Official Title: “Phase I/II Study of ZD6474 (ZactimaTM) With Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma”

Phase I:

The purpose of this research study is to determine the safety of the combination treatment of ZD6474 (ZactimaTM) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (TemodarÒ) and radiation therapy. This agent is investigational for the treatment of glioblastomas. We will determine the highest dose of ZD6474 (ZactimaTM) that can be given safely when combined with temozolomide (TemodarÒ) and radiation therapy. 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.

Phase II:

The purpose of this research study is to determine the safety and effectiveness of the combination treatment of ZD6474 (ZactimaTM) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (TemodarÒ) 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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: May 2010

Currently the standard treatment for glioblastomas and gliosarcomas is temozolomide (TemodarÒ) 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 (ZactimaTM), 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. "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 (ZactimaTM) for use for your type of cancer.

The purpose of Phase II of this research study is to determine the safety of the combination treatment of ZD6474 (ZactimaTM) with the standard therapy for glioblastomas and gliosarcomas, temozolomide (TemodarÒ) and radiation therapy. This agent is investigational for the treatment of glioblastomas. We will determine the highest dose of ZD6474 (ZactimaTM) that can be given safely when combined with temozolomide (TemodarÒ) and radiation therapy. 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.

Intervention(s) in this Clinical Trial

• Drug: ZD6474
  • Taken orally once a day until disease gets worse or participants experience unacceptable side effects

Primary Measures

• PHASE I: To determine the maximum tolerated dose of ZD6474 (Zactima)
  • Time Frame: 2 years
    Safety Issue?: Yes
• PHASE II: To determine the efficacy of ZD6474 (Zactima) in combination with radiation
  • Time Frame: 3 years
    Safety Issue?: No

Secondary Measures

• PHASE II: To determine the 15-month survival and median time to tumor progression.
  • Time Frame: 3 years
    Safety Issue?: No
• To further evaluate the safety profile of ZD6474 (Zactima) in combination with radiation therapy
  • Time Frame: 3 years
    Safety Issue?: Yes

Inclusion Criteria:

• Subjects with histologically proven intracranial glioblastoma multiforme (GBM) and gliosarcoma will be eligible for this protocol.
• Diagnosis will have been established by biopsy or resection no more than 4 weeks prior to registration.
• Gadolinium MRI or contrast CT must be obtained within 14 days prior to registration.
• Subjects must have a plan to begin partial brain radiotherapy 5-7 days after beginning
• ZD6474 (ZactimaTM). Radiotherapy must be a) at the Radiation Oncology Department of the participating institution, or b) at an affiliated site that is currently approved to participate in any trial of the Radiation Therapy Oncology Group (RTOG).
• 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.
• Subjects must be > 18 years old.
• Subjects must be able to care for themselves.
• 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.

Exclusion Criteria:

• Subjects must not have had prior cranial radiation therapy.
• Subjects must not have had prior treatment for brain tumors.
• Subjects must not have received prior Gliadel wafers.
• Subjects must not have any significant medical illnesses.
• 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 active infection.
• Subjects must not be pregnant/breast feeding.
• Subjects must not have history of any clinically significant cardiac event, or evidence of heart disease.
• Subjects must not have any enzyme-inducing anti-epileptic drugs (Dilantin, Tegretol, valproic acid, trileptal.
• Subjects must not have uncontrolled high blood pressure.
• Subjects must not have active diarrhea that may affect the ability of the patient to absorb or tolerate ZD6474 (ZactimaTM).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Dana-Farber Cancer Institute

Overall Clinical Trial Officials and Contacts

Patrick Y Wen, MD Principal Investigator Dana-Farber Cancer Institute  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00441142

Study ID Number: 06-377

ClinicalTrials.gov Identifier: NCT00441142

Health Authority: United States: Food and Drug Administration