PTK787/ZK 222584 in Combination With Temozolomide and Radiation in Patients With Glioblastoma Taking Enzyme-Inducing Anti-Epileptic Drugs - Full Text View

Sponsors and Collaborators:	Massachusetts General Hospital Dana-Farber Cancer Institute Novartis
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00385853

Purpose

PTK is an investigational new drug that has been shown in early laboratory studies to prevent the formation of new blood vessels that allow the tumor to grow. These studies have shown that the study drug can potentially improve the effectiveness of additional radiation and chemotherapy. With this study, we would like to examine the effects of PTK when used in combination with radiation therapy and the anti-cancer drug temozolomide, the standard treatment for patients with newly diagnosed glioblastoma. We would also like to learn how the study drug is absorbed, distributed, and cleared from the body.

Condition	Intervention	Phase
Glioblastoma	Drug: PTK787/ZK 222584 Drug: Temozolomide Procedure: Radiation Therapy	Phase I

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

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide Vatalanib Butanedioic acid, compd. with N-(4-chlorophenyl)-4-(4-pyridinylmethyl)-1-phthalazinamine (1:1)

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety Study
Official Title:	A Phase I Study of PRK787/ZK 222584 in Combination With Daily Temozolomide and Radiation in Patients With Newly Diagnosed Glioblastoma

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

To determine the maximal tolerated dose, safety and feasibility of PTK787/ZK 222584 in combination with temozolomide and radiation in patients with newly diagnosed glioblastoma. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Determine the pharmacologic profile of PTK787/ZK 222584 in this patient population [ Time Frame: 2 years ] [ Designated as safety issue: No ]
determine the overall survival of patients with recurrent GM treated with PTK787/ZK 222584, when combined with temozolomide and radiation therapy. [ Time Frame: TBD ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	September 2006
Estimated Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Intervention Details:

Twice daily for each 28-day cycle

Daily for each 28-day cycle

For 7 weeks beginning on day 5 of the first treatment cycle

Detailed Description:

Since we are looking for the highest dose of PTK that can be administered safely without severe or unmanageable side effects, not everyone who participates will get the same dose of PTK. A small group will be enrolled onto the study and given a certain dose. If they tolerate it well, the next small group enrolled will receive a higher dose. This will continue until the highest dose that can be given without severe or unmanageable side effects is found.
Participants will receive PTK twice daily along with temozolomide daily during each treatment cycle. Each treatment cycle lasts 28 days.
PTK will start on Day 0 of the first cycle and will be given twice daily for the 7 weeks the participant receives radiation therapy.
Daily doses of temozolomide will begin on Day of the first cycle and continue until the last dose of radiation therapy in cycle 1.
Each participant will receive 7 weeks of radiation therapy. Radiation therapy will start on Day 5 of the first cycle and will be administered monday through friday, except on holidays.
When radiation stops, temozolomide and PTK will be given for a maximum of 6 post-radiation cycles of study treatment. During these cycles, PTK and temozolomide will be given for 5 consecutive days followed by 23 days of no drugs.
Tests will be performed routinely throughout the study treatment and include; chest x-rays, blood tests, physical exams, urine tests and ECG.
The following procedures will be performed at the end of the study or after the participants last dose of study medication; tumor assessment by MRI, routine blood draws, neurological/physical exam and, medical history review.

Eligibility

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

Criteria

Inclusion Criteria:

All patients must have histologically verified glioblastoma. Patients mus have paraffin blocks of tumor that must be sent for analysis.
18 years of age or older
Karnofsky Performance Status greater than or equal to 60
Adequate laboratory values as described by the protocol
Life expectancy of greater than 12 weeks
Patient must be able to undergo serial MR imaging
Patients must be on an enzyme-inducing anti-epileptic drug(s) as listed in the protocol
No steroids or a stable dose of steroids for at least 5 days or a decreasing dose
Mini-mental status examination of 15 or greater

Exclusion Criteria:

Pregnant or breast-feeding women
Concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast
Prior chemotherapy or cranial radiation therapy for glioblastoma
Prior biologic or immunotherapy less than 2 weeks prior to registration
If the patient surgery is more than 16 days or less than 13 days from the start of PTK787/ZK 222854
Prior therapy with anti-VEGF agents
Pleural effusion or ascites that causes respiratory compromise
Concurrent severe and/or uncontrolled medical conditions which could compromise participation is the study
Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of PTK787/ZK 222584
Confirmed diagnosis of human immunodeficiency virus (IV)
Patients who are taking therapeutic warfarin sodium or other anticoagulants or anti-platelet agents
Patients requiring aprepritan, dolasetron, and tropisetron as antiemetics are excluded

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00385853

Contacts

Contact: Tracy Batchelor, MD

617-643-1938

tbatchelor@partners.org

Locations

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

Sponsors and Collaborators

Massachusetts General Hospital

Dana-Farber Cancer Institute

Novartis

Investigators

Principal Investigator:

Tracy Batchelor, MD

Massachusetts General Hospital

More Information

Responsible Party:	Massachusetts General Hospital ( Tracy Batchelor, MD )
Study ID Numbers:	06-013
Study First Received:	October 6, 2006
Last Updated:	December 21, 2007
ClinicalTrials.gov Identifier:	NCT00385853
Health Authority:	United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:

PTK
temozolomide
glioblastoma

Study placed in the following topic categories:

Neuroectodermal Tumors
Glioblastoma
Astrocytoma
Epilepsy
Neoplasms, Germ Cell and Embryonal

Neuroepithelioma
Glioma
Temozolomide
Vatalanib
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Neoplasms, Nerve Tissue

Enzyme Inhibitors
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Protein Kinase Inhibitors
Alkylating Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009