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

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ClinicalTrials.gov Identifier: NCT00441142
Recruitment Status : Completed
First Posted : February 28, 2007
Results First Posted : March 2, 2015
Last Update Posted : March 5, 2019
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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Glioblastoma Multiforme
Gliosarcoma
Interventions Drug: ZD6474
Drug: temozolomide
Radiation: Radiation Therapy
Enrollment 119
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title 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)
Hide Arm/Group Description

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.

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.

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].

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.

Period Title: Overall Study
Started 6 7 29 69
Completed 0 0 7 1
Not Completed 6 7 22 68
Reason Not Completed
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
Arm/Group Title 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
Hide Arm/Group Description

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.

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.

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].

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 of all reporting groups
Overall Number of Baseline Participants 6 7 29 69 111
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 7 participants 29 participants 69 participants 111 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
 100.0%
5
  71.4%
24
  82.8%
50
  72.5%
85
  76.6%
>=65 years
0
   0.0%
2
  28.6%
5
  17.2%
19
  27.5%
26
  23.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 7 participants 29 participants 69 participants 111 participants
Female
1
  16.7%
2
  28.6%
13
  44.8%
25
  36.2%
41
  36.9%
Male
5
  83.3%
5
  71.4%
16
  55.2%
44
  63.8%
70
  63.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 7 participants 29 participants 69 participants 111 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
2
   6.9%
1
   1.4%
3
   2.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
1
   3.4%
2
   2.9%
3
   2.7%
White
6
 100.0%
7
 100.0%
25
  86.2%
63
  91.3%
101
  91.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
   3.4%
3
   4.3%
4
   3.6%
Baseline (Day 1) Karnofsky Performance Score (KPS)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 7 participants 29 participants 69 participants 111 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]
Measure Description: 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
1.Primary Outcome
Title Number of Participants That Experienced a Dose-limiting Toxicity (DLT)
Hide Description The primary outcome of Phase I of this trial was to determine the maximum tolerated dose (MTD) of ZD6474 (Vandetanib) in patients with newly-diagnosed glioblastomas multiforme (GBM) and gliosarcomas who are also receiving radiation therapy with concomitant and adjuvant temozolomide. The MTD is the dose level at which 0/6 or 1/6 patients experience a dose-limiting toxicity (DLT) with the next higher dose having at least 2/3 or 2/6 patients encountering DLT.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
This measure was only assessed in Participants enrolled into the Phase I part of the study who had available data for analysis.
Arm/Group Title 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)
Hide Arm/Group Description:

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.

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.

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].

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.

Overall Number of Participants Analyzed 6 6 0 0
Measure Type: Number
Unit of Measure: Participants
3 0
2.Primary Outcome
Title Median Overall Survival (OS) of Phase II Patients
Hide Description The primary outcome of Phase II of this trial was to determine the efficacy of ZD6474 (Vandetanib) in combination with radiation therapy and concomitant and adjuvant temozolomide in patients with newly-diagnosed GBM and gliosarcomas as measured by overall survival and median survival.
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
This measure was only assessed in Participants in Phase II part of the study, who had available data for analysis
Arm/Group Title 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)
Hide Arm/Group Description:

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.

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.

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].

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.

Overall Number of Participants Analyzed 0 0 29 69
Median (95% Confidence Interval)
Unit of Measure: months
15.9
(11.0 to 22.5)
16.6
(14.9 to 20.1)
3.Secondary Outcome
Title Median Progression-free Survival (PFS), as Calculated by the # of Months Patients Remain Progression-free
Hide Description A secondary outcome of Phase II of this trial is the median progression-free survival (PFS), as calculated by the # of months patients remain progression-free
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
This is an outcome for Phase II participants only; 0 Phase I participants were included in the analysis.
Arm/Group Title 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)
Hide Arm/Group Description:

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.

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.

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].

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.

Overall Number of Participants Analyzed 0 0 29 69
Median (95% Confidence Interval)
Unit of Measure: months
6.2
(3.9 to 10.4)
7.7
(5.5 to 10.1)
4.Secondary Outcome
Title PHASE II: Percentage of Grade 3-5 Treatment-Related Adverse Events
Hide Description The percentage of adverse events (based on CTCAEv3) reported on study (via case report forms and Reportable AE submissions) that are both high-grade (grade 3, 4, or 5) and considered at least possibly related to study treatment.
Time Frame Adverse events experienced by participants are collected and reported throughout treatment with study drug (from initiation of study treatment until 30 days after the last dose of study treatment), maximum timeframe was 6 years.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase II - Arm A - Participants Phase II - Arm B - Participants
Hide Arm/Group Description:
Phase II Control Arm: Arm A (RT + TMZ)
Phase II Treatment Arm: Arm B (RT + TMZ + Vandetanib)
Overall Number of Participants Analyzed 29 69
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of events
4.16
(2.56 to 6.35)
8.37
(6.85 to 10.10)
5.Secondary Outcome
Title PHASE I: Percentage of Grade 3-5 Treatment-Related Adverse Events
Hide Description The percentage of adverse events (based on CTCAEv3) reported on study (via case report forms and Reportable AE submissions) that are both high-grade (grade 3, 4, or 5) and considered at least possibly related to study treatment.
Time Frame Adverse events experienced by participants are collected and reported throughout treatment with study drug (from initiation of study treatment until 30 days after the last dose of study treatment), maximum timeframe was 7 years.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I Participants - Vandetanib @ 200 mg/Day Phase I Participants - Vandetanib @ 100 mg/Day
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Phase I Participants (RT + TMZ + Vandetanib): Cohorts 1 & 2 (Vandetanib @ 200 mg/day)
Phase I Participants (RT + TMZ + Vandetanib): Cohorts 3 & 4 (Vandetanib @ 100 mg/day)
Overall Number of Participants Analyzed 6 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of events
9.48
(5.15 to 15.68)
4.43
(1.8 to 8.92)
Time Frame AEs & SAEs are collected from consent throughout tx period, including a follow-up period (30 days after last dose or until resolution). All study-related AEs are followed until resolution, unless deemed by the Investigator unlikely to resolve.
Adverse Event Reporting Description Although 29 pts received study tx in the Phase II - Arm A group, the # of pts at risk for SAEs in the "Phase II-Arm A Pts (Control Group): RT + TMZ" group is reported as 30 to include 1 additional Arm A pt who did not ultimately start study tx who experienced a Reportable AE (gr3 confusion w/ urinary incontinence) on the date pt was registered.
 
Arm/Group Title Phase I & Phase II-Arm B Pts: RT + TMZ + Vandetanib Phase II-Arm A Pts (Control Group): RT + TMZ
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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.

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].

All-Cause Mortality
Phase I & Phase II-Arm B Pts: RT + TMZ + Vandetanib Phase II-Arm A Pts (Control Group): RT + TMZ
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Phase I & Phase II-Arm B Pts: RT + TMZ + Vandetanib Phase II-Arm A Pts (Control Group): RT + TMZ
Affected / at Risk (%) Affected / at Risk (%)
Total   52/82 (63.41%)   15/30 (50.00%) 
Blood and lymphatic system disorders     
hemoglobin  1  2/82 (2.44%)  1/30 (3.33%) 
lymphopenia  1  8/82 (9.76%)  1/30 (3.33%) 
neutrophils  1  7/82 (8.54%)  3/30 (10.00%) 
platelets  1  4/82 (4.88%)  4/30 (13.33%) 
leukocytes  1  0/82 (0.00%)  0/30 (0.00%) 
blood/bone marrow: other: hemolytic anemia  1  1/82 (1.22%)  0/30 (0.00%) 
Cardiac disorders     
supraventricular and nodal arrhythmia: atrial fibrillation  1  1/82 (1.22%)  0/30 (0.00%) 
hypertension  1  1/82 (1.22%)  0/30 (0.00%) 
hypotension  1  1/82 (1.22%)  0/30 (0.00%) 
Endocrine disorders     
adrenal insufficiency  1  0/82 (0.00%)  1/30 (3.33%) 
Eye disorders     
vision-blurred  1  1/82 (1.22%)  0/30 (0.00%) 
Gastrointestinal disorders     
anorexia  1  0/82 (0.00%)  1/30 (3.33%) 
ascites (non-malignant)  1  1/82 (1.22%)  0/30 (0.00%) 
dehydration  1  0/82 (0.00%)  1/30 (3.33%) 
diarrhea w/o prior colostomy  1  1/82 (1.22%)  0/30 (0.00%) 
duodenum, hemorrhage  1  1/82 (1.22%)  0/30 (0.00%) 
fistula, colon/cecum/appendix  1  1/82 (1.22%)  0/30 (0.00%) 
nausea  1  1/82 (1.22%)  0/30 (0.00%) 
perforation, colon  1  2/82 (2.44%)  0/30 (0.00%) 
stomach, hemorrhage  1  1/82 (1.22%)  0/30 (0.00%) 
vomiting  1  1/82 (1.22%)  0/30 (0.00%) 
pain - abdomen NOS  1  2/82 (2.44%)  0/30 (0.00%) 
General disorders     
fatigue  1  1/82 (1.22%)  1/30 (3.33%) 
fever without neutropenia  1  3/82 (3.66%)  1/30 (3.33%) 
death - disease progression  1  1/82 (1.22%)  0/30 (0.00%) 
death NOS  1  1/82 (1.22%)  0/30 (0.00%) 
edema: head and neck (cerebral edema)  1  1/82 (1.22%)  0/30 (0.00%) 
pain - chest/thorax NOS  1  1/82 (1.22%)  0/30 (0.00%) 
Hepatobiliary disorders     
cholecystitis  1  1/82 (1.22%)  0/30 (0.00%) 
liver dysfunction/failure (clinical)  1  1/82 (1.22%)  0/30 (0.00%) 
Infections and infestations     
infection gr0-2 neut, appendix  1  1/82 (1.22%)  0/30 (0.00%) 
infection gr0-2 neut, lung  1  3/82 (3.66%)  0/30 (0.00%) 
infection gr0-2 neut, nose  1  1/82 (1.22%)  0/30 (0.00%) 
infection gr0-2 neut, skin  1  1/82 (1.22%)  0/30 (0.00%) 
infection gr0-2 neut, urinary tract  1  1/82 (1.22%)  2/30 (6.67%) 
infection gr0-2 neut, wound  1  1/82 (1.22%)  0/30 (0.00%) 
infection w/ gr3-4 neut, wound  1  1/82 (1.22%)  0/30 (0.00%) 
infection gr0-2 neut, anal/perianl  1  0/82 (0.00%)  1/30 (3.33%) 
infection: other: eye infection  1  0/82 (0.00%)  1/30 (3.33%) 
infection: other: infection of the leg  1  1/82 (1.22%)  0/30 (0.00%) 
Metabolism and nutrition disorders     
ALT, SGPT  1  3/82 (3.66%)  0/30 (0.00%) 
AST, SGOT  1  3/82 (3.66%)  0/30 (0.00%) 
bilirubin  1  1/82 (1.22%)  0/30 (0.00%) 
hyperglycemia  1  1/82 (1.22%)  1/30 (3.33%) 
hypophosphatemia  1  1/82 (1.22%)  0/30 (0.00%) 
metabolic/laboratory: other: immunosupression  1  1/82 (1.22%)  0/30 (0.00%) 
Musculoskeletal and connective tissue disorders     
nonneuropathic generalized weakness  1  1/82 (1.22%)  0/30 (0.00%) 
nonneuropathic left-side muscle weak  1  1/82 (1.22%)  0/30 (0.00%) 
musculoskeletal/soft tissue: other: steroid myopathy  1  1/82 (1.22%)  0/30 (0.00%) 
extremity-lower (gait/walking)  1  0/82 (0.00%)  1/30 (3.33%) 
musculoskeletal/soft tissue: other: bulging discs  1  0/82 (0.00%)  1/30 (3.33%) 
pain - muscle  1  1/82 (1.22%)  0/30 (0.00%) 
Nervous system disorders     
CNS, hemorrhage  1  1/82 (1.22%)  0/30 (0.00%) 
CNS cerebrovascular ischemia  1  1/82 (1.22%)  0/30 (0.00%) 
confusion  1  1/82 (1.22%)  2/30 (6.67%) 
dizziness  1  1/82 (1.22%)  0/30 (0.00%) 
mental status  1  1/82 (1.22%)  0/30 (0.00%) 
neuropathy-motor  1  1/82 (1.22%)  0/30 (0.00%) 
neuropathy-sensory  1  1/82 (1.22%)  0/30 (0.00%) 
neurology: other: vasogenic cerebral edema  1  1/82 (1.22%)  0/30 (0.00%) 
seizure  1  6/82 (7.32%)  2/30 (6.67%) 
speech impairment (e.g., dysphasia or aphasia)  1  2/82 (2.44%)  1/30 (3.33%) 
syncope (fainting)  1  1/82 (1.22%)  0/30 (0.00%) 
cognitive disturbance  1  0/82 (0.00%)  1/30 (3.33%) 
pain - head/headache  1  1/82 (1.22%)  0/30 (0.00%) 
Renal and urinary disorders     
obstruction-ureteral  1  1/82 (1.22%)  0/30 (0.00%) 
renal failure  1  1/82 (1.22%)  0/30 (0.00%) 
urinary retention  1  2/82 (2.44%)  1/30 (3.33%) 
incontinence, urinary  1  0/82 (0.00%)  1/30 (3.33%) 
Respiratory, thoracic and mediastinal disorders     
hemorrhage, pulmonary/upper respiratory: nose  1  1/82 (1.22%)  0/30 (0.00%) 
pain - throat/pharynx/larynx  1  1/82 (1.22%)  0/30 (0.00%) 
cough  1  1/82 (1.22%)  0/30 (0.00%) 
dyspnea  1  2/82 (2.44%)  1/30 (3.33%) 
hypoxia  1  2/82 (2.44%)  0/30 (0.00%) 
obstruction, airway-bronchus  1  1/82 (1.22%)  0/30 (0.00%) 
pleural effusion (non-malignant)  1  1/82 (1.22%)  0/30 (0.00%) 
pneumonitis/pulmonary infiltrates  1  1/82 (1.22%)  0/30 (0.00%) 
Skin and subcutaneous tissue disorders     
erythema multiforme  1  1/82 (1.22%)  0/30 (0.00%) 
rash/desquamation  1  1/82 (1.22%)  0/30 (0.00%) 
rash: acne/acneiform  1  1/82 (1.22%)  0/30 (0.00%) 
wound - non-infectious  1  1/82 (1.22%)  0/30 (0.00%) 
Vascular disorders     
hematoma  1  0/82 (0.00%)  1/30 (3.33%) 
thrombosis/thrombus/embolism  1  18/82 (21.95%)  5/30 (16.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase I & Phase II-Arm B Pts: RT + TMZ + Vandetanib Phase II-Arm A Pts (Control Group): RT + TMZ
Affected / at Risk (%) Affected / at Risk (%)
Total   81/82 (98.78%)   28/29 (96.55%) 
Blood and lymphatic system disorders     
hemoglobin  1  38/82 (46.34%)  19/29 (65.52%) 
leukocytes  1  34/82 (41.46%)  12/29 (41.38%) 
lymphopenia  1  43/82 (52.44%)  16/29 (55.17%) 
neutrophils  1  21/82 (25.61%)  9/29 (31.03%) 
platelets  1  48/82 (58.54%)  13/29 (44.83%) 
blood/bone marrow: other: decreased hematocrit  1  6/82 (7.32%)  1/29 (3.45%) 
blood/bone marrow: other: decreased red blood cells  1  3/82 (3.66%)  2/29 (6.90%) 
blood/bone marrow: other: increase eosinophils  1  2/82 (2.44%)  2/29 (6.90%) 
Endocrine disorders     
cushingnoid appearance  1  5/82 (6.10%)  5/29 (17.24%) 
adrenal insufficiency  1  0/82 (0.00%)  2/29 (6.90%) 
Eye disorders     
vision - blurred  1  6/82 (7.32%)  3/29 (10.34%) 
Gastrointestinal disorders     
anorexia  1  16/82 (19.51%)  9/29 (31.03%) 
constipation  1  17/82 (20.73%)  9/29 (31.03%) 
diarrhea w/o prior colostomy  1  25/82 (30.49%)  2/29 (6.90%) 
dyspepsia  1  9/82 (10.98%)  2/29 (6.90%) 
nausea  1  33/82 (40.24%)  11/29 (37.93%) 
taste disturbance  1  6/82 (7.32%)  1/29 (3.45%) 
vomiting  1  17/82 (20.73%)  4/29 (13.79%) 
dehydration  1  2/82 (2.44%)  2/29 (6.90%) 
pain, abdomen, NOS  1  6/82 (7.32%)  2/29 (6.90%) 
General disorders     
fatigue  1  62/82 (75.61%)  22/29 (75.86%) 
edema, head and neck  1  0/82 (0.00%)  3/29 (10.34%) 
edema, limb  1  10/82 (12.20%)  5/29 (17.24%) 
Infections and infestations     
infection gr0-2 neut, oral cavity  1  5/82 (6.10%)  3/29 (10.34%) 
infection gr0-2 neut, conjunctiva  1  0/82 (0.00%)  3/29 (10.34%) 
infection gr0-2 neut, upper airway  1  3/82 (3.66%)  2/29 (6.90%) 
infection gr0-2 neut, urinary tract  1  4/82 (4.88%)  3/29 (10.34%) 
Investigations     
PTT  1  5/82 (6.10%)  1/29 (3.45%) 
weight loss  1  7/82 (8.54%)  2/29 (6.90%) 
Metabolism and nutrition disorders     
alkaline phosphatase  1  11/82 (13.41%)  3/29 (10.34%) 
ALT, SGPT  1  48/82 (58.54%)  15/29 (51.72%) 
AST, SGOT  1  37/82 (45.12%)  10/29 (34.48%) 
bicarbonate  1  17/82 (20.73%)  8/29 (27.59%) 
bilirubin  1  17/82 (20.73%)  4/29 (13.79%) 
creatinine  1  18/82 (21.95%)  2/29 (6.90%) 
hypercalcemia  1  7/82 (8.54%)  1/29 (3.45%) 
hyperglycemia  1  50/82 (60.98%)  19/29 (65.52%) 
hyperkalemia  1  18/82 (21.95%)  5/29 (17.24%) 
hypermagnesemia  1  7/82 (8.54%)  4/29 (13.79%) 
hypernatremia  1  6/82 (7.32%)  2/29 (6.90%) 
hypoalbuminemia  1  19/82 (23.17%)  3/29 (10.34%) 
hypocalcemia  1  19/82 (23.17%)  4/29 (13.79%) 
hypoglycemia  1  17/82 (20.73%)  2/29 (6.90%) 
hypokalemia  1  17/82 (20.73%)  7/29 (24.14%) 
hypomagnesemia  1  6/82 (7.32%)  4/29 (13.79%) 
hyponatremia  1  25/82 (30.49%)  5/29 (17.24%) 
hypophosphatemia  1  22/82 (26.83%)  7/29 (24.14%) 
proteinuria  1  17/82 (20.73%)  5/29 (17.24%) 
hyperuricemia  1  0/82 (0.00%)  2/29 (6.90%) 
metabolic/laboratory: other: elevated BUN  1  3/82 (3.66%)  2/29 (6.90%) 
metabolic/laboratory: other: hyperphosphatemia  1  1/82 (1.22%)  2/29 (6.90%) 
Musculoskeletal and connective tissue disorders     
extremity-lower (gait/walking)  1  5/82 (6.10%)  2/29 (6.90%) 
nonneuropathic generalized weakness  1  9/82 (10.98%)  2/29 (6.90%) 
nonneuropathic left-side muscle weak  1  5/82 (6.10%)  1/29 (3.45%) 
nonneuropathic lower extr muscle weak  1  8/82 (9.76%)  2/29 (6.90%) 
pain, back  1  5/82 (6.10%)  4/29 (13.79%) 
pain, extremity-limb  1  6/82 (7.32%)  1/29 (3.45%) 
pain, joint  1  5/82 (6.10%)  2/29 (6.90%) 
Nervous system disorders     
anxiety  1  14/82 (17.07%)  4/29 (13.79%) 
ataxia  1  7/82 (8.54%)  3/29 (10.34%) 
cognitive disturbance  1  6/82 (7.32%)  6/29 (20.69%) 
confusion  1  14/82 (17.07%)  4/29 (13.79%) 
depression  1  19/82 (23.17%)  2/29 (6.90%) 
dizziness  1  15/82 (18.29%)  6/29 (20.69%) 
memory impairment  1  20/82 (24.39%)  7/29 (24.14%) 
neuropathy CN II vision  1  6/82 (7.32%)  0/29 (0.00%) 
neuropathy-motor  1  7/82 (8.54%)  2/29 (6.90%) 
neuropathy-sensory  1  11/82 (13.41%)  4/29 (13.79%) 
seizure  1  11/82 (13.41%)  5/29 (17.24%) 
speech impairment  1  8/82 (9.76%)  6/29 (20.69%) 
tremor  1  12/82 (14.63%)  4/29 (13.79%) 
personality  1  0/82 (0.00%)  2/29 (6.90%) 
pain, head/headache  1  29/82 (35.37%)  16/29 (55.17%) 
Psychiatric disorders     
insomnia  1  20/82 (24.39%)  1/29 (3.45%) 
Renal and urinary disorders     
urinary frequency/urgency  1  11/82 (13.41%)  4/29 (13.79%) 
incontinence urinary  1  4/82 (4.88%)  3/29 (10.34%) 
Respiratory, thoracic and mediastinal disorders     
hemorrhage, pulmonary/upper respiratory: nose  1  3/82 (3.66%)  2/29 (6.90%) 
cough  1  17/82 (20.73%)  1/29 (3.45%) 
dyspnea  1  7/82 (8.54%)  7/29 (24.14%) 
Skin and subcutaneous tissue disorders     
alopecia  1  18/82 (21.95%)  6/29 (20.69%) 
chemoradiation dermatitis  1  5/82 (6.10%)  2/29 (6.90%) 
erythema multiforme  1  6/82 (7.32%)  0/29 (0.00%) 
pruritus/itching  1  7/82 (8.54%)  0/29 (0.00%) 
rash/desquamation  1  23/82 (28.05%)  2/29 (6.90%) 
rash: acne/acneiform  1  17/82 (20.73%)  3/29 (10.34%) 
dry skin  1  4/82 (4.88%)  3/29 (10.34%) 
radiation dermatitis  1  3/82 (3.66%)  4/29 (13.79%) 
Vascular disorders     
thrombosis/thrombus/embolism  1  18/82 (21.95%)  4/29 (13.79%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
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.
Results Point of Contact
Name/Title: Dr. Eudocia Quant Lee
Organization: Dana-Farber Cancer Institute
Phone: 617-632-2166
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 ( Other Identifier: AstraZeneca )
First Submitted: February 27, 2007
First Posted: February 28, 2007
Results First Submitted: February 5, 2015
Results First Posted: March 2, 2015
Last Update Posted: March 5, 2019