Glioblastoma Clinical Trial
Official title:
Phase I/II Trial of Dasatinib (Sprycel) With Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma
Phase I:
Primary Objectives:
-To define the maximum tolerated dose (MTD) of dasatinib (Sprycel) with radiotherapy (RT) and
6 weeks of concomitant temozolomide (TMZ) administered at 75 mg/m^2/day in patients with
newly-diagnosed glioblastoma (GBM).
Secondary Objectives:
- To characterize the safety profile of dasatinib (Sprycel) in combination with
radiotherapy (RT) and concomitant TMZ in patients with newly-diagnosed GBM.
- To characterize the safety profile of dasatinib (Sprycel) in combination with adjuvant
TMZ in patients with glioblastoma after RT.
STUDY DID NOT PROGRESS TO PHASE II PORTION.
Phase II:
Primary Objectives:
-To determine the effectiveness of dasatinib (Sprycel) with radiotherapy (RT) and 6 weeks of
concomitant temozolomide (TMZ) administered at 75 mg/m^2/day followed by adjuvant
temozolomide with concurrent dasatinib in patients with newly-diagnosed glioblastoma (GBM) as
measured by overall survival.
Secondary Objectives:
- To determine the efficacy of this treatment as measured by radiographic response (RR),
progression-free survival (PFS) and time to progression (TTP).
- To characterize the safety profile of dasatinib (Sprycel) in combination with RT and
concomitant TMZ in patients with newly-diagnosed GBM.
- To characterize the safety profile of dasatinib (Sprycel) in combination with adjuvant
TMZ in patients with GBM after RT.
Exploratory Objectives:
-To correlate tumor genotype, tumor expression of dasatinib target proteins (e.g. Src, EphA2,
c-kit and PDGFR), and PTEN levels with response to therapy with dasatinib and temozolomide.
PHASE I
The Study Drugs:
Dasatinib is designed to change the function of certain genes. By changing the function of
these genes, it may prevent cancer from growing and spreading. It is also designed to block
or lower the activity of one or more tumor-causing proteins responsible for the uncontrolled
growth of tumor cells, which may result in shrinking or stopping tumor growth.
Temozolomide is designed to kill cancer cells by damaging DNA (the genetic material of
cells). The damaged DNA may cause tumor cell death.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose
level of dasatinib based on when you joined this study. Up to 2 dose levels of dasatinib will
be tested. Three (3) participants will be enrolled at each dose level. The first group of
participants will receive the lowest dose level. Each new group will receive a higher dose
than the group before it, if no intolerable side effects were seen. This will continue until
the highest tolerable dose of dasatinib given in combination with temozolomide is found.
All the groups will take the same dose level of temozolomide for the entire study.
The amount of study drugs you receive may change if you experience side effects. If at any
time you experience any intolerable side effects, tell the study doctor right away.
Study Drug Administration:
During Radiation:
As a part of standard of care, you will receive radiation therapy Monday-Friday for a total
of 30 radiation treatments (about 6 weeks).
Every day while you are receiving radiation, you will take the temozolomide by mouth once a
day for up to a maximum of 7 weeks.
You should swallow temozolomide whole, one right after the other, without chewing them. If
you vomit while taking temozolomide, you cannot take more capsules before the next scheduled
dose. They should be taken on an empty stomach (at least 1 hour before and 2 hours after
eating) with 1 cup (about 8 oz.) of water.
Every day while you are receiving radiation, you will take dasatinib by mouth 1 time a day
for up to a maximum of 7 weeks. You should take dasatinib without food (1 hour before or 2
hours after eating), with at least 1 cup (8 oz.) of water.
After Radiation:
After the radiation therapy ends, every day, you will continually take dasatinib by mouth 1
time a day.
You will not take temozolomide for about 4 weeks after the radiation therapy ends. After 4
weeks, you will begin taking temozolomide 1 time a day, by mouth, on Days 1-5 of each 28 day
study cycle.
Study Visits:
Four (4) weeks after the end of radiation, then every 4 weeks after that, the following tests
and procedures will be performed:
- You will have a physical exam, including measurement of your vital signs.
- You will have a neurological exam.
- You will have a performance status evaluation.
- You will be asked about any drugs you may be taking and if you have experienced any side
effects.
- Blood (about 1 teaspoon) will be drawn to check your blood's ability to clot normally.
Every week for the first 6 weeks, then every 4 weeks after that, you will be asked if you
have experienced any side effects.
If you are taking an anti-seizure drug, every 2 weeks for the first 6 weeks and then every 4
weeks after that, blood (about 1 teaspoon) will be drawn to check the levels of anti-seizure
drug in your blood.
At Week 6, then before each cycle after radiation for the first 6 cycles, you will have an
ECG.
Every week for the first 6 weeks, then on Days 1 and 22 of every cycle after radiation, blood
(about 3 teaspoons) will be collected for routine tests.
Four (4) weeks after the end of radiation, then every 8 weeks after that, you will have an
MRI scan to check the status of the disease.
Length of Study:
You may continue taking temozolomide for up to 12 cycles. You may continue taking dasatinib
for as long as you are benefitting. You will be taken off study early if the disease gets
worse or you experience intolerable side effects.
End-of-Study Visit:
After you go off study, you will have an end-of-study visit. At this visit, the following
tests and procedures will be performed:
- Your complete medical history will be recorded.
- You will have a physical exam.
- You will have a performance status evaluation.
- You will be asked about any drugs you may be taking and if you have experienced any side
effects.
- You will have a neurological exam.
- Blood (about 3 1/2 teaspoons) will be collected for routine tests and to check your
blood's ability to clot normally.
- If you are taking an anti-seizure drug, blood (about 1 teaspoon) will be drawn to check
the level of anti-seizure drug in your blood.
Long-Term Follow-up visit:
After the end-of-study visit, the study team/staff will contact you by telephone every 3
months to check how you are doing. Each phone call will take about 5 minutes.
This is an investigational study. Temozolomide is FDA approved and commercially available for
the treatment of brain tumors. Dasatinib is FDA approved and commercially available for the
treatment of some types of leukemia, but it is experimental for use in brain tumors. In
addition, the combination of temozolomide and dasatinib is experimental for use in brain
tumors. At this time, the combination is only being used in research.
Up to 72 participants will take part in this study. Up to 72 will be enrolled at M. D.
Anderson.
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