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

Metastatic Renal Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00068393
• Other study ID #: CDR0000322258
• Secondary ID: E8802U10CA021115
• Status: Completed
• Phase: Phase 2
• Start date: February 24, 2004
• Est. completion date: May 2011

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: May 2011
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma
• Renal Cell Carcinoma With Sarcomatoid Features

Intervention

Drug:
• Doxorubicin
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.
• Gemcitabine
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.
• G-CSF (granulocyte-colony stimulating factor)
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.
• Neulasta
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.

Locations

Country	Name	City	State
United States	McFarland Clinic, PC	Ames	Iowa
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado
United States	Billings Clinic Cancer Center	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Deaconess Billings Clinic - Downtown	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare	Billings	Montana
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Cancer Research Center at Boston Medical Center	Boston	Massachusetts
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Our Lady of Mercy Medical Center Comprehensive Cancer Center	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	St. James Community Hospital	Butte	Montana
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Mercy Hospital and Medical Center	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	CCOP - Duluth	Duluth	Minnesota
United States	Miller-Dwan Medical Center	Duluth	Minnesota
United States	St. Mary's - Duluth Clinic Cancer Center	Duluth	Minnesota
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Hunterdon Regional Cancer Center at Hunterdon Medical Center	Flemington	New Jersey
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Great Falls Clinic	Great Falls	Montana
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	St. Peter's Hospital	Helena	Montana
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	William N. Wishard Memorial Hospital	Indianapolis	Indiana
United States	Foote Hospital	Jackson	Michigan
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Midwest Center for Hematology/Oncology	Joliet	Illinois
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Howard Community Hospital at Howard Regional Health System	Kokomo	Indiana
United States	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Central Pennsylvania Hematology and Medical Oncology Associates, PC	Lemoyne	Pennsylvania
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois
United States	St. Rita's Medical Center	Lima	Ohio
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical Consultants, Limited	Milwaukee	Wisconsin
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois
United States	Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital	Parkersburg	West Virginia
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Seton Cancer Institute - Saginaw	Saginaw	Michigan
United States	Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph	Saint Joseph	Michigan
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sioux Valley Hospital and University of South Dakota Medical Center	Sioux Falls	South Dakota
United States	Hematology Oncology Associates - Skokie	Skokie	Illinois
United States	Hematology/Oncology of the North Shore at Gross Point Medical Center	Skokie	Illinois
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Saint Joseph Regional Medical Center	South Bend	Indiana
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	CCOP - Hematology-Oncology Associates of Central New York	Syracuse	New York
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	St. John Macomb Hospital	Warren	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Haas N, Manola J, Pins M, et al.: ECOG 8802: phase II trial of doxorubicin (Dox) and gemcitabine (Gem) in metastatic renal cell carcinoma (RCC) with sarcomatoid features. [Abstract] J Clin Oncol 27 (Suppl 15): A-5038, 2009.

Haas NB, Lin X, Manola J, Pins M, Liu G, McDermott D, Nanus D, Heath E, Wilding G, Dutcher J. A phase II trial of doxorubicin and gemcitabine in renal cell carcinoma with sarcomatoid features: ECOG 8802. Med Oncol. 2012 Jun;29(2):761-7. doi: 10.1007/s1203 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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