Dosing and Effectiveness Study of Sorafenib and RAD001 in the Treatment of Patients With Advanced Kidney Cancer

Study Overview
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Brief Summary
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This study is being done in 2 parts. The first part is to determine the dose of RAD001 that should be used in combination with sorafenib. The second part is using the above determined dose of RAD001 in combination with sorafenib to see how effective these 2 drugs are against advanced kidney cancer. Participants will be asked to keep a pill diary.

Detailed Description
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The drugs used in this trial are called targeted drugs as they target specific activities that are carried out by cancer cells that make them grow and spread. Sorafenib is an approved drug for the treatment of advanced kidney cancer. RAD001 is an experimental drug that has been used in other research studies with other types of cancer. In this trial, the use of RAD001 and sorafenib together for the treatment of kidney cancer is experimental. In the Phase I portion of this study 13-16 patients will be treated with the same dose of sorafenib and different doses of RAD001. The purpose is to see what is a safe dose of RAD001 when combined with sorafenib in the treatment of kidney cancer. Once this dose of RAD001 is determined, about 65 more patients will be treated to see how effective this combination of drugs is against this kidney cancer. Both of these drugs are taken by mouth. Sorafenib will be taken twice a day. RAD001 is taken by mouth weekly. Patients will be able to continue treatment as long as their disease does not worsen or side effects become intolerable.

Official Title
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Phase I/II Trial of Sorafenib (Nexavar) and RAD001 (Everolimus)in the Treatment of Patients With Advanced Clear Cell Renal Cell Carcinoma

Conditions
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Kidney Cancer

Intervention / Treatment
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* Drug: Sorafenib
* Drug: RAD001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically documented metastatic or unresectable locally recurrent clear cell renal carcinoma Previous removal of kidney except if the size of the tumor was less than 5 cm or there was extensive liver or bone metastasis May have had no prior chemotherapy or up to 1 prior treatment regimen with immunotherapy or chemotherapy Performance status of 0-1 Measurable disease Adequate liver, renal, and bone marrow function Must be able to give written informed consent Women able to become pregnant must have a negative pregnancy test Must be 18 or over Must be able to swallow pills Exclusion Criteria: Prior treatment with sorafenib or m-TOR inhibitors History of acute MI within the last 6 months Active brain metastasis or patients with meningeal metastases Prior treatment for another cancer in the last 5 years Prior bleeding problems; coughing up or vomiting blood Non-healing wounds, ulcer, or long bone fracture Chronic use of systemic steroids or immunosuppressive agents Uncontrolled hypertension Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have. You can then decide if you wish to participate.

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: RAD001 and Sorafenib<br>RAD001 and Sorafenib | Drug: Sorafenib<br>* Sorafenib<br>* Other names: Nexavar;Drug: RAD001<br>* RAD001<br>* Other names: Everolimus, Zortress, Certican;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) of Patients Treated at MTD/Phase II Dose Level | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response Rate (ORR) = Percentage of Patients Who Experience an Objective Response (CR+ PR) to Treatment. In oncology, this outcome measure is reported for all patients treated at the same dose level and is not separated into Phase I and Phase II. The phase I and phase II results are not separated out as the timing of their enrollment (early in phase 1 or later phase II) is not relevant to the outcome measure. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival for Patients Treated at MTD/Phase II Dose Level | Progression is Defined Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% Increase in the Sum of the Longest Diameter of Target Lesions, or a Measurable Increase in a Non-target Lesion, or the Appearance of New Lesions. Progression-free survival was defined as the interval from the date of study entry until the date of tumor progression or death for the patients treated at the MTD/Phase II dose level. This outcome measure is reported for all patients treated at the same dose level and is not separated into Phase I and Phase II. The phase I and phase II results are not separated out as the timing of their enrollment (early in phase 1 or later phase II) is not relevant to the outcome measure. | 18 months |