A Phase 1/2 interventional study of MK-0646 and Gemcitabine in Pancreatic Cancer and Pancreatic Adenocarcinoma, sponsored by M.D. Anderson Cancer Center. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-09-03.
Sponsored by M.D. Anderson Cancer Center · Phase 1/2, Interventional, and Treatment
Objectives:
Primary Objectives:
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.
2,002 studies on the registry are indexed under Adenocarcinoma; 375 are open to participants now.
This study's enrollment of 81 is above the median of 45 across 1,551 interventional studies indexed under Adenocarcinoma.
Browse Adenocarcinoma studies →M.D. Anderson Cancer Center is the lead sponsor of 2,999 studies on the registry; 579 are open to participants now.
Of its 599 completed or terminated interventional studies of FDA-regulated products, 402 (67%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
MK-0646 + Gemcitabine
Drug: MK-0646 · Drug: Gemcitabine
MK-0646 + Gemcitabine + Erlotinib
Drug: MK-0646 · Drug: Gemcitabine · Drug: Erlotinib
Gemcitabine + Erlotinib
Drug: MK-0646 · Drug: Gemcitabine
MK-0646 + Gemcitabine + Erlotinib
Drug: MK-0646 · Drug: Gemcitabine · Drug: Erlotinib
Gemcitabine + Erlotinib
Drug: Gemcitabine · Drug: Erlotinib
Starting Dose Level: 5 mg/kg given intravenously over 60 minutes Days 1, 8, 15, 22 of 28 Day Cycle.
1000 mg/m\^2 given intravenously over 1-1/2 hours Days 1, 8, and 15 of each 28 Day Cycle.
Also known as: Gemzar, Gemcitabine Hydrochloride
100 mg by mouth daily.
Also known as: OSI-774, Tarceva, Erlotinib Hydrochloride
MK-0646 Maximum Tolerable Dose
MK-0646 10 mg/kg was declared to be the MTD in combination with gemcitabine and 5 mg/kg the MTD in combination with Gemcitabine and erlotinib
Time frame: up to 12 cycles
Progression Free Survival
Time interval (in months) from date of randomization until the date of first documented progression or date of death from any cause, whichever came first
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall Survival
Time interval (in months) from date of randomization until the date of death from any cause
Time frame: From date of randomization until the date of death from any cause, assessed up to 100 months
Overall Response Rate
Complete response + Partial response using RECIST (Response Evaluation Criteria in Solid Tumors)
Time frame: From start of the treatment until disease progression/recurrence; or through study completion (average of 1 year)
Treatment Toxicity
Number of patients who developed toxicity from treatment according to the National Cancer Institute's Common Terminology Criteria
Time frame: Through the treatment cycles
Correlation Between Tissue IGF-I Expression in Patients Treated With MK-0646 and OS
IGF1 expression in tissue was measured and correlated with 1 year patients survival. Inadequate biopsy data for outcome measure.
Time frame: After completing treatment
Correlation Between Plasma IGF-I Expression in Patients Treated With MK-0646 and OS
IGF1 expression in plasma was measured in patients and correlated with 1 year patients survival. Inadequate biopsy data for outcome measure.
Time frame: After completing treatment
Completed, last patient enrolled in September 26th, 2013
| Milestone | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion |
|---|---|---|---|---|---|---|
| Started | 9 | 13 | 15 | 15 | 16 | 9 |
| Completed | 9 | 12 | 15 | 15 | 15 | 9 |
| Not completed | 0 | 1 | 0 | 0 | 1 | 0 |
| Withdrew: Withdrawal by subject | 0 | 1 | 0 | 0 | 1 | 0 |
MK-0646 10 mg/kg was declared to be the MTD in combination with gemcitabine and 5 mg/kg the MTD in combination with Gemcitabine and erlotinib
| participants | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion |
|---|---|---|---|---|---|---|
| MK 5mg +G: #DLT | 0 | 0 | — | — | — | — |
| MK 10mg +G: # DLT | 0 | 2 | — | — | — | — |
Time interval (in months) from date of randomization until the date of first documented progression or date of death from any cause, whichever came first
| months | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion |
|---|---|---|---|---|---|---|
| Progression Free Survival | — | — | 1.8 (1.8 to 9.7) | 1.8 (1.7 to 5.5) | 1.9 (1.8 to 5.4) | 2.0 (1.8 to NA) |
Time interval (in months) from date of randomization until the date of death from any cause
| months | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion |
|---|---|---|---|---|---|---|
| Overall Survival | — | — | 10.4 (3.9 to 18.9) | 7.1 (5.2 to 20.0) | 5.7 (4.0 to 9.5) | 8.2 (5.3 to NA) |
Complete response + Partial response using RECIST (Response Evaluation Criteria in Solid Tumors)
| Participants | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion |
|---|---|---|---|---|---|---|
| Overall Response Rate | 0 | 0 | 2 | 1 | 2 | 0 |
Number of patients who developed toxicity from treatment according to the National Cancer Institute's Common Terminology Criteria
| Participants | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion |
|---|---|---|---|---|---|---|
| Treatment Toxicity | 9 | 12 | 15 | 15 | 15 | 9 |
IGF1 expression in tissue was measured and correlated with 1 year patients survival. Inadequate biopsy data for outcome measure.
Results for this outcome have not been posted.
IGF1 expression in plasma was measured in patients and correlated with 1 year patients survival. Inadequate biopsy data for outcome measure.
Results for this outcome have not been posted.
Collected over assessed up to 100 months. Non-serious events are listed at a 3.5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm A / Phase I | 9/9 (100%) | 0/9 (0%) | 9/9 (100%) |
| Arm B / Phase I | 12/12 (100%) | 2/12 (16.7%) | 12/12 (100%) |
| Arm A / Phase II Randomization | 15/15 (100%) | 2/15 (13.3%) | 15/15 (100%) |
| Arm B / Phase II Randomization | 15/15 (100%) | 4/15 (26.7%) | 15/15 (100%) |
| Arm C / Phase II Randomization | 15/15 (100%) | 1/15 (6.7%) | 12/15 (80%) |
| Phase II Expansion | 9/9 (100%) | 1/9 (11.1%) | 9/9 (100%) |
| Event | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion |
|---|---|---|---|---|---|---|
| G4 neutropenia for ≥7 daysBlood and lymphatic system disorders | 0/9 | 2/12 | 2/15 | 4/15 | 0/15 | 1/9 |
| G4 thrombocytopeniaBlood and lymphatic system disorders | 0/9 | 0/12 | 1/15 | 1/15 | 1/15 | 0/9 |
| Event | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion |
|---|---|---|---|---|---|---|
| LeukopeniaBlood and lymphatic system disorders | 9/9 | 10/12 | 6/15 | 4/15 | 5/15 | 0/9 |
| NeutropeniaBlood and lymphatic system disorders | 9/9 | 8/12 | 6/15 | 7/15 | 9/15 | 4/9 |
| ThrombocytopeniaBlood and lymphatic system disorders | 9/9 | 7/12 | 9/15 | 8/15 | 11/15 | 7/9 |
| FatigueGeneral disorders | 6/9 | 10/12 | 6/15 | 4/15 | 7/15 | 8/9 |
| AnemiaBlood and lymphatic system disorders | 7/9 | 5/12 | 7/15 | 4/15 | 9/15 | 1/9 |
| LymphopeniaBlood and lymphatic system disorders | 7/9 | 3/12 | 3/15 | 0/15 | 3/15 | 1/9 |
| HyperglycemiaEndocrine disorders | 7/9 | 6/12 | 8/15 | 5/15 | 2/15 | 2/9 |
| NauseaGastrointestinal disorders | 4/9 | 7/12 | 2/15 | 3/15 | 7/15 | 4/9 |
| Elevated ASTHepatobiliary disorders | 5/9 | 5/12 | 6/15 | 6/15 | 3/15 | 2/9 |
| Elevated ALTHepatobiliary disorders | 4/9 | 6/12 | 5/15 | 3/15 | 2/15 | 3/9 |
| Age, Categorical(Participants) | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion | Total |
|---|---|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 5 | 5 | 9 | 10 | 7 | 6 | 42 |
| >=65 years | 4 | 7 | 6 | 5 | 8 | 3 | 33 |
| Age, Continuous(years) | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion | Total |
|---|---|---|---|---|---|---|---|
| Mean | 63.56 ± 7.21 | 63.33 ± 12.57 | 62.33 ± 7.66 | 62.27 ± 7.62 | 67.8 ± 8.41 | 60.89 ± 9.43 | 63.5 ± 8.9 |
| Sex: Female, Male(Participants) | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion | Total |
|---|---|---|---|---|---|---|---|
| Female | 3 | 3 | 7 | 6 | 5 | 4 | 28 |
| Male | 6 | 9 | 8 | 9 | 10 | 5 | 47 |
| Ethnicity (NIH/OMB)(Participants) | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion | Total |
|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 1 | 0 | 0 | 3 | 0 | 4 |
| Not Hispanic or Latino | 9 | 11 | 15 | 14 | 12 | 8 | 69 |
| Unknown or Not Reported | 0 | 0 | 0 | 1 | 0 | 1 | 2 |
| Race (NIH/OMB)(Participants) | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion | Total |
|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 1 | 1 | 0 | 2 | 0 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 2 | 1 | 0 | 1 | 4 |
| White | 9 | 10 | 12 | 13 | 10 | 7 | 61 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 1 | 0 | 1 | 3 | 1 | 6 |
| Region of Enrollment(participants) | Arm A / Phase I | Arm B / Phase I | Arm A / Phase II Randomization | Arm B / Phase II Randomization | Arm C / Phase II Randomization | Phase II Expansion | Total |
|---|---|---|---|---|---|---|---|
| United States | 9 | 12 | 15 | 15 | 15 | 9 | 75 |
Documents are hosted by the registry — open the source record to download them.
This study is completed, as verified in Sep 2020. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
M.D. Anderson Cancer Center