Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
Phase I:
The purpose of this research study is to determine the safety of the combination treatment of ZD6474 (Vandetanib) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (Temodar) and radiation therapy. This agent is investigational for the treatment of glioblastomas. We will determine the highest dose of ZD6474 (Vandetanib) that can be given safely when combined with temozolomide (Temodar) and radiation therapy.
Phase II:
The purpose of this research study is to determine the efficacy of the combination treatment of ZD6474 (Vandetanib) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (Temodar) and radiation therapy. This agent is investigational for the treatment of glioblastomas.
All subjects participating in this research study must NOT be taking a certain type of anti-seizure medication called enzyme inducing anticonvulsant drugs. These drugs include (but are not limited to) the following medications: Dilantin, Tegretol, Phenobarbital and trileptal.
Full description
Currently the standard treatment for glioblastomas and gliosarcomas is temozolomide (Temodar) and radiation therapy. This study is being done because research has shown that glioblastomas have genetic changes that may cause an excess of certain cell growth factors and their receptors, which can cause uncontrolled tumor growth. The drug being used in this research study, ZD6474 (Vandetanib), is designed to block the receptors to two of these growth factors, the vascular endothelial growth factor (VEGF) and the epidermal growth factor (EGF). These growth factors are important in pathways that promote tumor growth and increasing blood supply to the tumor. Blocking these receptors may reduce the blood supply to the tumor and help slow down tumor growth. There is also laboratory evidence that blocking these receptors may increase the sensitivity of glioblastomas to radiation therapy.
This research study is a Phase I/II clinical trial.
Phase I clinical trials test the safety of an investigational drug. Phase I studies also try to define the appropriate dose of the investigational drug to use for further studies. We will determine the highest dose of ZD6474 (Vandetanib) that can be given safely when combined with temozolomide (Temodar) and radiation therapy.
The purpose of Phase II of this research study is to determine the efficacy of the combination treatment of ZD6474 (Vandetanib) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (Temodar) and radiation therapy. It will look to see how patients fare on treatment (if they progress and when, how they are doing after 12 months of treatment). In this research study, the safety of the combination treatment of ZD6474 (Vandetanib) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (Temodar) and radiation therapy will be further evaluated. We will also be looking at samples to see if there are correlations between them and how well patients do on treatment.
This agent is investigational for the treatment of glioblastomas. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it. It also means that the FDA (U.S. Food and Drug Administration) has not approved ZD6474 (Vandetanib) for use for your type of cancer. All subjects participating in this research study must NOT be taking a certain type of anti-seizure medication called enzyme inducing anticonvulsant drugs. These drugs include the following medications: Dilantin, Tegretol, Phenobarbital and trileptal.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
All inclusion and exclusion criteria apply to both phase I and II patients.
Inclusion Criteria:
Subjects with histologically proven intracranial glioblastoma multiforme (GBM) and gliosarcoma will be eligible for this protocol.
Gadolinium MRI or contrast CT must be obtained within 14 days prior to registration.
Patients must have a plan to begin treatment with ZD6474 (vandetanib) and/or temozolomide 21 to 35 days after surgical resection or 14 to 35 days after stereotactic biopsy.
Subjects must have a plan to begin partial brain radiotherapy 5-7 days after beginning ZD6474. Radiotherapy must be a) at the Radiation Oncology Department of the participating institution, b) at an affiliated site that is currently approved to participate in any trial of the Radiation Therapy Oncology Group (RTOG), or c) at another location with prior approval from the Overall PI of the trial. Radiotherapy must be given by external beam to a partial brain field in daily fractions of 180 to 200 cGy, to a planned total dose to the tumor of approximately 6000 cGy. Stereotactic radiosurgery and brachytherapy will not be allowed.
If it is deemed in the best interest of the patient, intensity modulated radiation therapy (IMRT) is allowable on this trial. If IMRT is administered, dose specifics must be conducted per institutional guidelines.
Subjects must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while being treated with ZD6474 (ZactimaTM), with the exception of temozolomide.
All subjects must sign an informed consent indicating that they are aware of the investigational nature of this study prior to any study-related procedures. Patients must be registered with in the Dana Farber Cancer Institute's Quality Assurance Office for Clinical Trials prior to treatment with ZD6474 (Vandetanib). Patients must sign an authorization for the release of their protected health information.
Subjects can be male or female, and must be >/= 18 years old, with a life expectancy > 12 weeks.
Subjects must be able to care for themselves (KPS>/=60).
Subjects must have adequate labs as defined below:
Women of childbearing potential must have a negative pregnancy test documented within 14 days prior to registration.
Men and women of childbearing potential must agree to use adequate contraception while receiving study medication and continue for at least two months (five half-lives) after their last dose of study medication.
Patients must have sufficient tissue available from their prior biopsy/surgery: at least 10 (preferably 20) unstained slides or 1 tissue block.
Patients must agree not to donate blood during the trial and for 3 months following their last dose of trial treatment
Exclusion Criteria:
Subjects must not have had prior cranial radiation therapy.
Subjects must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors.
Subjects must not have received prior Gliadel wafers.
Subjects must not have received any investigational agents within 30 days prior to commencing study treatment
Subjects must not have evidence of severe or uncontrolled systemic disease or any concurrent condition that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
Subjects with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
Subjects must not have any unresolved toxicity greater than CTC grade 1 related to previous anti-cancer therapy.
Subjects must not have active infection.
Subjects must not be pregnant/breast feeding.
Subjects must not have any disease that will obscure toxicity or dangerously alter drug metabolism.
Subjects must not have history of any clinically significant cardiac event, or evidence of heart disease.
Subjects must not be taking any enzyme-inducing anti-epileptic drugs (EIAED) or other drugs that are potent inducers of CYP3A4 function (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbitol and St. John's Wort). If patients were previously on EIAEDs and these have been discontinued, patients must have been off the agent for at least 7 days prior to registration.
Subjects must not be taking concomitant medications known to prolong the QT interval and have a risk of inducing Torsade de Pointes (TdP). Any concurrent medication with a known risk of inducing TdP that, in the investigator's opinion cannot be discontinued, will be allowed; however, these patients must be monitored closely.
Subjects must not have uncontrolled hypertension (high blood pressure).
Subjects must not have active diarrhea that may affect the ability of the patient to absorb or tolerate ZD6474 (Vandetanib).
Subjects with confirmed diagnosis of human immunodeficiency virus (HIV) infection are excluded at the investigator's discretion if he/she feels that 1) a potential drug interaction between ZD6474 (Vandetanib) and any of the patient's anti-HIV medications could influence the efficacy of the anti-HIV medication, or 2) it may place the patient at risk due to the pharmacologic activity of ZD6474 (Vandetanib).
Subjects' pre-operative MRI must not demonstrate significant intratumoral or peritumoral hemorrhage & post-operative MRI must not demonstrate a large amount of peri-operative parenchymal hemorrhage. (Patients may have postoperative intracavitary blood.)
Subjects must not have had major surgery (unrelated to the glioblastoma) within 4 weeks before starting study therapy, and subjects cannot have a surgical incision that has not completely healed before starting study therapy.
Subjects must not be receiving Coumadin (subjects may take low molecular weight heparin).
Subjects must not have enrolled on this trial previously.
Subjects must have had no involvement in the planning or conduct of the study (applies to both AstraZeneca staff or staff at the study site).
Any of the following lab results will result in patient exclusion from trial:
NOTE: In cases where the serum calcium is below the normal range, 2 options would be available:
Primary purpose
Allocation
Interventional model
Masking
119 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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