A Phase 2 Study of AZD2171 in Patients With Advanced Renal Cell Carcinoma
A Phase 2 Study of AZD2171 in Patients With Advanced Renal Cell Carcinoma
This phase II trial is studying how well AZD2171 works in treating patients with refractory metastatic kidney cancer. AZD2171 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.
PRIMARY OBJECTIVES:
I. Determine the objective response rate in patients with refractory metastatic renal cell carcinoma treated with AZD2171.
SECONDARY OBJECTIVES:
I. Determine the safety and tolerability of AZD2171 in these patients. II. Determine the feasibility of performing standardized delayed contrast-enhancement-MRI correlative studies across different institutions and platforms with data-sharing capability in patients with metastatic renal cell cancer.
III. Generate preliminary data regarding potential utility of pharmacogenomic and plasma/serum biomarkers of angiogenesis as predictive or prognostic markers for future investigations of AZD2171 and renal cell carcinoma.
OUTLINE: This is a multicenter study.
Patients receive oral AZD2171 once daily for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for 6 weeks.
Inclusion Criteria:
Histologically or cytologically confirmed clear cell renal cell cancer
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mmby conventional techniques or ≥ 10 mm by spiral CT scan
No known brain metastases
ECOG performance status 0-2
Karnofsky 60-100%
WBC ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 8.0 g/dL
AST and ALT ≤ 2.5 times upper limit of normal (ULN)
Bilirubin normal
Creatinine normal OR creatinine clearance > 60 mL/min
Blood pressure < 140/90 mm Hg on 2 separate occasions not more than 6 weeks prior to enrollment and not less than 24 hours apart (stable antihypertensive regimen allowed)
Mean QTc ≤ 470 msec (with Bazett's correction)
Less than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of familial long QT syndrome
No cardiac arrhythmia
No unstable angina pectoris
No symptomatic congestive heart failure
No New York Heart Association class III or IV disease
No ongoing or active infection
No hypertension
No other uncontrolled intercurrent illness
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171
No psychiatric illness or social situations that would limit compliance with study requirements
See Disease Characteristics
More than 4 weeks since prior radiotherapy and recovered
More than 4 weeks since prior major surgery and recovered
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
More than 30 days since other prior investigational agents
No prior therapy with vascular endothelial growth factor (VEGF) binding agents or VEGF receptor (VEGFR) tyrosine kinase inhibitors
No more than 1 prior nonVEGF-directed systemic therapy for this disease
No concurrent medication that may markedly affect renal function (e.g., vancomycin, amphotericin, ibuprofen, pentamidine)
No combination antiretroviral therapy for HIV-positive patients
No concurrent hematopoietic growth factors except epoetin alfa and bisphosphonates
No concurrent hormones or other chemotherapeutic agents except for steroids given for adrenal failure and hormones administered for nondisease-related conditions (e.g. insulin for diabetes)
No concurrent palliative or therapeutic radiation therapy
No concurrent drugs or biologics with proarrhythmic potential
No other concurrent investigational or commercial agents or therapies to treat the patient's malignancy