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NeoplasmsPhase 1NCT00095459

BAY 43-9006 (Sorafenib) and Bevacizumab (Avastin) To Treat Solid Tumors

A Phase 1 study testing Bevacizumab and BAY 43-9006 in people with Neoplasms, 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
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms
What is being tested?
Bevacizumab and BAY 43-9006
How many people
57 participants
Where
1 siteUnited States
Study dates
2 Nov 2004to 20 Jul 2012
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Patients must have a solid tumor malignancy that is metastatic or unresectable and for which standard curative therapies do not exist or are no longer effective.
  • Patients must have histological documentation of cancer confirmed in the Laboratory of Pathology/NCI.
  • Patients must be off prior chemotherapy, radiation therapy, hormonal therapy, or biological therapy for at least 4 weeks. Patients who were receiving mitomycin C, nitrosoureas, or carboplatin must be 6 weeks from the last administration of chemotherapy. Patients with prostate cancer must continue to receive LHRH agonist (unless orchiectomy has been performed). Patients should not be receiving complementary/alternative therapy while on study. Furthermore, complementary therapy should be stopped at least 7 days prior to enrollment. Any patient who has undergone therapy with a monoclonal antibody must be at least 8 weeks from the last treatment.
  • All patients enrolling in cohort 2 must have at least one lesion amenable to biopsy. This determination will be made by a member of the interventional radiology team or surgical associate investigator and an associate investigator. This requirement is not necessary for patients in cohort 1.
  • Age greater than 18 years.
  • ECOG performance status 0 or 1.
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  • Life expectancy of greater than 3 months.
  • Patients must have adequate organ and marrow function as defined below:
  • Leukocytes greater than 3,000/microliter
  • Absolute neutrophil count greater than 1,200/microliter
  • Platelets greater than 100,000/microliter
  • Total Bilirubin less than or equal to 1.5 times the institutional upper limits of normal
  • AST(SGOT) and ALT(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 45 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
  • Activated partial thromboplastin time (PTT) less than 1.25 times the institutional upper limits of normal
  • Prothrombin Time (PT) OR INR less than 1.25 times the institutional upper limits of normal
  • Amylase and Lipase less than or equal to the institutional upper limit of normal
  • Spot Urine Protein Creatinine Ratio less than 0.5; If result is 0.5 or more, a 24-hour urine for protein excretion must be less than 1000mg
  • Patients must have recovered from toxicity related to prior therapy to at least CTEP grade 1 (defined by CTC 3.0). Chronic stable grade 2 peripheral neuropathy secondary to neurotoxicity from prior therapies may be considered on a case by case basis by the Principal Investigator.
  • Women of child-bearing potential and men must agree to use adequate contraception (abstinence; hormonal or barrier method of birth control) for the study and at least 2 months after completion. Pregnant women will not be eligible for study.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Brain metastases
  • Patients who have a history of remote CNS metastases that have undergone "curative therapy" by radiation therapy, gamma knife therapy, or surgery and have remained without recurrence for a period of greater than or equal to 2 years will be considered on a case-by-case basis.
  • CNS imaging will not be mandated for all patients. However, if there is clinical suspicion of CNS involvement, a contrast CT or MRI of the brain will be required. Screening CNS scans should be required for certain tumor types with relatively high risk of CNS metastases, including but not limited to melanoma, RCC, breast, lung.
  • 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.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (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.
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  • HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006, bevacizumab, and/or the combination.
  • Patients who have been treated with BAY 43-9006 or bevacizumab will be excluded
  • Hypertension defined as systolic blood pressure greater than 140 mmHg or diastolic pressure greater than 90 mmHg despite optimal medical management.
  • Proteinuria defined as a 24-hour urine protein excretion greater than 1000 mg. Spot urine analysis for protein creatinine ratio (UPC) of 0.5 or greater will require a 24-hour urine to determine eligibility for enrollment.
  • Therapeutic anticoagulation with coumadin, heparins, or heparinoids.
  • Serious non-healing wounds (including wounds healing by secondary intention), acute or non-healing ulcers, or bone fractures within 3 months of fracture. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abcesses within 28 days will be excluded.
  • Evidence of bleeding diathesis
  • Impairment of swallowing that would preclude administration of BAY 43-9006.
  • History of hemoptysis or surgery within the past 28 days.
  • Patients with squamous cell carcinoma of the lungs will be excluded due to risk of fatal pulmonary hemorrhage. If a patient has a history of any type primary lung cancer and hemoptysis, they will be excluded.
  • History of high grade varices.
  • Use of herbal supplements are not permitted within 14 days of trial commencement and on study. Vitamin supplement (above a typical single multi-vitamin) usage is discouraged unless clearly indicated by an existing medical condition. An Associate or Principal Investigator will have the discretion regarding which vitamin supplements are permitted.
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies.

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

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.
Read more

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.
Read the detailed description

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.
Conditions
Neoplasms
Being tested
Bevacizumab, BAY 43-9006
Keywords
Raf-Kinase Inhibitor, Combinatorial Therapy, Pathway Profiling, VEGFR, Bevacizumab, Sorafenib, Advanced Solid Tumors, Angiogenesis, Targeted Therapy, VEGF, Cancer, Solid Tumor, Metastatic Uresectable Solid Tumors
Medical subject headings
Neoplasms

What participants receive

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

Timeline

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

  1. First posted5 Nov 2004 (estimated)
  2. Study start2 Nov 2004
  3. Primary completion1 Nov 2005
  4. Study completion20 Jul 2012

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 1
Primary purpose
Treatment
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00095459
Sponsor's protocol ID
050022
Other IDs
05-C-0022
Status last verified
23 Apr 2014
First submitted
4 Nov 2004
Last updated
17 Dec 2019
Results posted
No

Publications

  • 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. doi: 10.1038/sj.onc.1202174.

    PubMed 9779987

  • 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

  • Chong H, Vikis HG, Guan KL. Mechanisms of regulating the Raf kinase family. Cell Signal. 2003 May;15(5):463-9. doi: 10.1016/s0898-6568(02)00139-0.

    PubMed 12639709

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bevacizumab and BAY 43-9006 in people with Neoplasms, 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 21 inclusion and 19 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 17 Dec 2019. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00095459, which also lists 3 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 17 Dec 2019.

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