Tandutinib Plus Bevacizumab to Treat Recurrent Brain Tumors
A Phase 2 Trial of Tandutinib in Combination With Bevacizumab for Patients With Recurrent High-Grade Gliomas
2 other identifiers
interventional
42
1 country
1
Brief Summary
Background: In order to survive, brain tumors must have a network of blood vessels to supply it with oxygen and nutrients. The tumors produce substances that enable new blood vessels to form. Tandutinib and Bevacizumab are experimental drugs that may prevent new blood vessel formation and thereby slow or stop tumor growth in the brain. Objectives: To determine the safety and side effects of Tandutinib in combination with Bevacizumab in patients with brain tumors. To evaluate the response of brain tumors to treatment with Tandutinib and Bevacizumab. Eligibility: Patients 18 years of age and older with a malignant brain tumor for whom standard treatments (surgery, radiation and chemotherapy) are no longer effective. Design: Patients receive treatment in 4-week cycles as follows: Tandutinib by mouth twice a day every day and intravenous (through a vein) infusions of Bevacizumab over 90 minutes (or less if well tolerated) every 2 weeks. Treatment may continue for up to 1 year, and possibly longer, as long as there are no signs of tumor growth or serious treatment side effects. Patients are evaluated with magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography (PET) scans before starting treatment and then periodically to determine the response to treatment. Patients have physical and neurological examinations every 4 weeks and blood tests every 2 weeks. They complete quality of life questionnaires every 4 weeks.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Apr 2008
Typical duration for phase_2
1 active site
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
April 1, 2008
CompletedFirst Submitted
Initial submission to the registry
April 25, 2008
CompletedFirst Posted
Study publicly available on registry
April 28, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2011
CompletedResults Posted
Study results publicly available
August 31, 2012
CompletedNovember 5, 2015
October 1, 2015
3.2 years
April 25, 2008
July 30, 2012
October 13, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival at 6 Months
Percentage of participants with progression free survival at 6 months. Progression is defined as a 25% increase in the sum of all measurable lesions (or two largest lesions if too numerous) over the smallest sum observed (over baseline if no decrease), clear worsening of any evaluable disease, appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
6 months
Secondary Outcomes (1)
Number of Participants With Adverse Events
45 months
Study Arms (2)
Tandutinib & Bevacizumab in GBM Patients
EXPERIMENTALGBM (glioblastoma multiforme) Tandutinib 500 mg by mouth daily dose twice a day. Bevacizumab 10 mg/kg dose intravenous repeated once every 2 weeks.
Tandutinib & Bevacizumab in AG Patients
EXPERIMENTALAG (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed oligoastrocytoma, and malignant astrocytoma NOS (not otherwise specified)) Tandutinib 500 mg by mouth daily dose twice a day. Bevacizumab 10 mg/kg dose intravenous repeated once every 2 weeks.
Interventions
Bevacizumab 10 mg/kg dose intravenous repeated once every 2 weeks.
Tandutinib 500 mg by mouth daily dose twice a day.
Forty-five one-sentence questionnaire to assess health related quality of life in patients with brain cancer.
Eligibility Criteria
You may qualify if:
- Patients with histologically proven intracranial malignant glioma will be eligible for this protocol.
- Malignant glioma includes glioblastoma multiforme (GBM), gliosarcoma, anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified).
- Patients must have evidence for tumor progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
- This scan should be performed within 14 days prior to registration and on a fixed dose of steroids for at least 5 days.
- If the steroid dose is increased between the date of imaging and registration a new baseline MRI/CT is required.
- The same type of scan, i.e. MRI or CT must be used throughout the period of protocol treatment for tumor measurement.
- Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
- They have recovered from the effects of surgery.
- Residual disease following resection of recurrent tumor is not mandated for eligibility into the study.
- To best assess the extent of residual disease post-operatively, a CT/ MRI should be done:
- no later than 96 hours in the immediate post-operative period or
- at least 4 weeks post-operatively, and
- within 14 days of registration, and
- on a steroid dosage that has been stable for at least 5 days.
- If the 96 hour scan is more than 21 days before registration, the scan needs to be repeated.
- +14 more criteria
You may not qualify if:
- Patients who, in the view of the treating physician, have significant active cardiac, hepatic, renal, or psychiatric diseases are ineligible.
- No concurrent use of other standard chemotherapeutics or investigative agents.
- Patients known to have a malignancy that has required treatment in the last 12 months and/or is expected to require treatment in the next 12 months (except non-melanoma skin cancer or carcinoma in-situ in the cervix).
- Patients who have an active infection.
- Pregnant (positive pregnancy test) or nursing women. Fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 6 months after the completion of tandutinib plus bevacizumab therapy.
- Patients who have any disease that will obscure toxicity (i.e. vasculitis, congenital hypercoaguability syndromes, uncontrolled primary hypertension, idiopathic thrombocytopenia).
- Evidence of significant recent hemorrhage on mandatory CT scan (defined as 1 cm or more of acute blood) of the brain within 7 days of patient accrual with the following exceptions: resolving hemorrhagic changes related to surgery, and/or presence of punctate hemorrhages in the tumor.
- Concurrent anti-coagulation or anti-platelet medication (including aspirin, non-steroidal anti-inflammatories, cyclooxygenase -2 (COX-2) inhibitors).
- Serious or non-healing wound, ulcer or bone fracture.
- Proteinuria at screening as demonstrated by either:
- Urine protein:creatinine (UPC) ratio greater than or equal to 1.0 at screening OR
- Urine dipstick for proteinuria greater than or equal to 2+ (patients discovered to have greater than or equal to 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate less than or equal to 1g of protein in 24 hours to be eligible).
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months
- Invasive procedures defined as follows:
- Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
- +30 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Related Publications (6)
Bigner SH, Bjerkvig R, Laerum OD. DNA content and chromosomal composition of malignant human gliomas. Neurol Clin. 1985 Nov;3(4):769-84.
PMID: 3001489BACKGROUNDMoss AR. Occupational exposure and brain tumors. J Toxicol Environ Health. 1985;16(5):703-11. doi: 10.1080/15287398509530780.
PMID: 4093991BACKGROUNDBovet P, Lob M. [Cancer mortality among the workers of a Swiss rubber goods factory. Epidemiological study, 1955-75]. Schweiz Med Wochenschr. 1980 Aug 30;110(35):1277-87. French.
PMID: 6999620BACKGROUNDOdia Y, Sul J, Shih JH, Kreisl TN, Butman JA, Iwamoto FM, Fine HA. A Phase II trial of tandutinib (MLN 518) in combination with bevacizumab for patients with recurrent glioblastoma. CNS Oncol. 2016;5(2):59-67. doi: 10.2217/cns-2015-0010. Epub 2016 Feb 10.
PMID: 26860632DERIVEDOdia Y, Shih JH, Kreisl TN, Fine HA. Bevacizumab-related toxicities in the National Cancer Institute malignant glioma trial cohort. J Neurooncol. 2014 Nov;120(2):431-40. doi: 10.1007/s11060-014-1571-6. Epub 2014 Aug 7.
PMID: 25098701DERIVEDLehky TJ, Iwamoto FM, Kreisl TN, Floeter MK, Fine HA. Neuromuscular junction toxicity with tandutinib induces a myasthenic-like syndrome. Neurology. 2011 Jan 18;76(3):236-41. doi: 10.1212/WNL.0b013e3182074a69.
PMID: 21242491DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Katherine Warren
- Organization
- National Cancer Institute, National Institutes of Health
Study Officials
- PRINCIPAL INVESTIGATOR
Howard Fine, M.D.
National Cancer Institute, National Institutes of Health
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
April 25, 2008
First Posted
April 28, 2008
Study Start
April 1, 2008
Primary Completion
July 1, 2011
Study Completion
July 1, 2011
Last Updated
November 5, 2015
Results First Posted
August 31, 2012
Record last verified: 2015-10