Sunitinib Tumor Levels in Patients Not on Enzyme-Inducing Anti-Epileptic Drugs Undergoing Debulking Surgery for Recurrent Glioblastoma - Full Text View

Purpose

The purpose of this research study is to determine if sunitinib can get past the blood-brain barrier and into the brain tumor. Sunitinib has shown promising results in treating other cancers and works by blocking blood flow to tumors, which may prevent them from growing further. At the present time, there is no chemotherapy that can cure glioblastoma. The reason why chemotherapy is not fully effective is that many drugs cannot penetrate into brain tumors. This is due to the presence of the blood-brain barrier (BBB) which normally protects the brain from substances in the blood.

Condition	Intervention
Glioblastoma Brain Tumor	Drug: Sunitinib

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Pilot Study of Sunitinib Tumor Levels in Patients Not on Enzyme-Inducing Anti-Epileptic Drugs Undergoing Debulking Surgery for Recurrent Glioblastoma

Resource links provided by NLM:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Brain Cancer Cancer Epilepsy

Drug Information available for: Sunitinib malate Sunitinib

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

To assess the ability of sunitinib to achieve a target tumor: plasma ration greater than or equal to 0.2 in patients with recurrent GM. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine if there is an association between growth factor receptor inhibition and tumor phenotype, tumor: plasma ratio of sunitinib and overall survival. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	12
Study Start Date:	May 2007
Estimated Study Completion Date:	May 2012
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Intervention Details:

Taken orally on days 1-7 prior to surgery and then starting again on Day 22 for 4 weeks followed by a 2 week rest period

Detailed Description:

Participants will take the study drug, sunitinib, for 7 days prior to their surgery. The surgery is part of the routine care for glioblastoma and will be performed on Day 8. The study drug is supplied in capsule form and is to be taken at home.
On Day 7 participants will come to the clinic and have the following tests and procedures performed: Neurological and physical examination; vital signs; and blood samples. On day 9 (the day after the surgery) an MRI scan will be performed.
Fourteen days after the participants surgery (Day 22), they will restart sunitinib treatment. They will take the study drug once a day for 4 weeks followed by a 2 week rest period (no study drug treatment). This 6 week period is called a cycle of study treatment. Participants can continue to receive cycles of study treatment as long as their disease does not progress and they do not experience any serious side-effects.
Before each new cycle of study treatment (once every 6 weeks) the participant will come into the clinic for the following tests: Neurological and physical examination; vital signs; blood sample; urine sample; MRI scan of the brain (done every even cycle).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically confirmed glioblastoma
18 years of age or older
Karnofsky Performance Status 60 or greater
Patient must be on no anti-epileptic drugs (AED) or AED that are non-enzyme inducing (NEIAED)
There is no limit to the number of prior chemotherapy regimens
No concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast. Patients with prior malignancies must be disease-free for 5 years or more
Mini-mental status examination score of 15 or less
Resolution of all acute toxic effect of prior chemotherapy, radiotherapy, or surgical procedures to grade 1 or less
Adequate organ function as outlined in the protocol

Exclusion Criteria:

Major surgery within 4 weeks of starting the study treatment
Radiation therapy within 3 months of starting the study treatment
Chemotherapy within 4 weeks (within 6 weeks for nitrosoureas) prior to entering the study
Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials are allowed
Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure. stroke or transient ischemic attack, or pulmonary embolism
Ongoing cardiac dysrhythmias of NCI CTCAE grade 2 or greater
Prolonged QTc interval on baseline EKG
Hypertension that cannot be controlled by medications
Patients must not have a known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhages in the past
Patients must be on therapeutic doses of anti-coagulants or anti-platelet agents while taking sunitinib
Grade 3 systemic hemorrhage within 4 weeks fo starting the study treatment
Patients whose MRI scan shows clinically significant intratumoral or peritumoral hemorrhage
Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or active infection
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
Concomitant use of ketoconazole and other agents known to induce CYP3A4
Pregnancy or breastfeeding
History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00864864

Locations

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Massachusetts General Hospital

Brigham and Women's Hospital

Dana-Farber Cancer Institute

Pfizer

Investigators

Principal Investigator:

Scott Plotkin, MD, PhD

Massachusetts General Hospital

More Information

No publications provided

Responsible Party:	Scott Randall Plotkin, MD, PhD, Associate Professor of Neurology, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00864864 History of Changes
Other Study ID Numbers:	06-307
Study First Received:	March 17, 2009
Last Updated:	September 2, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:

sunitinib

Additional relevant MeSH terms:

Brain Neoplasms
Glioblastoma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Anticonvulsants
Sunitinib
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on May 16, 2013