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

Primary Purpose

Glioblastoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PTK787/ZK 222584
Temozolomide
Radiation Therapy
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring PTK, temozolomide, glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Dana-Farber Cancer Institute
  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PTK787

Arm Description

Single arm study of PTK787

Outcomes

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.

Secondary Outcome Measures

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

Full Information

First Posted
October 6, 2006
Last Updated
October 18, 2013
Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute, Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00385853
Brief Title
PTK787/ZK 222584 in Combination With Temozolomide and Radiation in Patients With Glioblastoma Taking Enzyme-Inducing Anti-Epileptic Drugs
Official Title
A Phase I Study of PRK787/ZK 222584 in Combination With Daily Temozolomide and Radiation in Patients With Newly Diagnosed Glioblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute, Novartis

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma
Keywords
PTK, temozolomide, glioblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PTK787
Arm Type
Experimental
Arm Description
Single arm study of PTK787
Intervention Type
Drug
Intervention Name(s)
PTK787/ZK 222584
Intervention Description
Twice daily for each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Intervention Description
Daily for each 28-day cycle
Intervention Type
Procedure
Intervention Name(s)
Radiation Therapy
Intervention Description
For 7 weeks beginning on day 5 of the first treatment cycle
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Determine the pharmacologic profile of PTK787/ZK 222584 in this patient population
Time Frame
2 years
Title
determine the overall survival of patients with recurrent GM treated with PTK787/ZK 222584, when combined with temozolomide and radiation therapy.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 aprepitant, dolasetron, and tropisetron as antiemetics are excluded
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tracy Batchelor, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20821342
Citation
Gerstner ER, Eichler AF, Plotkin SR, Drappatz J, Doyle CL, Xu L, Duda DG, Wen PY, Jain RK, Batchelor TT. Phase I trial with biomarker studies of vatalanib (PTK787) in patients with newly diagnosed glioblastoma treated with enzyme inducing anti-epileptic drugs and standard radiation and temozolomide. J Neurooncol. 2011 Jun;103(2):325-32. doi: 10.1007/s11060-010-0390-7. Epub 2010 Sep 7.
Results Reference
result

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

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