Bevacizumab and Sunitinib in Treating Patients With Solid Tumors

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Other: laboratory biomarker analysis

Drug: sunitinib malate

Other: pharmacological study

Biological: bevacizumab

Study type

Interventional

Funder types

NIH

Identifiers

NCT00357318

U01CA062502 (U.S. NIH Grant/Contract)

CASE 5Y05 (Other Identifier)

7537 (Other Identifier)

P30CA043703 (U.S. NIH Grant/Contract)

NCI-2009-00185 (Registry Identifier)

CDR0000489184

Details and patient eligibility

About

This phase I trial is studying the side effects and best dose of bevacizumab and sunitinib in treating patients with solid tumors. 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. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and sunitinib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving bevacizumab together with sunitinib may kill more tumor cells.

Full description

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.

Enrollment

60 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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