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

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00385853

Collaborator

Dana-Farber Cancer Institute (Other), Novartis (Industry)

Enrollment

Locations

Arm

Duration (Months)

9.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Glioblastoma	Drug: PTK787/ZK 222584 Drug: Temozolomide Procedure: Radiation Therapy	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of PRK787/ZK 222584 in Combination With Daily Temozolomide and Radiation in Patients With Newly Diagnosed Glioblastoma

Study Start Date :

Sep 1, 2006

Actual Primary Completion Date :

Sep 1, 2011

Actual Study Completion Date :

Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PTK787 Single arm study of PTK787	Drug: PTK787/ZK 222584 Twice daily for each 28-day cycle Drug: Temozolomide Daily for each 28-day cycle Procedure: Radiation Therapy For 7 weeks beginning on day 5 of the first treatment cycle

Arm

Intervention/Treatment

Experimental: PTK787

Single arm study of PTK787

Drug: PTK787/ZK 222584

Twice daily for each 28-day cycle

Drug: Temozolomide

Daily for each 28-day cycle

Procedure: Radiation Therapy

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

Outcome Measures

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. [2 years]

Secondary Outcome Measures

Determine the pharmacologic profile of PTK787/ZK 222584 in this patient population [2 years]
determine the overall survival of patients with recurrent GM treated with PTK787/ZK 222584, when combined with temozolomide and radiation therapy. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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