Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Zactima With Temodar During Radiation Treatment for Newly Diagnosed Stage IV Brain Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
University of Virginia
Memorial Sloan Kettering Cancer Center.
Henry Ford Hospital
Information provided by (Responsible Party):
Patrick Y. Wen, MD, Dana-Farber/Brigham and Women's Cancer Center
ClinicalTrials.gov Identifier:
NCT00441142
First received: February 27, 2007
Last updated: February 27, 2015
Last verified: February 2015
Results First Received: February 5, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Glioblastoma Multiforme
Gliosarcoma
Interventions: Drug: ZD6474
Drug: temozolomide
Radiation: Radiation Therapy

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Although 119 pts were registered & enrolled to trial, only 111 began study tx (8 enrolled pts did not receive tx on study). 7 pts randomized to Ph II Arm A removed their consent before starting study tx, and 1 Ph II Arm B pt was removed from study before starting tx, as pt clinically declined immediately following registration/randomization.

Reporting Groups
  Description
Phase I: Dose Level -1: RT + TMZ + Vandetanib @ 200 mg/Day

ZD6474 (Vandetanib) daily (to begin 5-7 days prior to starting participant's RT) Temozolomide (75 mg/m2 daily for 6 weeks) with concurrent fractionated radiation therapy for approximately 6 weeks (XRT must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy), followed by 4-6 weeks rest.

Followed by:

12 cycles of adjuvant temozolomide [at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle; if 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given].

ZD6474 (Vandetanib) daily for the twelve (12) 28-day cycles of adjuvant temozolomide, with the option to continue until participant experiences an unacceptable toxicity or his/her tumor progresses.

Phase I: Dose Level -2: RT + TMZ + Vandetanib @ 100 mg/Day

ZD6474 (Vandetanib) daily (to begin 5-7 days prior to starting participant's RT) Temozolomide (75 mg/m2 daily for 6 weeks) with concurrent fractionated radiation therapy for approximately 6 weeks (XRT must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy), followed by 4-6 weeks rest.

Followed by:

12 cycles of adjuvant temozolomide [at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle; if 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given].

ZD6474 (Vandetanib) daily for the twelve (12) 28-day cycles of adjuvant temozolomide, with the option to continue until participant experiences an unacceptable toxicity or his/her tumor progresses.

Phase II: Arm A (Control Group: RT + TMZ)

The "Induction" Phase:

Temozolomide (75 mg/m2 daily for 6 weeks) with concurrent fractionated radiation therapy for approximately 6 weeks (XRT must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy), followed by 4-6 weeks rest.

Followed by the "Maintenance" Phase:

12 cycles of adjuvant temozolomide [at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle; if 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given].

Phase II: Arm B (Experimental Group: RT + TMZ + Vandetanib)

The "Induction" Phase:

ZD6474 (Vandetanib) daily (to begin 5-7 days prior to starting participant’s RT) Temozolomide (75 mg/m2 daily for 6 weeks) with concurrent fractionated radiation therapy for approximately 6 weeks (XRT must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy), followed by 4-6 weeks rest.

Followed by the "Maintenance" Phase:

12 cycles of adjuvant temozolomide [at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle; if 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given].

ZD6474 (Vandetanib) daily for the twelve (12) 28-day cycles of adjuvant temozolomide, with the option to continue until participant experiences an unacceptable toxicity or his/her tumor progresses.


Participant Flow:   Overall Study
    Phase I: Dose Level -1: RT + TMZ + Vandetanib @ 200 mg/Day     Phase I: Dose Level -2: RT + TMZ + Vandetanib @ 100 mg/Day     Phase II: Arm A (Control Group: RT + TMZ)     Phase II: Arm B (Experimental Group: RT + TMZ + Vandetanib)  
STARTED     6     7     29     69  
COMPLETED     0     0     7     1  
NOT COMPLETED     6     7     22     68  
Adverse Event                 2                 3                 3                 22  
Lack of Efficacy                 3                 3                 17                 32  
Withdrawal by Subject                 0                 0                 2                 10  
Patient still receiving active study tx                 1                 0                 0                 2  
Physician Decision                 0                 1                 0                 1  
Death                 0                 0                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Phase I: Dose Level -1: RT + TMZ + Vandetanib @ 200 mg/Day

ZD6474 (Vandetanib) daily (to begin 5-7 days prior to starting participant's RT) Temozolomide (75 mg/m2 daily for 6 weeks) with concurrent fractionated radiation therapy for approximately 6 weeks (XRT must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy), followed by 4-6 weeks rest.

Followed by:

12 cycles of adjuvant temozolomide [at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle; if 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given].

ZD6474 (Vandetanib) daily for the twelve (12) 28-day cycles of adjuvant temozolomide, with the option to continue until participant experiences an unacceptable toxicity or his/her tumor progresses.

Phase I: Dose Level -2: RT + TMZ + Vandetanib @ 100 mg/Day

ZD6474 (Vandetanib) daily (to begin 5-7 days prior to starting participant's RT) Temozolomide (75 mg/m2 daily for 6 weeks) with concurrent fractionated radiation therapy for approximately 6 weeks (XRT must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy), followed by 4-6 weeks rest.

Followed by:

12 cycles of adjuvant temozolomide [at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle; if 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given].

ZD6474 (Vandetanib) daily for the twelve (12) 28-day cycles of adjuvant temozolomide, with the option to continue until participant experiences an unacceptable toxicity or his/her tumor progresses.

Phase II: Arm A (Control Group: RT + TMZ)

The "Induction" Phase:

Temozolomide (75 mg/m2 daily for 6 weeks) with concurrent fractionated radiation therapy for approximately 6 weeks (XRT must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy), followed by 4-6 weeks rest.

Followed by the "Maintenance" Phase:

12 cycles of adjuvant temozolomide [at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle; if 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given].

Phase II: Arm B (Experimental Group: RT + TMZ + Vandetanib)

The "Induction" Phase:

ZD6474 (Vandetanib) daily (to begin 5-7 days prior to starting participant’s RT) Temozolomide (75 mg/m2 daily for 6 weeks) with concurrent fractionated radiation therapy for approximately 6 weeks (XRT must be given by external beam to a partial brain field in daily fractions of 180-200 cGy, to a planned total dose to the tumor of approximately 6000 cGy), followed by 4-6 weeks rest.

Followed by the "Maintenance" Phase:

12 cycles of adjuvant temozolomide [at 150 mg/m2/day orally for 5 days (days 1-5) of a 28-day TMZ cycle; if 150 mg/m2/day is tolerated without difficulty and the investigator feels the patient can tolerate 200 mg/m2/day, then an increase to a maximum of 200 mg/m2/day for five days every 28 days may be given].

ZD6474 (Vandetanib) daily for the twelve (12) 28-day cycles of adjuvant temozolomide, with the option to continue until participant experiences an unacceptable toxicity or his/her tumor progresses.

Total Total of all reporting groups

Baseline Measures
    Phase I: Dose Level -1: RT + TMZ + Vandetanib @ 200 mg/Day     Phase I: Dose Level -2: RT + TMZ + Vandetanib @ 100 mg/Day     Phase II: Arm A (Control Group: RT + TMZ)     Phase II: Arm B (Experimental Group: RT + TMZ + Vandetanib)     Total  
Number of Participants  
[units: participants]
  6     7     29     69     111  
Age  
[units: participants]
         
<=18 years     0     0     0     0     0  
Between 18 and 65 years     6     5     24     50     85  
>=65 years     0     2     5     19     26  
Gender  
[units: participants]
         
Female     1     2     13     25     41  
Male     5     5     16     44     70  
Race (NIH/OMB)  
[units: participants]
         
American Indian or Alaska Native     0     0     0     0     0  
Asian     0     0     2     1     3  
Native Hawaiian or Other Pacific Islander     0     0     0     0     0  
Black or African American     0     0     1     2     3  
White     6     7     25     63     101  
More than one race     0     0     0     0     0  
Unknown or Not Reported     0     0     1     3     4  
Baseline (Day 1) Karnofsky Performance Score (KPS) [1]
[units: Participants]
         
100     0     5     7     15     27  
90     2     2     15     30     49  
80     1     0     2     17     20  
70     3     0     3     5     11  
60     0     0     2     2     4  
[1] 100 Normal; no complaints/evidence of dz 90 Able to carry on normal activity; minor signs/symptoms of dz 80 Normal activity w/ effort; some sign/symptoms of dz 70 Cares for self; unable to carry on normal activity or do active work 60 Requires occasional assistance, but able to care for most personal needs 50 Requires considerable assistance & frequent medical care 40 Disabled; requires special care & assistance 30 Severely disabled; hosp indicated, although death not imminent 20 Very sick; hosp & active support tx necessary 10 Moribund; fatal processes progressing rapidly 0 Dead



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants That Experienced a Dose-limiting Toxicity (DLT)   [ Time Frame: 2 years ]

2.  Primary:   Median Overall Survival (OS) of Phase II Patients   [ Time Frame: 3 years ]

3.  Secondary:   Median Progression-free Survival (PFS), as Calculated by the # of Months Patients Remain Progression-free   [ Time Frame: 3 years ]

4.  Secondary:   PHASE II: To Further Evaluate the Safety Profile of ZD6474 (Vandetanib) in Combination With Radiation Therapy and Temozolomide in This Patient Population.   [ Time Frame: 3 years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   Yes

5.  Secondary:   PHASE I: To Define the Safety of ZD6474 (Vandetanib) With Radiation Therapy and Concomitant and Adjuvant Temozolomide in This Population.   [ Time Frame: 2 years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   Yes


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Eudocia Quant Lee
Organization: Dana-Farber Cancer Institute
phone: 617-632-2166
e-mail: eqlee@partners.org


No publications provided


Responsible Party: Patrick Y. Wen, MD, Dana-Farber/Brigham and Women's Cancer Center
ClinicalTrials.gov Identifier: NCT00441142     History of Changes
Other Study ID Numbers: 06-377, IRUSZACT0018
Study First Received: February 27, 2007
Results First Received: February 5, 2015
Last Updated: February 27, 2015
Health Authority: United States: Food and Drug Administration