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

Mass General Brigham

Status and phase

Completed

Phase 1

Conditions

Glioblastoma

Treatments

Drug: PTK787/ZK 222584

Procedure: Radiation Therapy

Drug: Temozolomide

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00385853

06-013

Details and patient eligibility

About

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.

Full 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.

Enrollment

19 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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 aprepitant, dolasetron, and tropisetron as antiemetics are excluded