Clinical trial NCT00303862: AZD2171 in Treating Patients With Refractory Metastatic Kidney Cancer
Official title: A Phase 2 Study of AZD2171 in Patients With Advanced Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Clear Cell Renal Cell Carcinoma
Recurrent Renal Cell Cancer
Stage IV Renal Cell Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-03-17
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed clear cell renal cell cancer

  * Must be predominantly metastatic disease
  * Refractory disease
* 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

Primary outcomes:
measure: Objective Response
timeFrame: Up to 6 weeks
Secondary outcomes:
measure: Performance of DCE_MRI
timeFrame: One month after initiating therapy
measure: KDR
timeFrame: Day 28 after initiation of therapy
measure: eNOS
timeFrame: Baseline (prior to therapy)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
Study officials:
affiliation: University of Chicago
name: Walter Stadler
role: PRINCIPAL_INVESTIGATOR
References: