Clinical trial NCT00853021: Bevacizumab and Aldesleukin in Treating Patients With Metastatic Clear Cell Carcinoma of the Kidney
Official title: Phase II Open Label Trial of rIL-2 and Bevacizumab Combination in Patients With Metastatic Clear Cell Renal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Cancer
Keywords: clear cell renal cell carcinoma
recurrent renal cell cancer
stage IV renal cell cancer
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-02-27
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Biological therapies, such as aldesleukin, may stimulate the immune system in different ways and stop tumor cells from growing. Giving bevacizumab together with aldesleukin may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with aldesleukin works in treating patients with metastatic clear cell carcinoma of the kidney.

Detailed description: OBJECTIVES:

Primary

* To evaluate the effect of the combination of bevacizumab and aldesleukin on progression-free survival of patients with good- or intermediate-risk metastatic clear cell renal cell carcinoma.

Secondary

* To determine the objective response rate in patients receiving this regimen.
* To determine the time to progression in patients receiving this regimen.
* To evaluate immunomodulatory effects of this regimen in patients
* To evaluate the toxicity of this regimen in these patients.

OUTLINE: Patients receive bevacizumab IV over 30-90 minutes on days -14, 1, 15, 29, and 42 and aldesleukin subcutaneously on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Courses repeat every 8 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving complete response after completion of study therapy may receive 1 additional course of therapy.

After completion of study therapy, patients are followed periodically.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed renal cell carcinoma (RCC) of clear cell histology with or without sarcomatoid features

  * Metastatic disease
  * No non-clear cell RCC (i.e., papillary, collecting-duct, or chromophobe)
* Good- or intermediate-risk category as defined by having ≤ 2 of the following factors:

  * No prior nephrectomy
  * Karnofsky performance status \< 80%
  * Hemoglobin \< 12 g/dL
  * Corrected calcium \> 10.0 mg/dL
  * LDH \> 1.5 times upper limit of normal (ULN)
* Must have undergone a nephrectomy at least 28 days ago
* Measurable or evaluable disease by RECIST
* No significant effusions and/or ascites
* No prior or concurrent brain or CNS metastasis

PATIENT CHARACTERISTICS:

* ECOG performance status 0-1
* Life expectancy of ≥ 3 months
* WBC ≥ 3,000/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 9.5 g/dL
* Creatinine ≤ 2.0 mg/dL
* Total bilirubin ≤ 1.5 mg/dL
* AST ≤ 5.0 times ULN
* Alkaline phosphatase ≤ 2.5 times ULN (≤ 10 times ULN with bone metastasis)
* Calcium ≤ 12 mg/dL
* Urine protein:creatinine ratio ≤ 1.0
* INR ≤ 1.5 (unless receiving warfarin therapy)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No uncontrolled seizure disorder
* No known HIV positivity
* No local or systemic infections requiring IV antibiotics within the past 28 days
* No significant traumatic injury in the past 28 days
* No serious non-healing wound, ulcer, or acute bone fracture
* No evidence of bleeding diathesis or coagulopathy
* No other malignancy except basal cell or squamous cell carcinoma of the skin, carcinoma in-situ of the uterine cervix, or any malignancy treated with curative intent and in complete remission for \> 3 years
* No history of serious systemic or severe cardiovascular disease, including any of the following:

  * Arterial thromboembolic event (including transient ischemic attack)
  * Cerebrovascular accident
  * Unstable angina
  * Myocardial infarction within the past 6 months
  * Uncontrolled hypertension (BP \> 160/110 mm Hg on medication)
  * Uncontrolled cardiac arrhythmia
  * Congestive heart failure
  * Angina pectoris
  * NYHA class III-IV cardiovascular disease
  * Peripheral vascular disease ≥ grade II
* No history of abdominal fistula and/or bowel or gastric perforation within the past 6 months
* No history of other diseases, metabolic dysfunction, or physical or laboratory examination findings giving reasonable suspicion of a disease or condition that contraindicate the use of investigational drugs, or that might affect the interpretation of study results, or that render patient at high-risk for treatment complications

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior organ allografts
* No prior systemic therapy for metastatic clear cell renal cell carcinoma
* At least 4 weeks since prior radiotherapy and recovered

  * Radiotherapy for control of pain from skeletal lesions allowed within the past 28 days
* More than 12 months since prior adjuvant therapy
* More than 7 days since prior fine-needle aspirations or core biopsies
* More than 28 days since prior and no concurrent major surgery requiring general anesthesia or open biopsy
* No concurrent aspirin, corticosteroids (except at replacement doses), barbiturates, or other investigational agents

Primary outcomes:
measure: Progression Free Survival
timeFrame: From baseline (day -14) to disease progression (reported at 2 years)
Secondary outcomes:
measure: Objective Response Rate (Complete and Partial Response)
timeFrame: 4 weeks after end of treatment
measure: Percentage of Patients With Constitutional Adverse Events
timeFrame: From start of treatment to 30 days after treatment
measure: Percentage of Patients With Neutropenia
timeFrame: From start of treatment to 30 days after treatment
Other outcomes:
measure: Peripheral Blood CD1c+ Myeloid Dendritic Cells
timeFrame: Baseline (day -14), Beginning and end of cycle 1 (day 1, 57)
measure: CD303+ Plasmacytoid Dendritic Cells
timeFrame: Baseline (day -14), beginning and end of cycle 1 (day 1, 57)
measure: IL-8 Levels
timeFrame: Baseline (day -14), beginning and end of cycle 1 (day 1, 57)
measure: CD4+ Treg Cells
timeFrame: Baseline (day -14), beginning and end of cycle 1 (day 1, 57)
measure: CD25+ Treg Cells
timeFrame: Baseline (day -14), beginning and end of cycle 1 (day 1, 57)
measure: T-helper Cells (Type 1,2)
timeFrame: Baseline (day -14), beginning and end of cycle 1 (day 1, 57)
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: Jorge A. Garcia, MD
role: PRINCIPAL_INVESTIGATOR
References: