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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00068393
First received: September 10, 2003
Last updated: January 4, 2013
Last verified: January 2013
  Purpose

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).


Condition Intervention Phase
Metastatic Renal Cell Carcinoma
Renal Cell Carcinoma With Sarcomatoid Features
Drug: Doxorubicin
Drug: Gemcitabine
Drug: G-CSF (granulocyte-colony stimulating factor)
Drug: Neulasta
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Doxorubicin and Gemcitabine in Metastatic Renal Cell Carcinoma With Sarcomatoid Features

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Response Rate by Solid Tumor Response Criteria (RECIST) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from study entry until death from any cause.

  • Progression-free Survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 39
Study Start Date: December 2003
Study Completion Date: May 2011
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doxorubicin/Gemcitabine
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
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.
Other Names:
  • Adriamycin
  • Rubex
Drug: 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.
Drug: 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.
Other Names:
  • Neupogen
  • Filgrastim
Drug: 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.
Other Name: pegfilgrastim

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00068393

  Show 92 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Naomi S. Balzer-Haas, MD Fox Chase Cancer Center
  More Information

Additional Information:
Publications:
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.

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00068393     History of Changes
Other Study ID Numbers: CDR0000322258, E8802, U10CA021115
Study First Received: September 10, 2003
Results First Received: November 30, 2012
Last Updated: January 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Eastern Cooperative Oncology Group:
Sarcomatoid
Gemcitabine
Doxorubicin
Renal cell cancer
Kidney cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Doxorubicin
Gemcitabine
Lenograstim
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on July 29, 2014