Sorafenib and Bevacizumab to Treat Ovarian, Fallopian and Peritoneal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Christina Annunziata, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00436215
First received: February 15, 2007
Last updated: October 7, 2015
Last verified: October 2015
  Purpose

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.

Condition Intervention Phase
Ovarian Neoplasm
Fallopian Tube Cancer
Primary Peritoneal Cancer
Drug: Bevacizumab
Drug: BAY 43-9006
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Sorafenib and Bevacizumab in Epithelial Ovarian, Fallopian, and Peritoneal Cancer

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Clinical Response Rate. [ Time Frame: patients were followed for a median of 18 weeks (range 1-116 weeks) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression-free Survival [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]
    Progression free survival is defined by the number of weeks between the first day of treatment and the date of cancer progression.

  • Number of Participants With Adverse Events [ Time Frame: up to 28 months ] [ Designated as safety issue: Yes ]
    Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.


Enrollment: 55
Study Start Date: December 2006
Study Completion Date: September 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BAY 43-9006 + Bevacizumab
BAY 43-9006 (sorafenib) + Bevacizumab
Drug: Bevacizumab
bevacizumab 5 mg/kg intravenous (IV) every two weeks
Drug: BAY 43-9006
BAY 43-9006 200 mg po (by mouth) twice daily 5 out of 7 days each week (Mon-Fri)
Other Name: sorafenib

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • ELIGIBILITY CRITERIA:

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).

-Recurrent/refractory disease defined as progression within 6 months of upfront platinum-containing therapy or progression after subsequent therapy in previously relapsed patients.

Disease amenable to percutaneous or skin biopsy as determined by an associate investigator and a member of the interventional team.

Patient willingness to have biopsies performed.

Measurable disease defined as tumor greater than or equal to 1 cm.

Age greater than or equal to 18 years.

Life expectancy of more than 3 months.

Performance status of 0 to 1 according to the Eastern Cooperative Oncology Group (ECOG) criteria.

Adequate organ function as defined below:

Laboratory Test Required value

  • Leukocytes greater than or equal to 3,000/ microliter
  • Absolute neutrophil count greater than or equal to 1,200/ microliter
  • Platelets greater than or equal to 100,000/ microliter
  • Total bilirubin less than or equal to 1.5 times the institutional upper limits of normal
  • Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5 times the institutional upper limit of normal
  • Creatinine less than or equal to 1.5 mg/dL

OR

  • Creatinine clearance greater than or equal to 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.
  • Activated partial thromboplastin time (PTT) less than 1.5 times the institutional upper limits of normal
  • Prothrombin Time (PT)/ International normalized ratio (INR) less than 1.5 times the institutional upper limits of normal
  • Amylase and Lipase Less than institutional upper limits of normal

Patients must have a urine protein/creatinine ratio (UPC) less than 1.0 for enrollment.

No surgery, radiation therapy, chemotherapy, immunotherapy, biotherapy, or hormonal therapy (exception raloxifene for bone health) within four weeks (6 weeks for mitomycin C, carboplatin, or nitrosoureas);

No metabolically active complimentary or alternative therapy for at least 1 week, defined as any ingested or administered chemical substances including herbal medications, but not including acupuncture, hypnosis, meditation, or other non-chemical treatments.

No monoclonal antibody therapy for at least 6 weeks.

Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be less than or equal to grade 1 (as defined by Common Terminology Criteria for Adverse Events (CTCAE v3) or returned to baseline. Peripheral neuropathy less than or equal to grade 2 will be allowed as this patient population has universally been treated with platinum-based chemotherapy with residual neuropathy being a common occurrence.

No other invasive malignancies within the past two years (with the exception of non-melanoma skin cancers, non-invasive bladder cancer, stage I endometrial cancer or cervical cancer synchronous to the ovarian cancer diagnosis and cured by surgical resection).

Ability to understand and sign an informed consent form.

Patients who require hematopoietic growth factor support (e.g. epogen, darbepoetin), Non-steroidal anti-inflammatory drugs (NSAIDs), and other maintenance medications prior to study entry will be allowed to continue their supportive therapies.

Ability to tolerate orally administered medications.

Contraception is not a consideration as these patients have all had surgical removal of their reproductive organs. Pregnant women are excluded from this study because BAY 43-9006 and bevacizumab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BAY 43-9006 and/or bevacizumab, breastfeeding should be discontinued if the mother is treated with BAY 43-9006 and/or bevacizumab.

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)

EXCLUSION CRITERIA:

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).

  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: NCT00436215

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Christina M Annunziata, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: Christina Annunziata, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00436215     History of Changes
Other Study ID Numbers: 070058  07-C-0058 
Study First Received: February 15, 2007
Results First Received: March 16, 2015
Last Updated: October 7, 2015
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Sorafenib
Ovarian Cancer
Fallopian Cancer
Bevacizumab
Peritoneal Cancer
Fallopian Tube Cancer

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Ovarian Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders
Bevacizumab
Sorafenib
Niacinamide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2016