Bevacizumab and Interleukin-2 in Treating Patients With Metastatic Kidney Cancer

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Stage IV Renal Cell Cancer

Recurrent Renal Cell Carcinoma

Treatments

Other: Laboratory Biomarker Analysis

Biological: Aldesleukin

Biological: Bevacizumab

Study type

Interventional

Funder types

NIH

Identifiers

NCT00126490

6438 (Other Identifier)

NCI-6438

NCI-2012-02663 (Registry Identifier)

MCC-IRB-102782

CDR0000434852

MCC 13921 (Other Identifier)

P30CA076292 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

After completion of study treatment, patients are followed at 30 days and then every 3 months for at least 2 years.

PROJECTED ACCRUAL: Approximately 10-38 patients will be accrued for this study within 21 months.

Enrollment

19 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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
At least 2 months since prior investigational antibodies
More than 4 weeks since prior conventional cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
No concurrent corticosteroids except replacement corticosteroids for adrenal insufficiency OR inhaled steroids for chronic obstructive pulmonary disease, asthma, or allergic rhinitis
More than 3 weeks since prior radiotherapy and recovered
No prior radiotherapy to the only site of measurable disease unless there has been subsequent disease progression
More than 4 weeks since prior major surgery
At least 24 hours since prior minor surgical procedure, placement of vascular access device, or fine needle aspiration
At least 30 days since prior and no other concurrent investigational agents
More than 10 days since prior anticoagulants
- Low-dose anticoagulants for maintenance of vascular access device patency allowed
No concurrent therapeutic warfarin, including warfarin for treatment of deep vein thrombosis or pulmonary embolism
No other concurrent anticancer therapy