NCT00734890

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at P25-P50 for phase_1 lung-cancer

Timeline
Completed

Started Mar 2008

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2008

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

August 13, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 14, 2008

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2010

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2011

Completed
Last Updated

March 16, 2012

Status Verified

March 1, 2012

Enrollment Period

2.3 years

First QC Date

August 13, 2008

Last Update Submit

March 14, 2012

Conditions

Lung CancerLymphomaLymphoproliferative DisorderSmall Intestine CancerUnspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specificAIDS-related diffuse large cell lymphomaAIDS-related diffuse mixed cell lymphomaAIDS-related diffuse small cleaved cell lymphomaAIDS-related immunoblastic large cell lymphomaAIDS-related lymphoblastic lymphomaAIDS-related peripheral/systemic lymphomaAIDS-related small noncleaved cell lymphomaHIV-associated Hodgkin lymphomarecurrent adult Burkitt lymphomarecurrent adult diffuse large cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent adult grade III lymphomatoid granulomatosisrecurrent adult Hodgkin lymphomarecurrent adult immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent adult T-cell leukemia/lymphomarecurrent cutaneous T-cell non-Hodgkin lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent mantle cell lymphomarecurrent marginal zone lymphomarecurrent small lymphocytic lymphomaanaplastic large cell lymphomaangioimmunoblastic T-cell lymphomarecurrent mycosis fungoides/Sezary syndromeadult nasal type extranodal NK/T-cell lymphomaWaldenström macroglobulinemiaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomasplenic marginal zone lymphomaintraocular lymphomapost-transplant lymphoproliferative disordercutaneous B-cell non-Hodgkin lymphomasmall intestine lymphomaadenocarcinoma of the lungbronchoalveolar cell lung cancerlarge cell lung canceradenosquamous cell lung cancerrecurrent non-small cell lung cancerstage IIIA non-small cell lung cancerstage IIIB non-small cell lung cancerstage IV non-small cell lung cancerstage III adult Burkitt lymphomastage III adult diffuse large cell lymphomastage III adult diffuse mixed cell lymphomastage III adult diffuse small cleaved cell lymphomastage III adult Hodgkin lymphomastage III adult immunoblastic large cell lymphomastage III adult lymphoblastic lymphomastage III adult T-cell leukemia/lymphomastage III cutaneous T-cell non-Hodgkin lymphomastage III grade 1 follicular lymphomastage III grade 2 follicular lymphomastage III grade 3 follicular lymphomastage III mantle cell lymphomastage III marginal zone lymphomastage III mycosis fungoides/Sezary syndromestage III small lymphocytic lymphomastage IV adult Burkitt lymphomastage IV adult diffuse large cell lymphomastage IV adult diffuse mixed cell lymphomastage IV adult diffuse small cleaved cell lymphomastage IV adult Hodgkin lymphomastage IV adult immunoblastic large cell lymphomastage IV adult lymphoblastic lymphomastage IV adult T-cell leukemia/lymphomastage IV cutaneous T-cell non-Hodgkin lymphomastage IV grade 1 follicular lymphomastage IV grade 2 follicular lymphomastage IV grade 3 follicular lymphomastage IV mantle cell lymphomastage IV marginal zone lymphomastage IV mycosis fungoides/Sezary syndromestage IV small lymphocytic lymphoma

Outcome Measures

Primary Outcomes (3)

  • Maximum tolerated dose

  • Safety

  • Toxicity

Interventions

bevacizumabBIOLOGICAL
vandetanibDRUG
laboratory biomarker analysisOTHER
pharmacological studyOTHER

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (1)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

Related Publications (1)

  • 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.

    PMID: 21247755RESULT

MeSH Terms

Conditions

Lung NeoplasmsLymphomaLymphoproliferative DisordersBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinHodgkin DiseaseLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor T-Cell Lymphoblastic Leukemia-LymphomaLymphoma, T-Cell, CutaneousLymphoma, FollicularLymphoma, Mantle-CellLymphoma, B-Cell, Marginal ZoneLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyMycosis FungoidesSezary SyndromeLymphoma, Extranodal NK-T-CellWaldenstrom MacroglobulinemiaIntraocular LymphomaAdenocarcinoma of LungAdenocarcinoma, Bronchiolo-AlveolarCarcinoma, Non-Small-Cell Lung

Interventions

Bevacizumabvandetanib

Condition Hierarchy (Ancestors)

Respiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesNeoplasms by Histologic TypeLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesLymphoma, T-CellLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphadenopathyNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersEye NeoplasmsAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialCarcinoma, BronchogenicBronchial Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Shivaani Kummar, MD

    NCI - Medical Oncology Branch

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Purpose
TREATMENT
Sponsor Type
NIH

Study Record Dates

First Submitted

August 13, 2008

First Posted

August 14, 2008

Study Start

March 1, 2008

Primary Completion

June 1, 2010

Study Completion

February 1, 2011

Last Updated

March 16, 2012

Record last verified: 2012-03

Locations

US(1)