A Dose Escalation Phase II Study of Sunitinib Plus Erlotinib in Advanced Renal Carcinoma
A Dose Escalation Phase II Study of Sunitinib Plus Erlotinib in Advanced Renal Carcinoma
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.
OBJECTIVES:
Primary
Secondary
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.
DISEASE CHARACTERISTICS:
Histologically confirmed renal cell carcinoma with a component of clear cell or papillary carcinoma
Measurable disease (≥ 1 site)
No known brain metastasis that has not been adequately treated with radiotherapy and/or surgery
PATIENT CHARACTERISTICS:
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
No grade 3 hemorrhage within the past 4 weeks
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times ULN (< 5 times ULN if due to underlying disease)
No chronic liver disease (i.e., chronic active hepatitis or cirrhosis)
Creatinine ≤ 1.5 times ULN
None of the following cardiovascular conditions within the past 12 months:
Left Ventricular Ejection Fraction (LVEF) normal by Multigated Acquisition (MUGA) or echocardiogram
No hypertension uncontrolled with medical therapy
No other active malignancy within the past 5 years except basal cell skin cancer or cervical carcinoma in situ
No uncontrolled adrenal insufficiency
No uncontrolled hypothyroidism
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
No severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection)
No impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs
No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
More than 4 weeks since prior major surgery
More than 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin C)
More than 4 weeks since prior radiotherapy
No prior radiotherapy to > 25% of the bone marrow
More than 28 days since prior investigational agents
No prior sunitinib malate
No prior anti-epidermal growth factor receptor therapy (e.g., erlotinib hydrochloride, panitumumab, cetuximab, or gefitinib)
No concurrent therapeutic warfarin
No concurrent Hypericum perforatum (St. John's wort)
No concurrent chemotherapy or biologic therapy
No other concurrent anticancer therapy
No other concurrent investigational agents