Clinical trial NCT00126490: Bevacizumab and Interleukin-2 in Treating Patients With Metastatic Kidney Cancer
Official title: Phase 2 Trial of Sequential Bevacizumab Then Subcutaneous Interleukin-2 in Metastatic Renal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Renal Cell Carcinoma
Stage IV Renal Cell Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-08-04
Enrollment: 19
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 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.

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.

Eligibility 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

Primary outcomes:
measure: Number of Evaluable Participants With Complete Response (CR) and Partial Response (PR) at One Year
timeFrame: 1 year
Secondary outcomes:
measure: Number of Evaluable Participants With Overall Survival (OS) at 2 Years
timeFrame: 2 years from start of treatment
measure: Number of Evaluable Participants With Progression Free Survival (PFS)
timeFrame: Up to 2 years
measure: Pearson Correlation Coefficients of Dendritic Cell (DC):Immature Cell (ImC) Ratio With DC Function
timeFrame: At baseline, at days 4-5, 9-10 (of course 1), and at the end of treatment
measure: Number of Participants With Possibly Related Serious Adverse Events (SAEs)
timeFrame: Up to 30 days after completion of treatment
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
Study officials:
affiliation: Moffitt Cancer Center
name: Mayer Fishman
role: PRINCIPAL_INVESTIGATOR
References: