Sunitinib Malate and Bevacizumab in Treating Patients With Kidney Cancer or Advanced Solid Malignancies

NCT01243359 | Completed Phase 1

• 8 other identifiers: NCI-2013-00764CDR0000688559WCCC-CO-099048477CO 09904P30CA014520U01CA070095U01CA062491
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and the best dose of sunitinib malate when given together with bevacizumab in treating patients with kidney cancer or advanced solid malignancies. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Giving sunitinib malate together with bevacizumab may kill more tumor cells.

Conditions

Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Cancer; Stage I Renal Cell Cancer; Stage II Renal Cell Cancer; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• Proportion of patients with grade 3 or higher toxicities and recommended phase II dose of sunitinib in the presence of bevacizumab or sunitinib alone graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  6 weeks

• Objective response rate using the Response Evaluation Criteria in Solid Tumors (RECIST)

  Responses will be summarized using descriptive statistics and frequency tables. Two-sided 95% confidence intervals for the proportions of subjects with a confirmed anti-tumor response will be computed for the two treatment schedules of sunitinib malate

  Up to 2 years

Secondary Outcomes (2)

• Pharmacodynamic change in SUV peak and tumor perfusion using FLT PET/CT

  Baseline, at 4 weeks and 6 weeks of course 1

• Changes in the ration of free-bound plasma VEGF by Enzyme-linked immuno sorbent assay (ELISA)

  Baseline to 2 years

Study Arms (1)

Treatment (sunitinib malate, bevacizumab)

EXPERIMENTAL

Patients receive sunitinib malate PO on days 1-28 and bevacizumab IV over 30-90 minutes on day 29. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Drug: sunitinib malate; Biological: bevacizumab; Other: pharmacological study; Other: laboratory biomarker analysis; Other: fluorine F 18 fluorothymidine; Procedure: positron emission tomography; Procedure: computed tomography

Interventions

sunitinib malate DRUG

Given PO

Also known as: SU11248, sunitinib, Sutent

Treatment (sunitinib malate, bevacizumab)

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Treatment (sunitinib malate, bevacizumab)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (sunitinib malate, bevacizumab)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (sunitinib malate, bevacizumab)

fluorine F 18 fluorothymidine OTHER

Undergo FLT PET/CT

Also known as: 18F-FLT, 3'-deoxy-3'-[18F]fluorothymidine, fluorothymidine F-18

Treatment (sunitinib malate, bevacizumab)

positron emission tomography PROCEDURE

Undergo FLT PET/CT

Also known as: FDG-PET, PET, PET scan, tomography, emission computed

Treatment (sunitinib malate, bevacizumab)

computed tomography PROCEDURE

Undergo FLT PET/CT

Also known as: tomography, computed

Treatment (sunitinib malate, bevacizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed renal cell; or other solid malignancy (excluding lymphoma) that is metastatic or unresectable and for which no standard curative therapy exists; for the renal cell cancer subset, a component of clear cell histology is required (a minimum of 6 subjects with clear cell kidney cancer will be enrolled per treatment stratification; additional subjects enrolled per imaging cohort will allow "other" solid tumors)
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 2 times the slice width with spiral CT scan (i.e. 10 mm if the CT slice width is 5 mm, 14 mm if the CT slice width is 7 mm)
• Life expectancy of greater than 12 weeks
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL
• Serum calcium =\< 12.0 mg/dL
• Total serum bilirubin within normal institutional limits
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]))/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal, unless subjects have liver metastases, in which case both AST and ALT must be =\< 5 × institutional upper limit of normal
• Creatinine =\< 1.5 x normal institutional limits OR
• Creatinine clearance (measured) \>= 50 mL/min/1.73m\^2 for patients with creatinine levels above 1.5 x normal institutional limits
• Urine protein should be screened by urine analysis for urine protein creatinine (UPC) ratio; for a UPC ratio \> 0.5, a 24-hour urine protein should be obtained and the level should be \< 1,000 mg for eligibility; Note: UPC ratio of spot urine is an estimation of the 24 hour urine protein excretion; A UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gram; UPC ratio is calculated by the following formula:
• \[urine protein\]/\[urine creatinine\] (if both urine protein and creatinine reported as mg/dL)
• \[(urine protein) x 0.088\]/\[urine creatinine\] (if urine creatinine is reported in mmol/L)

You may not qualify if:

• Patients who have had chemotherapy, radiotherapy, experimental therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered (to grade =\< 1 or baseline) from clinically significant adverse events due to agents administered more than 4 weeks earlier (alopecia excluded); clinical significance to be determined by investigator
• Patients may not be receiving any other investigational agents
• Patients who have received prior treatment with any other VEGF signaling pathway inhibitors (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, PTK787, VEGF Trap, etc.) are ineligible
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib or bevacizumab
• Patients with QTc prolongation (defined as a QTc interval greater than or equal to 500 msec) or other significant electrocardiogram (ECG) abnormalities (per investigator discretion) are excluded
• Patients who require use of therapeutic doses of Coumarin-derivative anticoagulants such as warfarin are excluded, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis; Note: full-dose low-molecular weight heparin (or other blood thinners) will be excluded as well given potential for bleeding with this regimen; prophylactic doses of low-molecular weight heparin (LMWH) will be allowed if prothrombin time (PT)/international normalized ratio (INR) is =\< 1.5
• Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain sunitinib tablets are excluded
• Patients must have blood pressure (BP) no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility; initiation or adjustment of BP medication is permitted prior to study entry provided that the average of three BP readings at a visit prior to enrollment is less than 140/90 mmHg
• Patients with clinically significant cardiovascular disease are excluded
• Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry
• History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry
• Serious and inadequately controlled cardiac arrhythmia
• Significant vascular disease (e.g. aortic aneurysm, history of aortic dissection)
• Clinically significant peripheral vascular disease
• History of pulmonary embolism within the past 12 months

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Sunitinib; Bevacizumab; alovudine; Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Glenn Liu

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2010
• First Posted: November 18, 2010
• Study Start: October 1, 2010
• Primary Completion: February 1, 2014
• Last Updated: April 2, 2014

Record last verified: 2013-10

Locations

US (2)