Sunitinib and Erlotinib in Treating Patients With Unresectable or Metastatic Kidney Cancer
RATIONALE: Sunitinib and erlotinib may stop the growth of tumor cell by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib together with erlotinib may kill more tumor cells.
PURPOSE: This phase II trial is studying the best dose of erlotinib when given together with sunitinib and to see how well they work in treating patients with unresectable or metastatic kidney cancer.
Drug: erlotinib hydrochloride
Drug: sunitinib malate
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Dose Escalation Phase II Study of Sunitinib Plus Erlotinib in Advanced Renal Carcinoma|
- Maximum Tolerated Dose (MTD) of Erlotinib Hydrochloride When Used in Combination With Sunitinib. [ Time Frame: Participants assessed for DLTs weekly during the first cycle of treatment and every 3 weeks in subsequent cycles until at least one DLT occurs in 33% or more of participants at that dose; participants assessed for the duration of the study, up to 7 years ] [ Designated as safety issue: Yes ]The MTD is defined as the dose that produces dose limiting toxicity (DLT) in 33% of the patients.
- Progression-free Survival at 8 Months [ Time Frame: 8 months after initiating treatment with sunitinib in combination with erlotinib in patients with metastatic or unresectable clear cell or papillary carcinoma of the kidney ] [ Designated as safety issue: No ]Defined as the proportion of patients who are progression free (CR, PR and SD) at 8 months after initiating treatment with sunitinib in combination with erlotinib in patients with metastatic or unresectable clear cell or papillary carcinoma of the kidney. Complete Response (CR)= disappearance of all target lesions, Partial Response (PR)= At least a 30% decrease in the sum of the longest diameter of target lesions, and Stable Disease (SD)= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (20% increase in the sum).
- To Determine the Safety of Sunitinib in Combination With Erlotinib [ Time Frame: For the duration of the study, up to 7 years ] [ Designated as safety issue: Yes ]
- Median Time to Progression [ Time Frame: For the duration of the study, up to 7 years ] [ Designated as safety issue: No ]The Kaplan-Meier method will be used to estimate the median time to progression.
- Proportion of Patients Whose Best Overall Response is Complete Response, Partial Response, Stable Disease, or Progressive Disease [ Time Frame: From the start of treatment until the criteria for response is met. ] [ Designated as safety issue: No ]
- Maximum Percent Change in Tumor Measurement [ Time Frame: Baseline through end of study, up to 7 years ] [ Designated as safety issue: No ]The maximum percent change in Tumor Measurement is the greatest percent change in longest diameter (LD) for the target lesions from the baseline LD. For patients with no change in LD, the maximum percent change is the lowest increase in LD from the baseline LD.
|Study Start Date:||August 2006|
|Study Completion Date:||March 2014|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
Experimental: Erlotinib and Sunitinib
Drug: erlotinib hydrochloride Dose Level 0 = 50 mg/day, continuous daily; 0.5= 75 mg/day, continuous daily;
Drug: sunitinib malate Will be administered at 50 mg daily, 4 weeks on, 2 weeks off
Drug: erlotinib hydrochloride
Drug: sunitinib malate
Dose Level 0 = 50 mg/day, continuous daily; 0.5= 75 mg/day, continuous daily;
Will be administered at 50 mg daily, 4 weeks on, 2 weeks offProcedure: biopsy
Paraffin block (or unstained slides) of the primary tumor and/or metastatic lesions (as available) and a plasma sample for future correlative studies will be collected. A paraffin block (or at least 10 unstained slides, each of 10 micromillimeter thickness) from the original paraffin-embedded biopsy material taken at the diagnosis will be stored at 4 degrees Celsius.
- Determine the maximum tolerated dose of erlotinib hydrochloride when administered with sunitinib malate in patients with unresectable or metastatic renal cell carcinoma.
- Determine the 8-month progression-free survival of patients treated with this regimen.
- Determine the safety of sunitinib malate and erlotinib hydrochloride in these patients.
- Determine the duration of response in these patients.
- Determine the proportion of patients whose best overall response is complete response, partial response, stable disease, or progressive disease.
- Determine the overall survival of patients treated with this regimen.
- Determine the maximum percent reduction in tumor measurement in patients treated with this regimen.
- Collect blood and tissue from these patients for future correlative studies.
OUTLINE: This is an open-label, multicenter, dose-escalation study of erlotinib hydrochloride.
Patients receive oral sunitinib malate once daily on days 1-28 and oral erlotinib hydrochloride once daily on days 1-42. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 33% of patients experience dose-limiting toxicity. Once the MTD is determined, patients are treated with erlotinib hydrochloride at the MTD and sunitinib malate.
Patients undergo blood and tumor specimen collection periodically during study for future correlative studies.
PROJECTED ACCRUAL: A total of 49 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00425386
|United States, California|
|University of Southern California|
|Los Angeles, California, United States, 90033|
|United States, Oregon|
|Providence Cancer Center at Providence Portland Medical Center|
|Portland, Oregon, United States, 97213-2967|
|OHSU Knight Cancer Institute|
|Portland, Oregon, United States, 97239-3098|
|Salem, Oregon, United States, 97301|
|Study Chair:||Christopher W. Ryan, MD||OHSU Knight Cancer Institute|