Velcade and Sorafenib in Unresected or Metastatic Renal Cell Carcinoma
This is an open label, non-randomized, single arm phase II study. The primary objective of this study is to investigate the efficacy of combination of sorafenib and VELCADE® (bortezomib). The primary efficacy endpoint is Progression-Free Survival (PFS). The secondary objectives of this study are to:
Assess the response rate of this combination in this patient population and Assess the toxicity of this combination in this patient population
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Velcade (Bortezomib) and Sorafenib in Unresected or Metastatic Renal Cell Carcinoma|
- Progression Free Survival (PFS) [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]Progression free survival will be measured from the beginning of treatment until there is evidence of progressive disease or death from any cause. Progression is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI): Progressive Disease (PD), 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.
- Overall Response Rate (ORR) [ Time Frame: 42 days ] [ Designated as safety issue: No ]Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI:) 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) is the percentage of patients who achieve a CR or PR
- Toxicity Profile [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]Toxicity is assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Toxicity profile is reported as the number of patients who received at least one dose of on-study treatment and experienced a grade 3 or grade 4 adverse event (AE). For a more complete listing of all AEs experienced by patients on study, please see the Adverse Event section.
|Study Start Date:||April 2010|
|Study Completion Date:||February 2015|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm 1: VELCADE and Sorafenib
Patients will be given VELCADE® (bortezomib) 1mg/m2 intravenously on days 1,4,8 & 11 and sorafenib at a dosage of 200 mg orally twice per day. One full course is comprised of 21 days.
Drug: Velcade and Sorafenib
Velcade will be administered intravenously; sorafenib will be self-administered on an outpatient basis. At least 2 courses will be administered to each patient unless there is early progression of disease or unacceptable toxicity. Repeated courses may be given to patients who benefit from the treatment (complete or partial remission or stabilization of disease)
- Pretreatment, a complete history and physical examination to include performance status, weight and concurrent non-malignant disease and therapy will be done before starting treatment. Prior surgery, chemotherapy, and radiotherapy details will be noted.
- Prior to the initiation of treatment, laboratory studies should include a CBC with differential cell count, platelet count, urinalysis, complete metabolic profile, magnesium and electrocardiogram. A baseline imaging study of the tumor will be performed. Other X-rays will be done as clinically indicated.
- Physical examination, performance status and toxicity recording will be done before each course of therapy.
- During the study, patients will be followed with complete blood count (CBC), differential and platelet counts on days 1, 4, 8, and 11. Chemistries will also be performed before each course within a 3 day leeway prior to treatment. Clinical schedules will be considered when scheduling patients for treatment, specimen collection and processing, and specimen shipment.
- Measureable and evaluable disease will be evaluated by the same imaging studies done at baseline and every 2 courses thereafter to determine tumor response.
- For patients on warfarin, International Normalized Ration (INR) testing will be performed prior to the first cycle, weekly during the first cycle, and then prior to day one for subsequent cycles if the INR is in an acceptable range during the first cycle. If the INR has not been in an acceptable range during the first cycle, the INR will be monitored weekly until the value is stable on three consecutive measurements one week apart.
- Since Sorafenib is a competitive inhibitor of cytochrome P450 isoenzyme 3A4 (CYP3A4) patients will be assessed each cycle for medications or changes in diet that would affect CYP3A4 metabolism.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01100242
|United States, New Mexico|
|University of New Mexico Cancer Center|
|Albuquerque, New Mexico, United States, 87106|
|The Cancer Center at Presbyterian|
|Albuquerque, New Mexico, United States, 87110|
|Memorial Medical Center- Cancer Center|
|Las Cruces, New Mexico, United States, 88011|
|Principal Investigator:||Richard Lauer, MD||New Mexico Cancer Care Alliance|