Clinical trial NCT00326898
Conditions: Clear Cell Renal Cell Carcinoma Stage I Renal Cell Cancer AJCC v6 and v7 Stage II Renal Cell Cancer AJCC v7 Stage III Renal Cell Cancer AJCC v7
Sponsor: National Cancer Institute (NCI)
Start date: 2006-04-24; Completion date: 2021-09-01
Enrollment: 1943 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This randomized phase III trial studies sunitinib malate to see how well it works compared to sorafenib tosylate or placebo in treating patients with kidney cancer that has been removed by surgery. Sunitinib malate and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib malate or sorafenib tosylate after surgery may kill any tumor cells that remain after surgery. It is not yet known whether sunitinib malate is more effective than sorafenib tosylate or placebo in treating kidney cancer.

Detailed description:
PRIMARY OBJECTIVES:

I. To demonstrate an improvement in disease-free survival in locally advanced renal cell carcinoma patients randomly assigned to adjuvant sunitinib (sunitinib malate) (Arm A) or sorafenib (sorafenib tosylate) (Arm B) versus placebo (Arm C) after radical or partial nephrectomy.

SECONDARY OBJECTIVES:

I. To compare overall survival of patients randomized to each of the two regimens with placebo.

II. To further define the toxicity of prolonged administration of sunitinib or sorafenib in this patient population.

III. To prospectively collect tumor and biological specimens to assess their characteristics and associations: novel approaches to assess angiogenesis markers in tissue, blood and urine as predictors of disease-free survival and of therapeutic benefit.

IV. To prospectively collect tumor and biological specimens to assess their characteristics and associations: the frequency of oncogene and tumor suppressor gene mutations as predictors of disease-free survival and therapeutic benefit.

V. To prospectively collect tumor and biological specimens to assess their characteristics and associations: tumor and genetic polymorphisms as predictors of disease-free survival and therapeutic benefit.

VI. To prospectively collect tumor and biological specimens to assess their characteristics and associations: deoxyribonucleic acid (DNA) methylation profiles as predictors of outcome and of therapeutic benefit.

VII. To prospectively collect tumor and biological specimens to assess their characteristics and associations: The relationship of polymorphisms in drug metabolizing enzymes with steady state concentrations of sorafenib and sunitinib in selected patients.

VIII. To study the effect of vascular endothelial growth factor (VEGF) targeted therapy on circulating endothelial cells and circulating endothelial progenitors.

IX. To prospectively assess patient-reported fatigue in order to compare the magnitude and trajectory of fatigue among renal cell carcinoma (RCC) patients randomized to adjuvant sunitinib (Arm A) or sorafenib (Arm B) to placebo (Arm C). (Quality of life objectives) X. To evaluate the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short Form (SF)1, a newly developed state-of-the-science PROMIS measure for fatigue and to calibrate the PROMIS Fatigue-SF1 with the established, validated FACIT-Fatigue scale. (Quality of life objectives)

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM A: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sunitinib malate orally (PO) once daily (QD) for 4 weeks and placebo sorafenib tosylate PO QD or twice daily (BID) for 6 weeks.

ARM B: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sorafenib tosylate PO QD or BID for 6 weeks and placebo sunitinib malate PO QD for 4 weeks followed.

ARM C: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive placebo sorafenib tosylate as in Arm A and placebo sunitinib malate as in Arm B.

In all arms, treatment repeats every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 5 years.

Arms: arm 1: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sunitinib malate PO QD for 4 weeks and placebo sorafenib tosylate PO QD or BID for 6 weeks. arm 2: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sorafenib tosylate PO QD or BID for 6 weeks and placebo sunitinib malate PO QD for 4 weeks followed. arm 3: Beginning 4-12 weeks following radical or partial nephrectomy, patients receive placebo sorafenib tosylate as in Arm A and placebo sunitinib malate as in Arm B.
Interventions: intervention 1: Laboratory Biomarker Analysis intervention 2: Placebo intervention 3: Quality-of-Life Assessment intervention 4: Sorafenib Tosylate intervention 5: Sunitinib Malate
Intervention descriptions: intervention 1: Correlative studies intervention 2: Given PO intervention 3: Ancillary studies intervention 4: Given PO intervention 5: Given PO

Protocol documents: