Phase I / II Adaptive Randomized Trial of Vorinostat, Erlotinib and Temozolomide in Adults With Recurrent Glioblastoma Multiforme
Phase I:
The Study Drugs:
Vorinostat is designed to cause chemical changes in different groups of proteins that are
attached to DNA (the genetic material of cells), which may slow the growth of cancer cells
or cause the cancer cells to die.
Erlotinib is designed to block the activity of a protein found on the surface of many tumor
cells that may control tumor growth and survival. This may stop tumors from growing.
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:
There are 2 phases to this study.
If you are found to be eligible to take part in the Phase I portion of this study, you will
be assigned to 1 of 2 groups based on when you join this study. You will remain in the same
group for the entire study. In this study, the dose level of the study drugs is different
from group to group. Up to 4 dose levels of study drug combinations will be tested in Group
1, up to 2 dose levels in Group 2. Three (3) participants will be enrolled at each dose
level. The first 3 participants in each group will receive the lowest dose level. Each 3
new participants will receive a higher dose than the one before it, if no intolerable side
effects were seen. This will continue until the highest tolerable dose of study drugs given
in combination is found.
- If you are in Group 1, you will take vorinostat, erlotinib, and temozolomide.
- If you are in Group 2, you will take vorinostat and erlotinib.
In addition, no matter which group or dose level you are assigned to, if you are on enzyme
inducing anti-seizure drug, you will take a higher dose of erlotinib.
Study Drug Administration:
Each study cycle is 28 days.
If you are in Group 1:
- On Days 1-7 and 15-21 of every cycle, you will take vorinostat by mouth 2 times a day.
You should take vorinostat with food. Do not open, crush, or chew the capsules.
- On Days 1-21 of every cycle, you will take erlotinib by mouth 1 time a day. You should
take erlotinib in the morning 1 hour before or 2 hours after food with 1 cup (about 8
oz.) of water.
- On Days 1-7 and 15-21of every cycle, you will take the temozolomide by mouth 1 time a
day. You should swallow the temozolomide capsules 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 ounces) of water.
If you are in Group 2:
- On Days 1-14 of every cycle, you will take vorinostat by mouth 2 times a day. You
should take vorinostat with food. Do not open, crush, or chew the capsules.
- On Days 1-21 of every cycle, you will take erlotinib by mouth 1 time a day. You should
take erlotinib in the morning 1 hour before or 2 hours after food with 1 cup (about 8
oz.) of water.
Study Visits:
Every 4 weeks for the first 8 weeks, then every 8 weeks after that:
- Your complete medical history will be recorded.
- You will be asked about any drugs you may be taking and if you have experienced any
side effects.
- You will have a physical exam, including measurement of your vital signs and weight.
- You will have a neurological exam.
- Your performance status will be recorded.
Every week for the first 4 weeks, then every 2 weeks after that, blood (about 3 teaspoons)
will be drawn for routine tests and to check your blood's ability to clot normally.
Every 4 weeks, if you are on anti-seizure drugs, blood (about 1 teaspoon) will be drawn to
measure the amount of anti-seizure drugs in your blood.
Every 8 weeks, you will have an MRI scan to check the status of the disease.
Length of Study:
You will be on study for up to 1 year. You may continue to receive the study drugs beyond 1
year and remain on study if your doctor decides that it is in your best interest. You will
be taken off study early if the disease gets worse or you experience intolerable side
effects.
Long-Term Follow-Up Visit:
If you go off study after 12 cycles, blood (about 3 teaspoons) will be drawn for routine
tests and to check your blood's ability to clot normally every 2 weeks during the 30 days
after your last dose of study drugs.
If you go off the study for reasons other than the worsening of the disease, you will have
an MRI every 2 months unless the disease gets worse.
If you have an MRI that shows worsening of the disease, every 2-3 months from then on, you
may be called and asked how you are feeling and about any new cancer treatment that you may
have received. This phone call should take about 5-10 minutes.
This is an investigational study. Erlotinib is FDA approved drug for treatment of some
types of non-small cell lung cancer, temozolomide for some types of brain cancer, and
vorinostat for some types of lymphoma. All are commercially available. The use of these
drugs in this combination is investigational.
Up to 182 participants will take part in this study. Up to 72 patients will be enroll in the
Phase 1 portion of this study. All will be enrolled at MD Anderson.
Phase II:
The Study Drugs:
Vorinostat is designed to cause chemical changes in different groups of proteins that are
attached to DNA (the genetic material of cells), which may slow the growth of cancer cells
or cause the cancer cells to die.
Erlotinib is designed to block the activity of a protein found on the surface of many tumor
cells that may control tumor growth and survival. This may stop tumors from growing.
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:
There are 2 phases to this study.
If you are found to be eligible to take part in the Phase 2 portion of this study, you will
be randomly assigned (as in the roll of the dice) to 1 of 2 groups.
- If you are in Group 1, you will take vorinostat and erlotinib.
- If you are in Group 2, you will take vorinostat, erlotinib, and temozolomide.
Subset Group:
If your doctor has recommended that you have surgery to remove a tumor that has come back,
you will be eligible for this subset group. You would have the surgery before being assigned
to a main study group. This subset group of the study is done to learn the effects of
vorinostat on tumor tissue and blood cells.
Before surgery, you will be randomly assigned to 1 of 3 groups.
- If you are in Group A, you will receive vorinostat alone.
- If you are in Group B, you will receive erlotinib alone.
- If you are in Group C, you will receive both vorinostat and erlotinib.
You will take the study drug(s) for 3 days in a row before your surgery.
About 2 weeks after the surgery, you will be randomly assigned to 1 of 2 main study groups
described above (Group 1 or 2).
In addition, no matter which group you are assigned to, if you are on enzyme inducing
anti-seizure drug, you will take the higher dose of erlotinib.
Study Drug Administration:
Every cycle is 28 days.
If you are in Group 1:
- On Days 1-14 of every cycle, you will take vorinostat by mouth 2 times a day. You
should take vorinostat with food. Do not open, crush, or chew the capsules.
- On Days 1-21 of every cycle, you will take erlotinib by mouth 1 time a day. You should
take erlotinib in the morning 1 hour before or 2 hours after food with 1 cup (about 8
oz.) of water.
If you are in Group 2:
- On Days 1-7 and 15-21 of every cycle, you will take vorinostat by mouth 2 times a day
.You should take vorinostat with food. Do not open, crush, or chew the capsules.
- On Days 1-21 of every cycle, you will take erlotinib by mouth 1 time a day . You should
take erlotinib in the morning 1 hour before or 2 hours after food with 1 cup (about 8
oz.) of water.
- On Days 1-7 and 15-21 of every cycle, you will take the temozolomide by mouth 1 time a
day. You should swallow the temozolomide capsules 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 ounces) of water.
Subset group:
For 3 days in row before surgery:
- If you are in Group A, you will take vorinostat by mouth 2 times a day.
- If you are in Group B, you will take erlotinib by mouth 1 time a day.
- If you are in Group C, you will take vorinostat by mouth 2 time a day and erlotinib by
mouth 1 time a day.
After you have recovered from the effects of surgery (about 2 weeks), you will follow the
study group schedule (Group 1 or 2) described above.
Study Visits
Every 4 weeks for the first 8 weeks, then every 8 weeks after that:
- Your complete medical history will be recorded.
- You will be asked about any drugs you may be taking and if you have had any side
effects.
- You will have a physical exam, including measurement of your vital signs and weight.
- You will have a neurological exam.
- Your performance status will be recorded.
Every week for the first 4 weeks, then every 2 weeks after that, blood (about 3 teaspoons)
will be drawn for routine tests and to check your blood's ability to clot normally.
Every 4 weeks, if you are on anti-seizure medications, blood (about 1 teaspoon) will be
drawn to measure the amount of anti-seizure medications in your blood.
Every 8 weeks, you will have an MRI scan to check the status of the disease.
Subset Group:
In addition to the above tests, blood (about 1 teaspoon each time) will be drawn 1 time
before and 3 times after the first dose of vorinostat, and during surgery. This blood will
be used to study the drug levels, the effects of the drug in normal blood cells, and to
match these findings with that in the tumor.
After the surgery, part of the leftover tumor tissue from the surgery will be used to
measure the drug levels and the effects of vorinostat on the tumor and be used for biomarker
tests.
Length of Study:
You will be on study for up to 1 year. You may continue to receive treatment beyond 1 year
and remain on study if your doctor decides that it is in your best interest. You will be
taken off study early if the disease gets worse or you have intolerable side effects.
Long-Term Follow-Up Visit:
If you go off study after 12 cycles, blood (about 3 teaspoons) will be drawn for routine
tests and to check your blood's ability to clot normally every 2 weeks during the 30 days
after your last dose of study drugs.
If you go off the study for reasons other than the worsening of the disease, you will have
an MRI every 2 months unless the disease gets worse.
If you have an MRI that shows worsening of the disease, every 2-3 months from then on, you
may be called and asked how you are feeling and about any new cancer treatment that you may
have received. This phone call will take about 5-10 minutes.
This is an investigational study. Erlotinib is FDA approved drug for treatment of some
types of non-small cell lung cancer, temozolomide for some types of brain cancer, and
vorinostat for some types of lymphoma. All are commercially available. The use of these
drugs in this combination is investigational.
Up to 182 participants will take part in this study. Up to 110 patients will be enrolled in
the Phase 2 portion of this study. Up to 15 participants will take part in the subset
portion of the study. All will be enrolled at MD Anderson.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD)
Evaulated with each 28 day (+2 days) cycle
Yes
John DeGroot, MD
Principal Investigator
UT MD Anderson Cancer Center
United States: Institutional Review Board
2009-0651
NCT01110876
June 2011
Name | Location |
---|---|
UT MD Anderson Cancer Center | Houston, Texas 77030 |