Sorafenib and Bevacizumab to Treat Ovarian, Fallopian and Peritoneal Cancer

NCT00436215 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 07005807-C-0058
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Neoplasm; Fallopian Tube Cancer; Primary Peritoneal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Clinical Response Rate.

  Clinical response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions. PR is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease (PD) is a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started lasting at least 6 months.

  patients were followed for a median of 18 weeks (range 1-116 weeks)

Secondary Outcomes (2)

• Progression-free Survival

  up to 28 months

• Number of Participants With Adverse Events

  up to 28 months

Study Arms (1)

BAY 43-9006 + Bevacizumab

EXPERIMENTAL

BAY 43-9006 (sorafenib) + Bevacizumab

Drug: Bevacizumab; Drug: BAY 43-9006

Interventions

Bevacizumab DRUG

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

Also known as: Avastin

BAY 43-9006 + Bevacizumab

BAY 43-9006 DRUG

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

Also known as: sorafenib

BAY 43-9006 + Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Histopathologically documented recurrent/refractory epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer from a previous biopsy verified by the Laboratory of Pathology, National Cancer Institute (NCI).
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 12644542 BACKGROUND

• 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.

  PMID: 12697856 BACKGROUND

• 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.

  PMID: 12150818 BACKGROUND

• 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.

  PMID: 32747013 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

Bevacizumab; Sorafenib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Christina Annunziata
• Organization: National Cancer Institute

annunzic@mail.nih.gov

301-402-7189

Study Officials

• Christina M Annunziata, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 15, 2007
• First Posted: February 19, 2007
• Study Start: December 12, 2006
• Primary Completion: June 26, 2014
• Study Completion: September 27, 2014
• Last Updated: November 23, 2020
• Results First Posted: March 26, 2015

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)