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

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Cancer
• Intervention / Treatment: Drug: Sorafenib; Drug: RAD001

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Marietta, Georgia, United States, 30060
      • Wellstar Cancer Research
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute
    • Louisville, Kentucky, United States, 40207
      • Baptist Hospital East
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Hematology Oncology Associates of Northern NJ
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
  • South Carolina
    • Columbia, South Carolina, United States, 29210
      • South Carolina Oncology Associates, PA
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Regional Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37023
      • Tennessee Oncology, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RAD001 and Sorafenib	Drug: Sorafenib; Sorafenib; Other Names: Nexavar; Drug: RAD001; RAD001; Other Names: Everolimus, Zortress, Certican

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: SCRI Development Innovations, LLC
• Collaborators: Bayer; Novartis
• Investigators: Principal Investigator: John D Hainsworth, MD, SCRI Development Innovations, LLC

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: October 25, 2006
• First Submitted That Met QC Criteria: October 25, 2006
• First Posted (Estimate): October 26, 2006

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: May 10, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Sorafenib; Everolimus
• Other Study ID Numbers: SCRI GU 44; CRAD001C2480