Bevacizumab and Sunitinib in Treating Patients With Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00357318
First received: July 26, 2006
Last updated: February 21, 2014
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: sunitinib malate
Biological: bevacizumab
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Bevacizumab in Combination With SU11248

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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) [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Objective response rate assessed by RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will be summarized using the method of Kaplan and Meier. 95% confidence intervals will be reported when appropriate.

  • Progression-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will be summarized using the method of Kaplan and Meier. 95% confidence intervals will be reported when appropriate.


Enrollment: 60
Study Start Date: June 2006
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (sunitinib malate, bevacizumab)
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.
Drug: sunitinib malate
Given PO
Other Names:
  • SU11248
  • sunitinib
  • Sutent
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357318

Locations
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Investigators
Principal Investigator: Brian Rini Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00357318     History of Changes
Other Study ID Numbers: NCI-2009-00185, NCI-2009-00185, CDR0000489184, CASE 5Y05, 7537, P30CA043703, U01CA062502
Study First Received: July 26, 2006
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bevacizumab
Sunitinib
Antibodies
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunologic Factors

ClinicalTrials.gov processed this record on September 22, 2014