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Ovarian NeoplasmPhase 2NCT00436215

Sorafenib and Bevacizumab to Treat Ovarian, Fallopian and Peritoneal Cancer

A Phase 2 study testing Bevacizumab and BAY 43-9006 in people with Ovarian Neoplasm and Fallopian Tube Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bevacizumab and BAY 43-9006
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
1 siteUnited States
Study dates
12 Dec 2006to 27 Sep 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • 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.
Show all 20Show fewer
  • 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).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Phase II Study of Sorafenib and Bevacizumab in Epithelial Ovarian, Fallopian, and Peritoneal Cancer

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.
Read more

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.
Read the 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.

Being tested
Bevacizumab, BAY 43-9006
Keywords
Sorafenib, Ovarian Cancer, Fallopian Cancer, Bevacizumab, Peritoneal Cancer, Fallopian Tube Cancer
Medical subject headings
Ovarian Neoplasms, Fallopian Tube Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabDrug

    Also called Avastin

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

  • BAY 43-9006Drug

    Also called sorafenib

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

Study groups in NCT00436215
Study groupRoleWhat they receive
BAY 43-9006 + BevacizumabExperimentalBAY 43-9006 (sorafenib) + Bevacizumab
Receives: Drug: Bevacizumab; Drug: BAY 43-9006

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (2)

  1. Progression-free Survival

    Progression free survival is defined by the number of weeks between the first day of treatment and the date of cancer progression.

    Measured: up to 28 months

  2. Number of Participants With Adverse Events

    Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

    Measured: up to 28 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2007 (estimated)
  2. Study start12 Dec 2006
  3. Primary completion26 Jun 2014
  4. Study completion27 Sep 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00436215
Sponsor's protocol ID
070058
Other IDs
07-C-0058
Status last verified
Nov 2020
First submitted
15 Feb 2007
Last updated
23 Nov 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 12644542

  • 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.

    PubMed 12697856

  • 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.

    PubMed 12150818

  • 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.

    PubMed 32747013

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab and BAY 43-9006 in people with Ovarian Neoplasm and Fallopian Tube Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Response Rate. (time frame: patients were followed for a median of 18 weeks (range 1-116 weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00436215, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2020.

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