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A Phase I Study of Bevacizumab in Combination With SU11248

Phase 1
18 Years
Open (Enrolling)
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of Bevacizumab in Combination With SU11248


I. Determine the maximum tolerated dose of bevacizumab in combination with sunitinib malate
(SU11248) in patients with solid tumors.


I. Evaluate the objective response rate, time to disease progression, and overall survival
of these patients.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and oral sunitinib
malate (SU11248) once daily on days 1-28. Courses repeat every 42 days in the absence of
disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bevacizumab and SU11248 until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 10 patients are
treated at the MTD.

After completion of study therapy, patients are followed for 30 days.

Inclusion Criteria:

- Histologically proven metastatic/unresectable adrenocortical carcinoma or melanoma
not amenable to curative surgical or radiation therapy.

- Accrual closed as of 5/27/2009 to patients with renal cell carcinoma

- No squamous cell histology

- No histology in close proximity to a major blood vessel

- No history of or known brain metastases, spinal cord compression, or carcinomatous

- No new evidence of brain or leptomeningeal disease on screening CT scan or MRI

- ECOG performance status (PS) 0-1 OR Karnofsky PS 60-100%

- AST and ALT ≤ 2.5 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- Creatinine ≤ 1.5 times ULN

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥100,000/mm³

- Hemoglobin ≥ 10.0 g/dL

- Calcium ≤ 12.0 mg/dL

- Urine protein:creatinine ratio ≤ 0.5 by urinalysis

- Patients with urine protein:creatinine ratio > 0.5 must have proteinuria < 1,000 mg
by 24-hour urine collection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study therapy

- None of the following within the past 12 months:

- Myocardial infarction

- Severe/unstable angina

- Severe peripheral vascular disease (claudication) or procedure on peripheral

- Coronary/peripheral artery bypass graft

- New York Heart Association (NYHA) grade III-IV congestive heart failure

- Cerebrovascular accident or transient ischemic attack

- Clinically significant bleeding

- Deep venous thrombosis

- Pulmonary embolism

- No ongoing cardiac dysrhythmias of NCI CTCAE ≥ grade 2, atrial fibrillation of
any grade, or prolongation of the QTc interval to > 450 msec (males) or > 470
msec (females)

- No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or
ventricular fibrillation ≥ 3 beats in a row)

- No condition classified as NYHA grade III or IV

- No hypertension that cannot be controlled by medications

- Blood pressure < 140/90 mm Hg

- No evidence of bleeding diathesis or coagulopathy

- No history of abdominal fistula, gastrointestinal perforation, or
intra-abdominal abscess within the past 28 days

- No history of or known brain metastases, spinal cord compression or
carcinomatous meningitis, or new evidence of brain or leptomeningeal disease on
screening CT or MRI scan unless without progression on * MRI or CT for 3

- No significant traumatic injury within the past 28 days

- No serious, non-healing wound, ulcer, or bone fracture

- No known hypersensitivity to Chinese hamster ovary cell products or other
recombinant human antibodies

- No known HIV or AIDS-related illness

- No other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that would preclude study participation.

- Recovered from prior radiation therapy, surgery, or other prior therapy

- No prior bevacizumab or sunitinib malate (SU11248)

- Other antiangiogenic therapies allowed

- No prior tyrosine kinase inhibitor of the VEGF receptor or bevacizumab for patients
with metastatic renal cell carcinoma

- No major surgical procedures or open biopsy within the past 28 days

- No core biopsy within the past 7 days

- No radiation therapy or systemic therapy within the past 4 weeks

- No concurrent full-dose anticoagulants (e.g., warfarin)

- Concurrent low-dose anticoagulation (e.g., prophylactic port patency) allowed

- No concurrent treatment on another clinical trial

- No other concurrent investigational drugs

- No concurrent major surgery

- No other concurrent anticancer agents or therapies, including chemotherapy,
biological response modifiers, hormonal therapy, surgery, palliative radiation
therapy, or immunotherapy

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) of bevacizumab in combination with sunitinib malate determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)

Outcome Time Frame:

42 days

Safety Issue:


Principal Investigator

Brian Rini

Investigator Role:

Principal Investigator

Investigator Affiliation:

Case Western Reserve University


United States: Food and Drug Administration

Study ID:




Start Date:

June 2006

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific



Case Western Reserve University Cleveland, Ohio  44106