Phase 2 Trial of Sequential Bevacizumab Then Subcutaneous Interleukin-2 in Metastatic Renal Cancer
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 19
- Locations
- 1
- Primary Endpoint
- Number of Evaluable Participants With Complete Response (CR) and Partial Response (PR) at One Year
Study Overview
Brief Summary
This phase II trial is studying how well giving bevacizumab together with interleukin-2 works in treating patients with metastatic kidney cancer. 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. Interleukin-2 may stimulate the white blood cells to kill tumor cells. Giving bevacizumab together with interleukin-2 may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES:
I. Determine the frequency of major response in patients with metastatic renal cell cancer treated with bevacizumab and interleukin-2.
SECONDARY OBJECTIVES I. Compare the median progression-free survival and median overall survival of patients treated with this regimen with risk-stratified historical controls from published risk models.
OUTLINE:
Patients receive bevacizumab IV over 30-90 minutes on day 1 in weeks 1, 3, 5, 7, 9, and 11. Patients also receive interleukin-2 subcutaneously on days 1-5 in weeks 5-10. Treatment repeats every 12 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease then receive bevacizumab alone in weeks 1, 3, 5, 7, 9, and 11. Courses with bevacizumab alone repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically or cytologically confirmed renal cell cancer
- •Metastatic disease
- •More than 75% clear cell histology
- •Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
- •No prior refractory disease, defined as clinical or radiologic progression, during or within 3 months after completion of prior interleukin-2 (IL-2)
- •Nominally "good" or "intermediate" risk disease, meeting ≥ 4 out of 5 of the following criteria:
- •Hemoglobin > 10 g/dL (except for patients with hereditary hemoglobinopathy)
- •ECOG performance status 0-1 (required)
- •Calcium normal (corrected)
- •Patients with hypercalcemia due to malignancy allowed provided it has been controlled for > 1 month
- •Primary tumor treated or resected by complete nephrectomy, partial nephrectomy, radiofrequency ablation, or other local ablation
- •Lactic dehydrogenase < 1.5 times upper limit of normal (ULN)
- •No history of or current brain or CNS metastasis by CT scan or MRI within the past 30 days
- •Performance status - ECOG 0-1
- •More than 4 months
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 75,000/mm^3
- •No history of bleeding diathesis
- •PTT < 1.5 times ULN
- •INR < 1.5
- •Bilirubin ≤ 1.5 times ULN
- •AST and ALT ≤ 2.5 times ULN
- •No chronic hepatitis B or C
- •Creatinine ≤ 2.0 mg/dL
- •No proteinuria* by dipstick urinalysis
- •Urine protein ≤ 1,000 mg by 24-hour urine collection
- •No symptomatic congestive heart failure
- •No uncontrolled hypertension, defined as systolic blood pressure (BP) > 160 mm Hg and diastolic BP > 90 mm Hg
- •No cardiac arrhythmia
- •No peripheral vascular disease ≥ grade 2
- •No clinically significant peripheral artery disease
- •None of the following arterial thromboembolic events within the past 6 months:
- •Transient ischemic attack
- •Cerebrovascular accident
- •Unstable angina pectoris
- •Myocardial infarction
- •Not pregnant
- •No nursing during and for 3 months after completion of study treatment
- •Negative pregnancy test
- •Fertile patients must use effective contraception before, during, and for 3 months after completion of study treatment
- •No active infection requiring parenteral antibiotics
- •No known HIV positivity
- •No history of allergic reaction to antibody drugs or IL-2
- •No psychiatric illness or social situation that would preclude study compliance
- •No non-healing wound or fracture
- •No insulin-dependent diabetes
- •No other uncontrolled illness
- •No other malignancy requiring active treatment within the past 2 years except nonmelanoma skin cancer
- •No prior bevacizumab
- •At least 6 months since prior immunotherapy containing IL-2
- +12 more not shown
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (bevacizumab, aldesleukin)
Patients receive bevacizumab IV over 30-90 minutes on day 1 in weeks 1, 3, 5, 7, 9, and 11. Patients also receive interleukin-2 subcutaneously on days 1-5 in weeks 5-10. Treatment repeats every 12 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease then receive bevacizumab alone in weeks 1, 3, 5, 7, 9, and 11. Courses with bevacizumab alone repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis (Other)
Treatment (bevacizumab, aldesleukin)
Patients receive bevacizumab IV over 30-90 minutes on day 1 in weeks 1, 3, 5, 7, 9, and 11. Patients also receive interleukin-2 subcutaneously on days 1-5 in weeks 5-10. Treatment repeats every 12 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease then receive bevacizumab alone in weeks 1, 3, 5, 7, 9, and 11. Courses with bevacizumab alone repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Bevacizumab (Biological)
Treatment (bevacizumab, aldesleukin)
Patients receive bevacizumab IV over 30-90 minutes on day 1 in weeks 1, 3, 5, 7, 9, and 11. Patients also receive interleukin-2 subcutaneously on days 1-5 in weeks 5-10. Treatment repeats every 12 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease then receive bevacizumab alone in weeks 1, 3, 5, 7, 9, and 11. Courses with bevacizumab alone repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Aldesleukin (Biological)
Outcomes
Primary Outcomes
Number of Evaluable Participants With Complete Response (CR) and Partial Response (PR) at One Year
Time Frame: 1 year
Major response according to Response Evaluation Criteria In Solid Tumors (RECIST). CR: Disappearance of all target lesions; Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Secondary Outcomes
- Number of Evaluable Participants With Overall Survival (OS) at 2 Years(2 years from start of treatment)
- Number of Evaluable Participants With Progression Free Survival (PFS)(Up to 2 years)
- Number of Participants With Possibly Related Serious Adverse Events (SAEs)(Up to 30 days after completion of treatment)
- Pearson Correlation Coefficients of Dendritic Cell (DC):Immature Cell (ImC) Ratio With DC Function(At baseline, at days 4-5, 9-10 (of course 1), and at the end of treatment)