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

Eastern Cooperative Oncology Group

Status and phase: Completed; Phase 2

Conditions: Renal Cell Carcinoma With Sarcomatoid Features; Metastatic Renal Cell Carcinoma

Treatments: Drug: Gemcitabine; Drug: Neulasta; Drug: G-CSF (granulocyte-colony stimulating factor); Drug: Doxorubicin

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00068393

CDR0000322258

E8802 (Other Identifier)

U10CA021115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 39 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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39 participants in 1 patient group

Doxorubicin/Gemcitabine

Experimental group

Description:

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.

Treatment:

Drug: Doxorubicin

Drug: Neulasta

Drug: G-CSF (granulocyte-colony stimulating factor)

Drug: Gemcitabine