Metastatic Renal Cell Carcinoma
Conditions
Keywords
Renal Cell Carcinoma, metastatic renal cell cancer, kidney cancer
Brief summary
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
Detailed description
* 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.
Interventions
DRUGVelcade 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)
Sponsors
New Mexico Cancer Research Alliance
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
Each patient must meet all of the following inclusion criteria to be enrolled in the study: * Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. * Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. * Male subject agrees to use an acceptable method for contraception for the duration of the study. * All patients, 18 years or older with cytologically confirmed clear cell renal with no prior chemotherapy are eligible. * Patients must have a life expectancy of at least 12 weeks * Patients must have a Zebroid performance of 0-2 * Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of \> 1500 cells/mm3 and platelet count \> 100,000/mm3 and absence of a regular red blood cell transfusion requirement. * Patients should have adequate hepatic function with a total bilirubin \< 2 mg/dl and Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) \< two times the upper limit of normal, and adequate renal function as defined by a Serum creatinine \< 1.5 x the upper limit of normal.
Exclusion criteria
Patients meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 36 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 42 days | 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 | 42 days | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VELCADE and Sorafenib VELCADE® (bortezomib) 1mg/m2 intravenously on days 1,4,8 & 11 and sorafenib at 200 mg orally twice per day. One full course is comprised of 21 days. | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | VELCADE and Sorafenib |
|---|---|
| Age, Continuous | 61 years |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 17 |
| serious Total, serious adverse events | 6 / 17 |
Outcome results
Primary
Progression Free Survival (PFS)
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.
Time frame: 36 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VELCADE and Sorafenib | Progression Free Survival (PFS) | 13.71 weeks |
Secondary
Overall Response Rate (ORR)
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
Time frame: 42 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VELCADE and Sorafenib | Overall Response Rate (ORR) | Complete response (CR) | 0 percentage of participants |
| VELCADE and Sorafenib | Overall Response Rate (ORR) | Partial response (PR) | 5.9 percentage of participants |
| VELCADE and Sorafenib | Overall Response Rate (ORR) | Overall response rate (CR + PR) | 5.9 percentage of participants |
Secondary
Toxicity Profile
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.
Time frame: 42 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VELCADE and Sorafenib | Toxicity Profile | Abdominal pain | 2 participants |
| VELCADE and Sorafenib | Toxicity Profile | Hyponatremia | 5 participants |
| VELCADE and Sorafenib | Toxicity Profile | Hypophosphatemia | 4 participants |
| VELCADE and Sorafenib | Toxicity Profile | Lymphopenia | 4 participants |
| VELCADE and Sorafenib | Toxicity Profile | Decreased platelets | 1 participants |
| VELCADE and Sorafenib | Toxicity Profile | Weight loss | 2 participants |
| VELCADE and Sorafenib | Toxicity Profile | Anorexia (loss of appetite) | 2 participants |
| VELCADE and Sorafenib | Toxicity Profile | Dehydration | 1 participants |
| VELCADE and Sorafenib | Toxicity Profile | Fatigue | 2 participants |
| VELCADE and Sorafenib | Toxicity Profile | Hand and foot syndrome | 1 participants |
| VELCADE and Sorafenib | Toxicity Profile | Hemoglobin | 2 participants |
| VELCADE and Sorafenib | Toxicity Profile | Hyperglycemia | 1 participants |
| VELCADE and Sorafenib | Toxicity Profile | Hypertension | 1 participants |
| VELCADE and Sorafenib | Toxicity Profile | Hypoalbuminemia | 3 participants |
| VELCADE and Sorafenib | Toxicity Profile | Hypokalemia | 1 participants |
| VELCADE and Sorafenib | Toxicity Profile | Pain - Other (All over body) | 1 participants |
| VELCADE and Sorafenib | Toxicity Profile | Pain in extremity | 1 participants |