Protocol Number: 05-C-0022

Title:

A Phase I Trial of BAY 43-9006 (Sorafenib) and Bevacizumab in Refractory Solid Tumors with Biologic and Proteomic Analysis

Number:

05-C-0022

Summary:

Background:

-BAY 43-9006 is an inhibitor of wild-type and mutant B-Raf and c-Raf kinase isoforms in vitro, but it also inhibits p38, c-kit, VEGFR-2 and PDGFR-Beta affecting tumor growth as well as possibly promoting apoptosis by events downstream of c-Raf.

-Bevacizumab is a humanized IgG1 monoclonal antibody (MAb) that binds all biologically active isoforms of human vascular endothelial growth factor (VEGF, or VEGF-A) with high affinity (k(d)= 1.1nM)

-The most common adverse events associated with bevacizumab of any severity include asthenia, pain, headache, hypertension, diarrhea, stomatitis, constipation, epistaxis, dyspnea, dermatitis and proteinuria.

-This Phase I trial is open to patients with all solid tumors.

Objectives:

-Determine the safety and toxicity of the combination of BAY 43-9006 (Sorafenib) and bevacizumab.

-Determine estimates of biochemical changes in the Ras-Raf-MAPK and VEGF signal transduction pathways in tumor and stromal cells in response to treatment at the MTD, at least in a pilot fashion, if those changes are statistically significant.

Eligibility:

-Adults with histologically documented solid tumor malignancy that is metastatic or unresectable and for which standard curative therapies do not exist or are no longer effective.

-Patients must be off prior chemotherapy, radiation therapy, hormonal therapy, or biological therapy for at least 4 weeks.

-All patients enrolling in cohort 2 must have at least one lesion amenable to biopsy.

-ECOG performance status 0 or 1 and adequate organ and marrow function.

Design:

-Cohort I will receive BAY 43-9006 and bevacizumab together at the start of study in a dose escalation fashion.

-Cohort II will be randomized as to which agent they receive for cycle one. Cycles 2 and beyond are treated using both agents.

-Tumor biopsies will be obtained from patients in Cohort II before treatment, two weeks into mono-therapy, and two weeks into combinatorial therapy.

-DCE-MRI studies will be obtained on patients in Cohort II before treatment, two weeks into monotherapy, four weeks into monotherapy, and two weeks into combinatorial therapy.

-FDG-PET studies will be obtained on patients in Cohort II before treatment, two weeks into mono-therapy, and two weeks into combinatorial therapy.

-Patients will be evaluated for toxicity in clinic every 2 weeks for Cycles 1 and 2, and then every 4 weeks.

-Patients will be evaluated for response every 8 weeks using the RECIST criteria.

-Approximately 62 patients will be needed to achieve the objectives of the trial.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: No longer recruiting/follow-up only

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Raf-Kinase Inhibitor

Combinatorial Therapy

Pathway Profiling

Angiogenesis

VEGFR

Recruitment Keyword(s):

Cancer

Solid Tumor

Metastatic Uresectable Solid Tumors

Condition(s):

Neoplasms

Investigational Drug(s):

None

Investigational Device(s):

None

Interventions:

Drug: Bevacizumab

Drug: BAY 43-9006

Supporting Site:

National Cancer Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Campbell SL, Khosravi-Far R, Rossman KL, Clark GJ, Der CJ. Increasing complexity of Ras signaling. Oncogene. 1998 Sep 17;17(11 Reviews):1395-413. Review.

Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, Beller U, Westra WH, Ladenson PW, Sidransky D. Free Full Text BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst. 2003 Apr 16;95(8):625-7.

Chong H, Vikis HG, Guan KL. Mechanisms of regulating the Raf kinase family. Cell Signal. 2003 May;15(5):463-9. Review.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department Clinical Research Informatics, CC.

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