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A Phase I Study of Bevacizumab in Combination With SU11248


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of Bevacizumab in Combination With SU11248


PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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
meningitis

- 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
vasculature

- 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
months."

- 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:

Interventional

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:

Yes

Principal Investigator

Brian Rini

Investigator Role:

Principal Investigator

Investigator Affiliation:

Case Western Reserve University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00185

NCT ID:

NCT00357318

Start Date:

June 2006

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific

Name

Location

Case Western Reserve UniversityCleveland, Ohio  44106