Clinical trial NCT00496587: Capecitabine, Gemcitabine, and Bevacizumab in Combination for Patients With Sarcomatoid Renal Cell Carcinoma
Official title: Phase II Safety and Efficacy Study of Capecitabine, Gemcitabine, and Bevacizumab in Combination for Patients With Metastatic or Unresectable Sarcomatoid Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Cell Carcinoma
Kidney Cancer
Keywords: Genitourinary
Kidney Cancer
Sarcomatoid Renal Cell Carcinoma
Renal Cell Carcinoma
RCC
Sarcomatoid Carcinoma of the Kidney
Unresectable renal cell carcinoma
Capecitabine
Xeloda
Gemcitabine
Gemzar
Bevacizumab
Anti-VEGF monoclonal antibody
rhuMAb-VEGF
Avastin
Vascular Endothelial Growth Factor
VEGF
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2007-07-04
Enrollment: 34
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical research study is to learn if the combination of 3 drugs (gemcitabine, capecitabine, and bevacizumab) can help to control metastatic or unresectable renal cell carcinoma. The safety of this drug combination will also be tested.

Detailed description: Gemcitabine and capecitabine are designed to disrupt the growth of cancer cells, which may cause cancer cells to start to die. Bevacizumab is a drug that binds to and inhibits Vascular Endothelial Growth Factor (VEGF), a blood-vessel stimulating agent with unusually high levels in kidney cancer.

If you are found to be eligible to take part in this study, you will receive gemcitabine, capecitabine, and bevacizumab on a 28 day cycle. Capecitabine will be taken by mouth (with food), twice daily, on Days 1-21. Gemcitabine will be given through a needle in your vein in your arm over 30 minutes on Days 1 and 15. Bevacizumab will be given through a needle in your vein in your arm on Days 1 and 15. It will be given over 120 minutes for Cycle 1 and over 60 minutes for all other cycles. Your doctor may decided to give you bevacizumab over 30 minutes if you tolerate the treatment well.

On the first day of each cycle, blood (about 2 teaspoons) and a urine will be collected before treatment for routine tests. You will also have blood drawn on Day 15 (about 2 teaspoons) for routine tests.

Every 8 weeks, you will have a CT scan of your chest, abdomen, and pelvis and a chest x-ray. You will be asked about any drugs that you are currently taking and you will have a complete physical exam. You will be asked about any side effects that you might have experienced since the last visit and your ability to perform daily activities will be evaluated. Repeat bone scans and MRI of the brain may be done if your doctor thinks it is necessary.

You will continue receiving treatment for a maximum of 12 months. However, if you are benefitting from treatment, you may be able to continue receiving it off study. You will be taken off study if the disease gets worse, if the side effects are intolerable, or if you develop another illness that prevents you from receiving the treatment.

This is an investigational study. Gemcitabine, capecitabine, and bevacizumab are all FDA approved and commercially available. Up to 40 participants may take part in this study. All will be enrolled at MD Anderson.

Eligibility criteria: Inclusion Criteria:

1. Histologically demonstrated, metastatic or unresectable sarcomatoid carcinoma of the kidney, defined as the following: • A tumor biopsy (primary or metastasis) must show at least one focus of RCC (one of the recognized types); and, • A tumor biopsy (primary or metastasis) must have at least 10% of the sample showing sarcomatoid histology.
2. (# 1 cont'd) • Patients with primary tumor in place are eligible if there is any percentage of sarcomatoid dedifferentiation on a needle biopsy (primary or metastasis), and the radiographic appearance of the primary tumor on CT scan is typical of RCC. For these patients, due to the small tumor sample, it is not required to identify an area of typical RCC histology as long as the morphologic and immunostaining characteristics are consistent with RCC.
3. At least one site of measurable disease (may include primary tumor).
4. No prior cytotoxic chemotherapy. Any prior immunotherapy is permitted.
5. No prior bevacizumab treatment. Prior sorafenib or sunitinib is permitted.
6. Zubrod performance status 2 or better
7. Adequate organ and bone marrow function: • Absolute Neutrophil Count (ANC) \>/= 1,500 • Platelets \>/=100,000 • Total bilirubin \</= 1.5 mg/dl • AST and ALT \</= 3x upper limit normal • Creatinine clearance \> 50 cc/min (measured or calculated by Cockcroft formula: Creatinine Clearance = \[(140 - age) x wt (kg)\]/\[72 x creat (mg/dl)\], for females x 0.85. Patients with creatinine clearance of 30-50 ml/min are eligible with an initial dose-reduction of capecitabine to the (-1) dose level.
8. Female patients of childbearing potential (last menses \< 2 years) must have a negative blood pregnancy test within 7 days prior to starting treatment.
9. All patients must agree to practice adequate contraception if sexually active for the duration of the trial and for 2 months after discontinuation of the study drugs
10. Written informed consent.

Exclusion Criteria:

1. Patients with history of myocardial infarction, transient ischemic attack (TIA), stroke, pulmonary embolism, or history of deep vein thrombosis within the preceding 12 months.
2. Patients with major risk of bleeding, such as active brain metastases. Patients with controlled or small brain metastases will be eligible based on clinical assessment of the actual bleeding risk.
3. Patients with history of any major surgical procedure within the preceding 28 days.
4. Patients with baseline blood pressure \>/= 140 systolic or \>/= 90 diastolic.
5. Patients with nephrotic syndrome (proteinuria \> 2 grams per 24 hours)
6. History of other malignancy, unless it is clinically non-threatening (such as non-melanoma skin cancer) or controlled for 2 years prior to study entry.
7. Prior treatment with gemcitabine, capecitabine, or any fluoropyrimidine.
8. Prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-FU.
9. Any concurrent chemotherapy or radiotherapy.
10. Lack of physical integrity of the upper gastrointestinal tract, inability to swallow tablets or those who have malabsorption syndrome.
11. Clinically significant cardiac disease not well controlled with medication, such as symptomatic coronary artery disease, congestive heart failure, and cardiac arrhythmias.
12. Serious concurrent infections or other serious medical conditions, including uncontrolled diabetes.
13. Any serious non-healing wound, ulcer, or active bone fracture.
14. Any concurrent coumadin therapy. Patients who were previously on coumadin maintenance may switch to aspirin or low-molecular-weight heparin.
15. Patients who have had an organ allograft.
16. Unwillingness to give written informed consent.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 12 months or until progression of disease
measure: Time to Treatment Failure (TTF)
timeFrame: 12 months or until progression of disease
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 12 months or until progression of disease
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Nizar M. Tannir, MD
role: PRINCIPAL_INVESTIGATOR
References: