NCT00441142

Zactima With Temodar During Radiation Treatment for Newly Diagnosed Stage IV Brain Tumors

Phase I/II Study of ZD6474 (Vandetanib) With Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 119 (actual)
• Sponsor: Patrick Y. Wen, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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.

Conditions

• Glioblastoma Multiforme
• Gliosarcoma

Interventions

Type	Name	Description
DRUG	ZD6474	Taken orally once a day (at 100 mg/day is the phase II dose; the MTD determined by the phase I portion of the trial) until disease gets worse or participants experience unacceptable side effects
DRUG	temozolomide	During the 'Induction' phase: 75/mg/m2/day temozolomide will be given orally daily for 6 weeks (42 days) during radiation therapy, beginning either the night before or on the first day of the first fraction of radiation, including weekends and holidays. This is followed by a 4-6 week break. During the 'Maintenance' phase: The first post-radiation temozolomide cycle will be administered at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle. If 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given. This is given for 12 cycles.
RADIATION	Radiation Therapy	Radiotherapy must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy.

Timeline

• Start date: 2007-05-25
• Primary completion: 2013-08-31
• Completion: 2017-10-10
• First posted: 2007-02-28
• Last updated: 2019-03-05
• Results posted: 2015-03-02

Locations

7 sites across 1 country: United States