Clear Cell Renal Cell Carcinoma, Recurrent Renal Cell Cancer, Stage IV Renal Cell Cancer
Conditions
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.
Interventions
DRUGcediranib maleate
Given orally
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response | Up to 6 weeks | Objective radiologic response as measured by RECIST criteria. (30% or greater shrinkage in the sum of the longest diameters of target lesions) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Performance of DCE_MRI | One month after initiating therapy | Binary (yes/no) indicator of whether a dynamic contrast-enhanced MRI (DCE-MRI)was successfully performed. |
| KDR | Day 28 after initiation of therapy | Kinase insert domain-containing vascular endothelial growth factor receptor |
| eNOS | Baseline (prior to therapy) | Endothelial nitric oxide synthase gene (eNOS). Record genotype=number of minor alleles. |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled between December, 2006 and July, 2007 at three institutions. The trial was terminated after 10 patients were enrolled due to insufficent accrual rate.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Cediranib Maleate) Patients receive oral AZD2171 once daily for 4 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Treatment (Cediranib Maleate) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 63.8 years STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Objective Response
Objective radiologic response as measured by RECIST criteria. (30% or greater shrinkage in the sum of the longest diameters of target lesions)
Time frame: Up to 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Cediranib Maleate) | Objective Response | 20 percentage of participants |
Secondary
eNOS
Endothelial nitric oxide synthase gene (eNOS). Record genotype=number of minor alleles.
Time frame: Baseline (prior to therapy)
Population: Because trial was closed due to poor accrual, assays were not performed.
Secondary
KDR
Kinase insert domain-containing vascular endothelial growth factor receptor
Time frame: Day 28 after initiation of therapy
Population: Because trial was closed due to poor accrual, assays were not performed.
Secondary
Performance of DCE_MRI
Binary (yes/no) indicator of whether a dynamic contrast-enhanced MRI (DCE-MRI)was successfully performed.
Time frame: One month after initiating therapy
Population: Because trial was closed due to poor accrual, MRI data were not collected.