Lung CancerPhase 1NCT00734890
Vandetanib and Bevacizumab in Treating Patients With Advanced Solid Tumors or Lymphoma
A Phase 1 study testing bevacizumab, vandetanib and laboratory biomarker analysis in people with Lung Cancer and Lymphoma, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial summary
RATIONALE: Vandetanib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Lymphoma, Lymphoproliferative Disorder
- What is being tested?
- bevacizumab, vandetanib and laboratory biomarker analysis
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2008to Feb 2011
- 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
DISEASE CHARACTERISTICS:
- Histologically confirmed advanced malignancy, including the following:
- Solid tumor that is refractory to standard therapy or for which no standard therapy exists
- No lung carcinoma of squamous cell or small cell histology (mixed tumors will be categorized by the predominant cell type)
- Histological confirmation based on sputum cytology alone is not acceptable
- Lymphoma (Hodgkin or non-Hodgkin lymphoma) that has progressed after standard therapy AND for which stem cell transplantation is not indicated or has been refused
- No known CNS disease, except for treated brain metastasis meeting the following criteria:
- No ongoing requirement for steroids
- No evidence of progression or hemorrhage by clinical examination and brain imaging (MRI or CT scan) for ≥ 3 months after treatment
- Stable dose of anticonvulsants allowed
- Prior treatment for brain metastases may have included whole-brain radiotherapy, radiosurgery (gamma knife, linear accelerator, or equivalent), or a combination of therapy as deemed appropriate by the treating physician
- Neurosurgical resection or brain biopsy for treatment of CNS metastases allowed provided treatment was completed more than 3 months ago
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Life expectancy > 3 months
- Absolute neutrophil count ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- Creatinine < 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
- Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg by 24-hour urine collection
- Activated partial thromboplastin time ≤ 1.5 times ULN
- Prothrombin time OR INR < 1.5 times ULN
- Potassium between 4 mmol/L and ULN (supplementation allowed)
- Magnesium normal (supplementation allowed)
- Serum calcium (adjusted for albumin) or ionized calcium normal (supplementation allowed)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
- HIV-positivity allowed provided the following criteria are met:
- Patient does not require anti-HIV therapy
- CD4 count > 350/mm^3
- HIV viral load < 25,000 copies/mm^3
- No history of opportunistic infections
- No evidence of severe or uncontrolled systemic disease or any concurrent condition that could compromise participation in the study, including any of the following:
- Active or uncontrolled infection
- Immune deficiencies
- HIV infection requiring anti-HIV therapy
- Hepatitis B
- Hepatitis C
- Uncontrolled diabetes
- Uncontrolled hypertension
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Myocardial infarction within the past 6 months
- Uncontrolled cardiac arrhythmia
- Stroke/cerebrovascular accident within the past 6 months
- Psychiatric illness/social situation that, in the investigator's opinion, would make it undesirable for the patient to participate in the study or that would jeopardize study compliance
- No New York Heart Association class III or IV heart disease within the past 6 months
- No history of arrhythmia (i.e., multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment
- Atrial fibrillation allowed provided it is controlled with medication
- No asymptomatic sustained ventricular tachycardia
- No other cardiac disease that, in the investigator's opinion, would increase the risk of ventricular arrhythmia
- QTc < 480 msec (with measurable Bazett correction) by screening ECG
- No history of QTc prolongation as a result of other medications that required discontinuation
- No congenital long QT syndrome
- No first-degree relative with unexplained sudden death at under 40 years of age
- No left bundle branch block
- No hypertension not controlled by medical therapy, defined as systolic blood pressure > 150 mm Hg or diastolic blood pressure > 90 mm Hg despite optimal medical management
- No other clinically significant cardiac event
- No thromboembolic disease within the past 6 months
- No significant vascular disease (e.g., aortic aneurysm or aortic dissection) or clinically significant peripheral vascular disease
- No serious non-healing wounds (including wounds healing by secondary intention)
- No acute or non-healing ulcers
- No bone fractures within the past 3 months
- No abdominal fistula, gastointestinal perforation, or intra-abdominal abscess within the past 28 days
- No currently active diarrhea that may affect the ability of the patient to absorb or tolerate vandetanib
- No hemoptysis (bright red blood of ≥ ½ teaspoon per episode) within the past 3 months
- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior anti-VEGF therapy allowed
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy and recovered
- More than 4 weeks since prior major surgery and recovered
- At least 2 weeks since prior investigational drugs given in a phase 0 clinical trial
- More than 10 days since prior and no concurrent aspirin (> 325 mg/day) or chronic use of other NSAIDs
- No concurrent regular, therapeutic anticoagulation
- No concurrent medication that may cause QTc prolongation, induce Torsades de Pointes, or induce CYP3A4 function, including any of the following:
- Rifampin
- Rifabutin
- Phenytoin
- Carbamazepine
- Phenobarbital
- Hypericum perforatum (St. John's wort)
- No other concurrent antineoplastic therapy, except for gonadotropin-releasing hormone therapy for prostate cancer
Trial locations and contacts
1 site in 1 country.
United States1 site
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, 20892-1182
About this study
Official title: Phase I Study of Vandetanib (ZD 6474) and Bevacizumab Combination Therapy Evaluating the VEGF and EGF Signal Transduction Pathways in Adults With Solid Tumors and Lymphomas
RATIONALE: Vandetanib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bevacizumab and vandetanib may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving vandetanib together with bevacizumab may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vandetanib and bevacizumab in treating patients with advanced solid tumors or lymphoma.
Read the detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose, safety, and toxicity of vandetanib and bevacizumab in patients with advanced solid tumors or lymphoma.
Secondary
- Characterize the pharmacokinetic profile of this regimen in these patients.
- Measure changes in VEGF and other angiogenic cytokines in plasma samples from these patients.
- Determine the biochemical changes in the EGF signal transduction pathways in tumor biopsy samples from these patients.
- Determine the anti-angiogenic effects of this regimen in tumor biopsy samples from these patients.
- Evaluate the application of dynamic contrast-enhanced MRI to determine early changes in tumor vascular permeability during treatment.
- Evaluate the effects of this regimen on circulating endothelial progenitors and mature circulating endothelial cells in these patients.
OUTLINE: Patients receive oral vandetanib once daily on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection periodically for correlative laboratory studies, including pharmacokinetic, biomarker (VEGF and other angiogenic cytokines), and circulating endothelial cell analysis. Patients may also undergo optional tumor biopsies for additional correlative laboratory studies.
- Conditions
- Lung Cancer, Lymphoma, Lymphoproliferative Disorder, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific
- Being tested
- bevacizumab, vandetanib, laboratory biomarker analysis, pharmacological study
- Keywords
- unspecified adult solid tumor, protocol specific, AIDS-related diffuse large cell lymphoma, AIDS-related diffuse mixed cell lymphoma, AIDS-related diffuse small cleaved cell lymphoma, AIDS-related immunoblastic large cell lymphoma, AIDS-related lymphoblastic lymphoma, AIDS-related peripheral/systemic lymphoma, AIDS-related small noncleaved cell lymphoma, HIV-associated Hodgkin lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis, recurrent adult Hodgkin lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult T-cell leukemia/lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent grade 1 follicular lymphoma
- Medical subject headings
- Lung Neoplasms, Lymphoma, Lymphoproliferative Disorders, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Hodgkin Disease, Lymphoma, Large-Cell, Immunoblastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabBiological
vandetanibDrug
laboratory biomarker analysisOther
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
Safety
Toxicity
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2008 (estimated)
- Study startMar 2008
- Primary completionJun 2010
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Shivaani Kummar, MD, Principal investigator, NCI - Medical Oncology Branch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00734890
- Sponsor's protocol ID
- 080087
- Other IDs
- 08-C-0087, NCI-P7189, CDR0000590152
- Status last verified
- Mar 2012
- First submitted
- 13 Aug 2008
- Last updated
- 16 Mar 2012
- Results posted
- No
Publications
Kummar S, Gutierrez ME, Chen A, Turkbey IB, Allen D, Horneffer YR, Juwara L, Cao L, Yu Y, Kim YS, Trepel J, Chen H, Choyke P, Melillo G, Murgo AJ, Collins J, Doroshow JH. Phase I trial of vandetanib and bevacizumab evaluating the VEGF and EGF signal transduction pathways in adults with solid tumours and lymphomas. Eur J Cancer. 2011 May;47(7):997-1005. doi: 10.1016/j.ejca.2010.12.016. Epub 2011 Jan 17.
PubMed 21247755
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Vandetanib (ZD 6474) and Bevacizumab Combination Therapy Evaluating the VEGF and EGF Signal Transduction Pathways in Adults With Solid Tumors and Lymphomas
- ClinicalTrials.gov ID
- NCT00734890
- Acronym / sponsor ID
- 080087
- Conditions
- Lung Cancer, Lymphoma, Lymphoproliferative Disorder, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific
- Keywords
- unspecified adult solid tumor, protocol specific, AIDS-related diffuse large cell lymphoma, AIDS-related diffuse mixed cell lymphoma, AIDS-related diffuse small cleaved cell lymphoma, AIDS-related immunoblastic large cell lymphoma, AIDS-related lymphoblastic lymphoma, AIDS-related peripheral/systemic lymphoma, AIDS-related small noncleaved cell lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2008
- Primary completion
- Jun 2010 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 14 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Vandetanib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bevacizumab and vandetanib may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving vandetanib together with bevacizumab may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vandetanib and bevacizumab in treating patients with advanced solid tumors or lymphoma.
Detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose, safety, and toxicity of vandetanib and bevacizumab in patients with advanced solid tumors or lymphoma.
Secondary
- Characterize the pharmacokinetic profile of this regimen in these patients.
- Measure changes in VEGF and other angiogenic cytokines in plasma samples from these patients.
- Determine the biochemical changes in the EGF signal transduction pathways in tumor biopsy samples from these patients.
- Determine the anti-angiogenic effects of this regimen in tumor biopsy samples from these patients.
- Evaluate the application of dynamic contrast-enhanced MRI to determine early changes in tumor vascular permeability during treatment.
- Evaluate the effects of this regimen on circulating endothelial progenitors and mature circulating endothelial cells in these patients.
OUTLINE: Patients receive oral vandetanib once daily on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection periodically for correlative laboratory studies, including pharmacokinetic, biomarker (VEGF and other angiogenic cytokines), and circulating endothelial cell analysis. Patients may also undergo optional tumor biopsies for additional correlative laboratory studies.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bevacizumab | Biological | – |
| vandetanib | Drug | – |
| laboratory biomarker analysis | Other | – |
| pharmacological study | Other | – |
Primary outcome
Maximum tolerated dose
Safety
Toxicity
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2012.
- Results publication: PubMed 21247755Kummar S, Gutierrez ME, Chen A, Turkbey IB, Allen D, Horneffer YR, Juwara L, Cao L, Yu Y, Kim YS, Trepel J, Chen H, Choyke P, Melillo G, Murgo AJ, Collins J, Doroshow JH. Phase I trial of vandetanib and bevacizumab evaluating the VEGF and EGF signal transduction pathways in adults with solid tumours and lymphomas. Eur J Cancer. 2011 May;47(7):997-1005. doi: 10.1016/j.ejca.2010.12.016. Epub 2011 Jan 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shivaani Kummar, MD principal investigator
NCI - Medical Oncology Branch
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bevacizumab, vandetanib and laboratory biomarker analysis in people with Lung Cancer and Lymphoma, run by National Institutes of Health Clinical Center (CC) 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?
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 16 Mar 2012. 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.
What does the primary outcome measure?
Maximum tolerated dose. The study lists 3 primary outcomes in all. 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 NCT00734890, which also lists 1 linked publication.
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 16 Mar 2012.