A Phase I/ Randomized Phase II Study of Gemcitabine Plus Erlotinib Plus MK-0646; Gemcitabine Plus MK-0646 and Gemcitabine Plus Erlotinib for Patients With Advanced Pancreatic Cancer (IISP#33337)
A Phase I/ Randomized Phase II Study of Gemcitabine Plus Erlotinib Plus MK-0646; Gemcitabine Plus MK-0646 and Gemcitabine Plus Erlotinib for Patients With Advanced Pancreatic Cancer (IISP#33337)
Objectives:
Primary Objectives:
Phase I: Determine the maximal tolerated dose (MTD) of MK-0646 in combination with gemcitabine or gemcitabine plus erlotinib and recommended phase II dose.
Phase II:
Secondary Objectives:
Phase I
The Study Drugs:
MK-0646 is designed to block proteins that are thought to cause cancer cells to grow and spread. This drug may help slow the growth of tumors.
Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells to die.
Erlotinib hydrochloride is designed to block the activity of a protein found on the surface of many tumor cells that may control the growth and survival of cancer cells. This may stop cancer cells from growing.
Study Drug Dose Level and Groups:
If you are found to be eligible to take part in this study, you will be assigned to a group (Arm A or Arm B) based on when you joined the study, how many participants have been enrolled before you, and on the safety data that is available at that time.
There are 2 dose levels of MK-0646 in each arm. There will be 3-6 participants enrolled in each dose level in each arm. Enrollment will begin in Arm A. Arm B will use the same 2 dose levels as Arm A. If the first dose level of Arm A is found to be tolerable, at least 3 patients will be enrolled in Arm B, Level 1, and then at least 3 patients will be enrolled in Arm A, Level 2. If Arm B, Level 1 and Arm A, Level 2 can be safely given, the last group of 3-6 patients will be enrolled in Arm B, Level 2. The first group of participants in each arm will receive the lower dose level. The next group in each arm will receive a higher dose than the first group, if no intolerable side effects were seen.
The dose of gemcitabine and/or erlotinib hydrochloride will be the same for every group.
Study Drug Administration:
If you are in Arm A, on Days 1, 8, and 15 of each 28-day study cycle, you will receive gemcitabine through a needle into your vein over about 1 1/2 hours. On Days 1, 8, 15, and 22 of each cycle, you will receive MK-0646 by vein over 1 hour.
If you are in Arm B, you will take erlotinib hydrochloride by mouth once a day (in the morning) every day. You should take it with about 1 cup (8 oz.) of water 1 hour before or 2 hours after eating. On Days 1, 8, and 15 of each cycle, you will receive gemcitabine by vein over about 1 1/2 hours. On Days 1, 8, 15, and 22 of each cycle, you will receive MK-0646 by vein over 1 hour.
Depending upon how well you tolerate gemcitabine, your doctor may decide that you should receive gemcitabine on Days 1 and 15 instead of Days 1, 8, and 15.
Study Visits:
On Day 1 of Cycle 1, the following tests and procedures will be performed:
On Day 8 of Cycle 1, the following tests and procedures will be performed:
On Day 15 of Cycle 1, the following tests and procedures will be performed:
On Day 22 of Cycle 1, the following tests and procedures will be performed:
On Day 1 of Cycles 2 and beyond, the following tests and procedures will be performed:
On Days 8 and 15 of Cycles 2 and beyond, the following tests and procedures will be performed:
On Day 22 of Cycles 2 and beyond, your vital signs and weight will be measured and you will be asked if you have experienced any side effects.
On Day 22 of Cycle 2 and every even cycle (Cycles 4, 6, 8, and so on), you will have a CT scan or MRI scan to check the status of the disease. Blood (about 1 teaspoon) will also be drawn to test HAHA.
Length of Study:
You may remain on study for as long as you are benefiting. You will be taken off study 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:
At Weeks 4, 8, and 12 after the end of study visit, blood (about 1 teaspoon) will be drawn to test HAHA.
Long-Term Follow Up:
Once you are off study, every 3 months from then on, the study staff will ask you how you are doing, either in the clinic or by telephone. If you are called, the phone call will take about 10-15 minutes.
This is an investigational study. MK-0646 is not FDA approved or commercially available. At this time, MK-0646 is only being used in research. Gemcitabine is FDA approved and commercially available for the treatment of pancreatic cancer. Erlotinib hydrochloride is FDA approved and commercially available for the treatment of pancreatic cancer in combination with gemcitabine.
Up to 100 patients will take part in this study. All will be enrolled at MD Anderson.
Phase II:
The Study Drugs:
MK-0646 is designed to block proteins that are thought to cause cancer cells to grow and spread. This drug may help slow the growth of tumors.
Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells to die.
Erlotinib hydrochloride is designed to block the activity of a protein found on the surface of many tumor cells that may control the growth and survival of cancer cells. This may stop cancer cells from growing.
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of the dice) into 1 of 3 groups.
Study Drug Administration:
If you are in Arm A, on Days 1, 8, and 15 of each 28-day study cycle, you will receive gemcitabine through a needle into your vein over about 1 1/2 hours as an infusion once a week for 3 weeks. On Days 1, 8, 15, and 22 of each cycle, you will receive MK-0646 by vein over 1 hour.
If you are in Arm B, you will take erlotinib hydrochloride by mouth once (in the morning) every day. On Days 1, 8, and 15 of each cycle, you will receive gemcitabine by vein over about 1 1/2 hours. On Days 1, 8, 15, and 22 of each cycle, you will receive MK-0646 by vein over 1 hour.
If you are in Arm C, you will take erlotinib hydrochloride by mouth once (in the morning) every day. On Days 1, 8, and 15 of each cycle, you will receive gemcitabine by vein over about 1 1/2 hours.
If you are taking erlotinib hydrochloride, you should take it with about 1 cup (8 oz.) of water 1 hour before or 2 hours after eating.
Depending upon how well you tolerate gemcitabine, your doctor may decide that you should receive gemcitabine on Days 1 and 15 instead of Days 1, 8, and 15.
Study Visits:
On Day 1 of Cycle 1, the following tests and procedures will be performed:
On Day 8 of Cycle 1, the following tests and procedures will be performed:
On Day 15 of Cycle 1, the following tests and procedures will be performed:
On Day 22 of Cycle 1, the following tests and procedures will be performed if you are receiving MK-0646:
On Day 1 of Cycles 2 and beyond, the following tests and procedures will be performed:
On Days 8 and 15 of Cycles 2 and beyond, the following tests and procedures will be performed:
On Day 22 of Cycles 2 and beyond, your vital signs and weight will be measured, (if you are receiving MK-0646). and you will be asked if you have experienced any side effects.
On Day 22 of Cycle 2 and every even cycle (Cycles 4, 6, 8, and so on), you will have a CT scan or MRI scan to check the status of the disease. Blood (about 1 teaspoon) will be also be drawn to test HAHA if you are receiving MK-0646.
Length of Study:
You may remain on study for as long as you are benefiting. You will be taken off study if the disease gets worse or you experience intolerable side effects.
If you are in Arm C (erlotinib and gemcitabine) and the disease gets worse, you may be allowed to join Arm B (gemcitabine, erlotinib, and MK-0646).
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:
At Weeks 4, 8, and 12 after the end of study visit, blood (about 1 teaspoon) will be drawn to test HAHA if you were receiving MK-0646.
Long-Term Follow Up:
Once you are off study, every 3 months from then on, the study staff will ask you how you are doing, either in the clinic or by telephone. If you are called, this phone call will take about 10-15 minutes.
This is an investigational study. MK-0646 is not FDA approved or commercially available. At this time, MK-0646 is only being used in research. Gemcitabine is FDA approved and commercially available for the treatment of pancreatic cancer. Erlotinib hydrochloride is FDA approved and commercially available for the treatment of pancreatic cancer in combination with gemcitabine.
Up to 100 patients will take part in this study. All will be enrolled at MD Anderson.
Phase II Expansion Cohort:
The Study Drugs:
MK-0646 is designed to block proteins that are thought to cause cancer cells to grow and spread. This drug may help slow the growth of tumors.
Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells to die.
Study Treatments:
If you are found to be eligible to take part in this study, you will receive gemcitabine and MK-0646.
Study Drug Administration:
On Days 1, 8, and 15 of each 28-day study cycle, you will receive gemcitabine through a needle into your vein over about 1 1/2 hours as an infusion once a week for 3 weeks. On Days 1, 8, 15, and 22 of each cycle, you will receive MK-0646 by vein over 1 hour.
Depending upon how well you tolerate gemcitabine, your doctor may decide that you should receive gemcitabine on Days 1 and 15 instead of Days 1, 8, and 15.
Study Visits:
On Day 1 of Cycle 1, the following tests and procedures will be performed:
On Day 8 of Cycle 1, the following tests and procedures will be performed:
On Day 15 of Cycle 1, the following tests and procedures will be performed:
On Day 22 of Cycle 1, the following tests and procedures will be performed if you are receiving MK-0646:
On Day 1 of Cycles 2 and beyond, the following tests and procedures will be performed:
On Days 8 and 15 of Cycles 2 and beyond, the following tests and procedures will be performed:
On Day 22 of Cycles 2 and beyond, your vital signs and weight will be measured and you will be asked if you have experienced any side effects.
On Day 22 of Cycle 2 and every even cycle (Cycles 4, 6, 8, and so on), you will have a CT scan or MRI scan to check the status of the disease.
Length of Study:
You may remain on study for as long as you are benefiting. You will be taken off study 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:
Long-Term Follow Up:
Once you are off study, every 3 months from then on, the study staff will ask you how you are doing, either in the clinic or by telephone. If you are called, this phone call will take about 10-15 minutes.
This is an investigational study. MK-0646 is not FDA approved or commercially available. At this time, MK-0646 is only being used in research. Gemcitabine is FDA approved and commercially available for the treatment of pancreatic cancer.
Up to 100 patients total will take part in this study. All will be enrolled at MD Anderson.
Inclusion Criteria:
Exclusion Criteria: