Doxorubicin and Gemcitabine in Treating Patients With Locally Recurrent or Metastatic Unresectable Renal Cell Carcinoma

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as doxorubicin and gemcitabine, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving doxorubicin together with gemcitabine works in treating patients with locally recurrent or metastatic unresectable renal cell carcinoma (kidney cancer).

Detailed Description
-----------------
OBJECTIVES: Determine the response rate of patients with locally recurrent or metastatic unresectable renal cell cancer with sarcomatoid features treated with doxorubicin and gemcitabine. Determine the progression-free survival and overall survival of patients treated with this regimen. Determine the toxic effects of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive doxorubicin intravenously (IV) and gemcitabine IV over 30 minutes on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 2- or 3-10 or pegfilgrastim SC on day 2. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. After 6 courses, patients undergo a MUGA scan. Patients with a stable* left ventricular ejection fraction (LVEF) continue therapy as above. Patients who reach a total doxorubicin dose of 450 mg/m^2 and are found to have unstable cardiac function or who have an abnormal LVEF continue therapy with gemcitabine alone. NOTE: *Stable cardiac function is defined as no decrease more than 15% of LVEF in absolute number and LVEF at least 35% in total function by MUGA. Patients are followed every 3 months for 2 years and then every 6 months for 1 year. ACTUAL ACCRUAL: A total of 39 patients were accrued for this study.

Official Title
-----------------
Phase II Trial of Doxorubicin and Gemcitabine in Metastatic Renal Cell Carcinoma With Sarcomatoid Features

Conditions
-----------------
Metastatic Renal Cell Carcinoma, Renal Cell Carcinoma With Sarcomatoid Features

Intervention / Treatment
-----------------
* Drug: Doxorubicin
* Drug: Gemcitabine
* Drug: G-CSF (granulocyte-colony stimulating factor)
* Drug: Neulasta


Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA: Histologically confirmed renal cell carcinoma Features must be of sarcomatoid histology Locally recurrent or metastatic disease not amenable to resection Measurable disease Must have a prior nephrectomy provided all other eligibility criteria are met, and adequately recovered from any recent surgery At least 4 weeks since prior radiotherapy and recovered ECOG performance status of 0-1 WBC greater than 3,000/mm^3 or absolute neutrophil count greater than 1,500/mm^3 Platelet count greater than 100,000/mm^3 Bilirubin less than 1.5 mg/dL Aspartate aminotransferase (AST) less than 2 times upper limit of normal Creatinine no greater than 2.0 mg/dL LVEF at least lower limit of normal by MUGA Negative pregnancy test Fertile patients must use effective contraception Other prior malignancy allowed provided patient was curatively treated and has been disease free from that cancer Age of 18 and over Diagnostic material from the kidney or metastatic site biopsy available for central pathologic review EXCLUSION CRITERIA: Prior treatment for advanced disease Previously irradiated lesions as the sole site of disease for patients with prior radiation therapy Concurrent local radiotherapy for pain control or for life-threatening situations Myocardial infarction within the past year Congestive heart failure within the past year Significant ischemic or valvular heart disease within the past year Prior or concurrent brain metastases Concurrent serious medical illness that would preclude study treatment Active infection that would preclude study treatment Pregnant or nursing

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Doxorubicin/Gemcitabine<br>Doxorubicin was given at 50 mg/m² by IV slow push, followed by gemcitabine 1500 mg/m² IV infusion over 30 minutes on day 1. Patients will receive G-CSF at a subcutaneous dose of 5mcg/kg/day on days 2 or 3 to 10 or neulasta at a dose of 6mg on day 2. Growth factor must be administered as close as possible to 24 hours after the completion of chemotherapy. It is recommended that neulasta be administered only on day 2 due to its prolonged half-life. Cycles were repeated every 2 weeks. | Drug: Doxorubicin<br>* Doxorubicin: 50 mg/m² IV slow push followed by gemcitabine 1500 mg/m² IV infusion over 30 minutes on day 1. Cycles repeat every 2 weeks.<br>* Other names: Rubex;Drug: Gemcitabine<br>* Doxorubicin: 50 mg/m² IV slow push followed by gemcitabine 1500 mg/m² IV infusion over 30 minutes on day 1. Cycles repeat every 2 weeks.<br>Drug: G-CSF (granulocyte-colony stimulating factor)<br>* Patients will receive G-CSF at a subcutaneous dose of 5mcg/kg/day on days 2 or 3 to 10 or neulasta at a dose of 6mg on day 2. Growth factor must be administered as close as possible to 24 hours after the completion of chemotherapy. It is recommended that neulasta be administered only on day 2 due to its prolonged half-life.<br>* Other names: Filgrastim;Drug: Neulasta<br>* Patients will receive G-CSF at a subcutaneous dose of 5mcg/kg/day on days 2 or 3 to 10 or neulasta at a dose of 6mg on day 2. Growth factor must be administered as close as possible to 24 hours after the completion of chemotherapy. It is recommended that neulasta be administered only on day 2 due to its prolonged half-life.<br>* Other names: pegfilgrastim;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate by Solid Tumor Response Criteria (RECIST) | Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR | Every 8 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-3 years from study entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival is defined as the time from study entry until death from any cause. | Every 2 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-3 years from study entry | 
| Progression-free Survival | Progression-free survival is defined as time from study entry until disease progression or death from any cause, whichever occurs first. Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions. | Every 8 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-3 years from study entry | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gemcitabine, Sarcomatoid, Doxorubicin, Renal cell cancer, Kidney cancer