Sorafenib and Bevacizumab to Treat Ovarian, Fallopian and Peritoneal Cancer

NCT ID: NCT00436215

Last Updated: 2020-11-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-12
• Study Completion Date: 2014-09-27

Brief Summary

Background:

• Sorafenib and bevacizumab are anti-cancer drugs that work by targeting the blood vessels that allow tumors to grow. Using the two drugs together may more effectively block the formation of blood vessels that feed tumors.
• Sorafenib and bevacizumab both are approved by the Food and Drug Administration for use in other cancers but have not ovarian cancer. In a preliminary trial of this drug combination, however, tumors in 6 of 14 patients with ovarian cancer shrank.

Objectives:

• To determine the safety and activity of the combination of sorafenib and bevacizumab for treating patients with ovarian, fallopian and peritoneal cancer.
• To determine how sorafenib and bevacizumab may affect the cancer by measuring amounts of different proteins in small biopsy samples of tumor taken before starting treatment and after 6 weeks.

Eligibility:

• Females 18 years of age and older with ovarian, fallopian, or peritoneal cancer whose disease has not responded to standard treatment or for which no standard treatment is available.
• Patients must have not been previously treated with bevacizumab or must have had their disease worsen while taking bevacizumab-based therapy.

Design:

• Patients take 200 mg of sorafenib by mouth twice a day Monday through Friday each week and 5 mg/kg of bevacizumab through a vein every 2 weeks.
• Tumor biopsies and imaging scans (magnetic resonance imaging (MRI) and positron emission tomography (PET) are done before treatment, 3 days after beginning treatment, and 6 weeks into therapy.
• Computed tomography (CT) or other imaging tests are done every 8 weeks to evaluate response to treatment.
• History, physical examinations, blood and urine tests are done periodically during treatment for health checks and research purposes.
• About 74 patients are to be enrolled in the trial.

Detailed Description

Background:

Sorafenib is an inhibitor of wild-type and mutant proto-oncogene BRaf (B-Raf) and proto-oncogene c-Raf (c-Raf) kinase isoforms in vitro, but it also inhibits mitogen-activated protein kinase (p38), proto-oncogene c-kit (c-kit), vascular endothelial growth factor receptor 2 (VEGFR-2) and platelet-derived growth factor (PDGFR)-Beta affecting tumor growth as well as possibly promoting apoptosis by events downstream of c-Raf.

Bevacizumab is a humanized immunoglobulin G 1 (IgG1) monoclonal antibody (MAb) that binds all biologically active isoforms of human vascular endothelial growth factor (vascular endothelial growth factor (VEGF), or VEGF-A) with high affinity (kd = 1.1nM).

Phase I trial of sorafenib and bevacizumab administered concurrently showed activity of the combination in patients with refractory ovarian cancer.

Objectives:

Determine the activity and tolerability of the combination bevacizumab and sorafenib in patients with refractory or recurrent epithelial ovarian, fallopian, or peritoneal cancer in patients who are bevacizumab-naive or bevacizumab-resistant.

Eligibility:

Adults with histologically documented refractory or recurrent epithelial ovarian, fallopian, or peritoneal cancer.

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

Patients must have an Eastern Cooperative Oncology Group (ECOG) of 1 or less.

Patients must have disease that is amenable to biopsy.

Patients must have not been previously treated with bevacizumab or must have progressed on prior bevacizumab-based therapy.

Design:

Patients will be stratified on entrance to the trial based on their previous exposure to bevacizumab to either strata A (bevacizumab-naive patients) or strata B (patients previously treated with bevacizumab).

Patients will receive oral sorafenib 200 mg twice daily 5 out of 7 days each week and intravenous bevacizumab 5 mg/kg every two weeks.

Tumor biopsies will be obtained from patients before treatment and six weeks into therapy. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fludeoxyglucose 18F-positron emission tomography (FDG-PET) will be obtained from patients before treatment, on day 3 of treatment, and six weeks into therapy.

Patients will be evaluated for response every 8 weeks using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

Approximately 74 patients will be needed to achieve the objectives of the trial.

Conditions

Ovarian Neoplasm; Fallopian Tube Cancer; Primary Peritoneal Cancer

Keywords

Sorafenib; Ovarian Cancer; Fallopian Cancer; Bevacizumab; Peritoneal Cancer; Fallopian Tube Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BAY 43-9006 + Bevacizumab

BAY 43-9006 (sorafenib) + Bevacizumab

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

bevacizumab 5 mg/kg intravenous (IV) every two weeks

BAY 43-9006

Intervention Type: DRUG

BAY 43-9006 200 mg po (by mouth) twice daily 5 out of 7 days each week (Mon-Fri)

Interventions

Bevacizumab

bevacizumab 5 mg/kg intravenous (IV) every two weeks

Intervention Type: DRUG

BAY 43-9006

BAY 43-9006 200 mg po (by mouth) twice daily 5 out of 7 days each week (Mon-Fri)

Intervention Type: DRUG

Other Intervention Names

Avastin; sorafenib

Eligibility Criteria

Exclusion Criteria

There is no limit on the number of prior regimens with which a patient has been treated.

Patients who have been treated with bevacizumab previously are eligible for the trial if they have progressed while on bevacizumab-based therapy.

-Disease progression on bevacizumab therapy will be defined as documented increase in disease based on imaging while the patient is receiving bevacizumab or within three months of their last dose of bevacizumab.

Patients must be at least 6 weeks from their last dose of bevacizumab prior to being enrolled on study.

Patients who have a healed fistula greater than 28 days prior to enrollment are eligible (refer to section 3.2.15 for patients who have had prior bevacizumab)

Serious non-healing wounds (including wounds healing by secondary intention), acute or non-healing ulcers, or bone fractures within 3 months of enrollment.

Moderate or massive hemoptysis or surgery within 28 days of enrollment.

Ongoing treatment with any other investigational agents.

Brain metastases

• Patients with central nervous system (CNS) metastases within the past 2 years are ineligible. Patients who have had CNS disease curatively treated and without recurrence for 2 years may be eligible. but any CNS disease that has not undergone curative therapy with radiation, gamma knife, and/or surgical therapy are ineligible.
• CNS imaging will not be mandated for all patients. However, if there is clinical suspicion of CNS involvement, a contrast computed tomography (CT) or magnetic resonance imaging (MRI) of the brain will be required.
• Patients with CNS metastases may not be on steroids for the purpose of CNS disease or edema control.
• Patients with CNS disease must be on an anti-seizure medication and that medication cannot be a CYPP4503A modulating agent.

Thrombotic or embolic events within the past 6 months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism, unstable angina, or myocardial infarction. Fully treated deep vein thrombosis no longer requiring anticoagulation will be allowed.

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (American Heart Association (AHA) Class II or worse), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

-Patients with evidence of active infection will become eligible for reconsideration 7 days after completing antibiotic therapy.

Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with sorafenib, bevacizumab, and/or the combination.

Hypertension defined as systolic blood pressure greater than 150 mmHg or diastolic pressure greater than 90 mmHg despite optimal medical management.

Therapeutic anticoagulation with coumadin, heparins, or heparinoids.

Evidence of a bleeding diathesis.

History of high grade varices or arteriovenous malformations.

Patients previously treated with sorafenib will not be eligible for this trial.

Fistula or bowel obstruction or perforation in the 28 days prior to enrollment.

Patients must not be taking the cytochrome p450 (CYP450) enzyme-inducing drugs phenytoin, carbamazepine, phenobarbital, St. John's wort, or rifampin.

For patients who have been previously treated with bevacizumab, any severe toxicity associated with bevacizumab while the patient was being treated with the agent will make the patient ineligible for the trial. This includes bevacizumab-induced hypertensive crisis, arterial thromboembolic events (including cardiac ischemia or cerebrovascular ischemia or other arterial thrombosis), nephrotic syndrome, gastrointestinal perforation, serious hemorrhage, and fistulas (unless the fistula completely resolved while the patient was still on bevacizumab or it has been surgically corrected).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Christina Annunziata, M.D.

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christina M Annunziata, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Countries

United States

References

Singer G, Oldt R 3rd, Cohen Y, Wang BG, Sidransky D, Kurman RJ, Shih IeM. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst. 2003 Mar 19;95(6):484-6. doi: 10.1093/jnci/95.6.484.

Reference Type: BACKGROUND

PMID: 12644542 (View on PubMed)

Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, Beller U, Westra WH, Ladenson PW, Sidransky D. BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst. 2003 Apr 16;95(8):625-7. doi: 10.1093/jnci/95.8.625.

Reference Type: BACKGROUND

PMID: 12697856 (View on PubMed)

Pollock PM, Meltzer PS. A genome-based strategy uncovers frequent BRAF mutations in melanoma. Cancer Cell. 2002 Jul;2(1):5-7. doi: 10.1016/s1535-6108(02)00089-2.

Reference Type: BACKGROUND

PMID: 12150818 (View on PubMed)

Lee JM, Annunziata CM, Hays JL, Cao L, Choyke P, Yu M, An D, Turkbey IB, Minasian LM, Steinberg SM, Chen H, Wright J, Kohn EC. Phase II trial of bevacizumab and sorafenib in recurrent ovarian cancer patients with or without prior-bevacizumab treatment. Gynecol Oncol. 2020 Oct;159(1):88-94. doi: 10.1016/j.ygyno.2020.07.031. Epub 2020 Aug 1.

Reference Type: RESULT

PMID: 32747013 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2007-C-0058.html

NIH Clinical Center Detailed Web Page

Other Identifiers

07-C-0058

Identifier Type: -

Identifier Source: secondary_id

070058

Identifier Type: -

Identifier Source: org_study_id