Phase I Study of Everolimus (RAD001) in Combination With Lenalidomide in Patients With Advanced Solid Malignancies Enriched for Renal Cell Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- Lenalidomide
- Conditions
- Solid Organ Malignancies
- Sponsor
- Emory University
- Enrollment
- 44
- Locations
- 2
- Primary Endpoint
- Number of Participants With Dose Limiting Toxicities (DLT) at Each Dose Level
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Investigators
Taofeek K. Owonikoko
Professor and Principal Investigator
Emory University
Eligibility Criteria
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.
Exclusion Criteria
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements including signing the informed consent form.
- •Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
- •Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- •Use of any other experimental drug or therapy within 28 days of baseline.
- •Known hypersensitivity to thalidomide or everolimus (including other rapamycins, sirolimus and temsirolimus).
- •The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- •Prior treatment with lenalidomide or everolimus.
- •Concurrent use of other anti-cancer agents or treatments.
- •Patients known to be positive for HIV or infectious hepatitis, type B or C requiring active therapy. Patients on combination antiviral therapy are ineligible because of the potential for pharmacokinetic interactions with everolimus and or lenalidomide. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in this patient population.
- •Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
Arms & Interventions
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.
Intervention: Lenalidomide
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.
Intervention: Everolimus
Outcomes
Primary Outcomes
Number of Participants With Dose Limiting Toxicities (DLT) at Each Dose Level
Time Frame: 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.