with standard doses of everolimus, an orally available mammalian target of rapamycin (mTOR) inhibitor.
Lenalidomide: Lenalidomide (10mg, 15mg, 20mg or 25mg) once daily by mouth, every day of each 28-day cycle.
Everolimus: 5mg or 10mg of everolimus administered once daily by mouth on a once daily continuous dosing schedule for 28 days. | 44 |
| Total | 44 |
Baseline characteristics
| Characteristic | Lenalidomide Combination With Everolimus |
|---|---|
| Age, Continuous | 58 Years STANDARD_DEVIATION 44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 32 Participants |
| Region of Enrollment United States | 44 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 18 / 44 |
| other Total, other adverse events | 38 / 44 |
| serious Total, serious adverse events | 18 / 44 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLT) at Each Dose Level
A standard 3 + 3 design was employed to study escalating doses of daily, orally administered lenalidomide and everolimus. Dose escalation to the next cohort required 0 of 3 or ≤1 of 6 patients with dose-limiting toxicity (DLT). Five dose cohorts were planned starting at dose level one with lenalidomide 10 mg and everolimus 5mg in a 28-day cycle up to maximum doses of 25 and 10 mg, respectively.
Time frame: Within the first 28 days for DLT and throughout the duration of the study for safety.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lenalidomide Combination With Everolimus | Number of Participants With Dose Limiting Toxicities (DLT) at Each Dose Level | Lenalidomide/everolimus (10/5 mg) | 3 Participants |
| Lenalidomide Combination With Everolimus | Number of Participants With Dose Limiting Toxicities (DLT) at Each Dose Level | Lenalidomide/everolimus(15/5 mg) | 3 Participants |
| Lenalidomide Combination With Everolimus | Number of Participants With Dose Limiting Toxicities (DLT) at Each Dose Level | Lenalidomide/everolimus(20/5 mg) | 5 Participants |
| Lenalidomide Combination With Everolimus | Number of Participants With Dose Limiting Toxicities (DLT) at Each Dose Level | Lenalidomide/everolimus(25/5 mg) | 3 Participants |
| Lenalidomide Combination With Everolimus | Number of Participants With Dose Limiting Toxicities (DLT) at Each Dose Level | Lenalidomide/everolimus(25/10 mg) | 8 Participants |
| Lenalidomide Combination With Everolimus | Number of Participants With Dose Limiting Toxicities (DLT) at Each Dose Level | Recommended Phase 2Dose: L (25mg) and E (10mg) | 22 Participants |