Temsirolimus in Combination With Metformin in Patients With Advanced Cancers
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 14 - Any |
| Updated: | 1/12/2019 |
| Start Date: | March 26, 2012 |
| End Date: | March 2020 |
Phase I Study of Temsirolimus in Combination With Metformin in Patients With Advanced Cancers
Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential
participant.
The goal of this clinical research study is to find the highest tolerable dose of the
combination of temsirolimus and metformin that can be given to patients with advanced cancer.
The safety of the drug combination will also be studied.
Temsirolimus is designed to block a protein called mTOR (a protein that is thought to cause
cancer cells to grow) inside the cancer cell. This may interfere with the growth or spread of
cancer cells or possibly kill them.
Metformin was designed to treat patients with diabetes. It may be able to block the protein
mTOR and slow the growth of tumors.
This is an investigational study. Temsirolimus is FDA approved and commercially available for
the treatment of renal cell carcinoma. Metformin is FDA approved and commercially available
for the treatment of diabetes mellitus. The combination of these drugs to treat advanced
cancer is investigational.
Up to 104 patients will take part in this study. All will be enrolled at MD Anderson.
participant.
The goal of this clinical research study is to find the highest tolerable dose of the
combination of temsirolimus and metformin that can be given to patients with advanced cancer.
The safety of the drug combination will also be studied.
Temsirolimus is designed to block a protein called mTOR (a protein that is thought to cause
cancer cells to grow) inside the cancer cell. This may interfere with the growth or spread of
cancer cells or possibly kill them.
Metformin was designed to treat patients with diabetes. It may be able to block the protein
mTOR and slow the growth of tumors.
This is an investigational study. Temsirolimus is FDA approved and commercially available for
the treatment of renal cell carcinoma. Metformin is FDA approved and commercially available
for the treatment of diabetes mellitus. The combination of these drugs to treat advanced
cancer is investigational.
Up to 104 patients will take part in this study. All will be enrolled at MD Anderson.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose
level of temsirolimus and metformin based on when you join this study. Up to 6 dose levels of
temsirolimus and metformin will be tested. Up to 6 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 the combination of temsirolimus
and metformin is found.
Expansion Groups:
When the highest tolerable dose of the study drug combination is found, there will be one
group of up to 40 endometrial carcinoma patients enrolled in a tumor-specific expansion
group.
Study Drug Administration:
The first study cycle is 42 days and each cycle after that is 28 days. Before you start
taking both drugs in Cycle 1, you will take metformin only for the first 2 weeks. This is
called a titration period.
On Days 15, 22, 29 and 36 of Cycle 1, you will receive temsirolimus by vein over 30-60
minutes. For each cycle after that, you will receive temsirolimus by vein over 30-60 minutes
on Days 1, 8, 15, and 22.
Before you receive temsirolimus, you will receive Benadryl (diphenhydramine) by vein over
30-60 minutes to help lower the risk of allergic reactions.
You will take metformin by mouth every day at about the same time each day with a meal and
cup of water (about 8 ounces). You should take it at home except on the days when you have a
study visit. On study visit days, you may take the metformin before you receive the
temsirolimus. Depending on your dose, you may take metformin 1-3 times daily. Your study
doctor will tell you how to take this drug.
If you are taking metformin before you start this study, the study doctor will let you know
how often you will take the metformin and if you will skip the titration period visits
described below.
You will be given a letter to take to your home doctor(s) about your study drug
administration as part of your care provided outside of MD Anderson.
Study Visits:
At every study visit, you will be asked about your health, any other drugs you are taking,
and if you have had any side effects.
Exams and tests will be performed before you receive the study drugs that day. Cycle 1 Day 1
tests and exams may not have to be repeated if done within 7 days.
If you are part of the expansion group, within 7 days before Day 1 of Cycle 1:
- Blood (about 2 teaspoons) will be drawn for pharmacodynamic (PD) testing. PD testing
measures how the level of study drug in your body may affect the disease.
- If you are part of the expansion group and have a certain mutation, you will have a
biopsy for PD testing. The tumor biopsy will be collected using either a fine needle
aspiration or a core biopsy, depending on the location and size of the tumor. To perform
a core biopsy, a sample of tissue is removed using a hollow core needle that has a
cutting edge. To collect a fine needle aspirate, a small amount of tissue is withdrawn
through a needle. If you have questions about your mutation status, the doctor can
discuss this with you.
On Day 1 of Cycle 1 (titration period):
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 4 teaspoons) will be drawn for routine tests. You will be asked to not eat
anything for 8 hours before your blood draw.
- During Week 1 only, urine will be collected for routine tests.
On Day 8 of Cycle 1 (titration period), blood (about 2 teaspoons) will be drawn for routine
tests.
On Day 15 and Day 29 of Cycle 1:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- During Week 1 only, urine will be collected for routine tests.
On Day 22 and Day 36 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.
If you are part of the expansion group, on Day 37 of Cycle 1:
- Blood (about 2 teaspoons) will be drawn for PD testing.
- If you are part of the expansion group and have a certain mutation, you will have a
biopsy for PD testing.
On Day 1 of Cycles 2 and beyond:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 4 teaspoons) and urine will be collected for routine tests. You will be
asked to not eat anything for 8 hours before your blood draw.
On Day 15 of Cycles 2 and beyond, blood (about 2 teaspoons) will be drawn for routine tests.
About every 8 weeks, you will have an x-ray, CT scan, MRI scan, and/or PET/CT scan to check
the status of the disease. If the study doctor thinks it is needed, they will be performed
more often.
After about 6 months (about 6 cycles) of taking the study drugs, you will have the CT scan or
MRI scan every 2-4 cycles if your study doctor thinks it is needed.
Length of Study Participation:
You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drug if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over when you have completed the end-of-study visit.
End-of-Study Visit:
Within 30 days after your last dose of study drugs, you will return to the clinic. The
following tests and procedures will be performed:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 2 teaspoons) and urine will be collected for routine tests.
If you are part of the expansion group:
- Blood (about 2 teaspoons) will be drawn for PD testing if the disease gets worse.
- If you are part of the expansion group and have a certain mutation, you will have a
biopsy for PD testing if the disease gets worse.
If you are found to be eligible to take part in this study, you will be assigned to a dose
level of temsirolimus and metformin based on when you join this study. Up to 6 dose levels of
temsirolimus and metformin will be tested. Up to 6 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 the combination of temsirolimus
and metformin is found.
Expansion Groups:
When the highest tolerable dose of the study drug combination is found, there will be one
group of up to 40 endometrial carcinoma patients enrolled in a tumor-specific expansion
group.
Study Drug Administration:
The first study cycle is 42 days and each cycle after that is 28 days. Before you start
taking both drugs in Cycle 1, you will take metformin only for the first 2 weeks. This is
called a titration period.
On Days 15, 22, 29 and 36 of Cycle 1, you will receive temsirolimus by vein over 30-60
minutes. For each cycle after that, you will receive temsirolimus by vein over 30-60 minutes
on Days 1, 8, 15, and 22.
Before you receive temsirolimus, you will receive Benadryl (diphenhydramine) by vein over
30-60 minutes to help lower the risk of allergic reactions.
You will take metformin by mouth every day at about the same time each day with a meal and
cup of water (about 8 ounces). You should take it at home except on the days when you have a
study visit. On study visit days, you may take the metformin before you receive the
temsirolimus. Depending on your dose, you may take metformin 1-3 times daily. Your study
doctor will tell you how to take this drug.
If you are taking metformin before you start this study, the study doctor will let you know
how often you will take the metformin and if you will skip the titration period visits
described below.
You will be given a letter to take to your home doctor(s) about your study drug
administration as part of your care provided outside of MD Anderson.
Study Visits:
At every study visit, you will be asked about your health, any other drugs you are taking,
and if you have had any side effects.
Exams and tests will be performed before you receive the study drugs that day. Cycle 1 Day 1
tests and exams may not have to be repeated if done within 7 days.
If you are part of the expansion group, within 7 days before Day 1 of Cycle 1:
- Blood (about 2 teaspoons) will be drawn for pharmacodynamic (PD) testing. PD testing
measures how the level of study drug in your body may affect the disease.
- If you are part of the expansion group and have a certain mutation, you will have a
biopsy for PD testing. The tumor biopsy will be collected using either a fine needle
aspiration or a core biopsy, depending on the location and size of the tumor. To perform
a core biopsy, a sample of tissue is removed using a hollow core needle that has a
cutting edge. To collect a fine needle aspirate, a small amount of tissue is withdrawn
through a needle. If you have questions about your mutation status, the doctor can
discuss this with you.
On Day 1 of Cycle 1 (titration period):
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 4 teaspoons) will be drawn for routine tests. You will be asked to not eat
anything for 8 hours before your blood draw.
- During Week 1 only, urine will be collected for routine tests.
On Day 8 of Cycle 1 (titration period), blood (about 2 teaspoons) will be drawn for routine
tests.
On Day 15 and Day 29 of Cycle 1:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- During Week 1 only, urine will be collected for routine tests.
On Day 22 and Day 36 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.
If you are part of the expansion group, on Day 37 of Cycle 1:
- Blood (about 2 teaspoons) will be drawn for PD testing.
- If you are part of the expansion group and have a certain mutation, you will have a
biopsy for PD testing.
On Day 1 of Cycles 2 and beyond:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 4 teaspoons) and urine will be collected for routine tests. You will be
asked to not eat anything for 8 hours before your blood draw.
On Day 15 of Cycles 2 and beyond, blood (about 2 teaspoons) will be drawn for routine tests.
About every 8 weeks, you will have an x-ray, CT scan, MRI scan, and/or PET/CT scan to check
the status of the disease. If the study doctor thinks it is needed, they will be performed
more often.
After about 6 months (about 6 cycles) of taking the study drugs, you will have the CT scan or
MRI scan every 2-4 cycles if your study doctor thinks it is needed.
Length of Study Participation:
You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drug if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over when you have completed the end-of-study visit.
End-of-Study Visit:
Within 30 days after your last dose of study drugs, you will return to the clinic. The
following tests and procedures will be performed:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 2 teaspoons) and urine will be collected for routine tests.
If you are part of the expansion group:
- Blood (about 2 teaspoons) will be drawn for PD testing if the disease gets worse.
- If you are part of the expansion group and have a certain mutation, you will have a
biopsy for PD testing if the disease gets worse.
Inclusion Criteria:
1. Patients with advanced or metastatic cancer that is refractory to standard therapies,
who have relapsed after standard therapy, or whose cancers have no standard therapy
that induces a complete response (CR) rate of at least 10% or improves survival by at
least three months.
2. Patients must have evaluable or measurable disease by RECIST criteria.
3. Patients must be >/= 4 weeks beyond treatment of any chemotherapy, other
investigational therapy, hormonal, biological, targeted agents or radiotherapy, and
must have recovered to Patients may have received palliative low dose radiotherapy to the limbs 1-4 weeks
before this therapy provided pelvis, sternum, scapulae, vertebrae, or skull were not
included in the radiotherapy field. Patients who have received non-chemotherapeutic
biological agents will need to wait at least 5 half-lives or 4 wks, whichever is
shorter, from the last day of treatment. Continuation of hormone replacement therapy
is permitted. Stable regimens of hormonal therapy i.e. for prostate cancer (e.g.
leuprolide, a GnRH agonist), ovarian, or breast cancer are not exclusionary.
4. ECOG performance status
5. Abnormal organ function is permitted. However, patients must have absolute neutrophil
count >/= 1000/mL; platelets >/= 75,000/mL; creatinine < 1.5 mg/dl in males and < 1.4
in females;T. Bilirubin (SGPT)
6. Women of child-bearing potential MUST have a negative serum or urine pregnancy test
unless prior hysterectomy or menopause (defined as 12 consecutive months without
menstrual activity). Patients should not become pregnant or breastfeed while on this
study. Sexually active patients must agree to use contraception prior to study entry,
for the duration of study participation, and for 30 days after the last dose
7. Ability to understand and willingness to sign a written informed consent document.
8. Patients must be >/= 14 years of age.
9. Patients in the tumor-specific endometrial carcinoma expansion cohort that have known
mutation must be willing to provide consent for biopsies.
Exclusion Criteria:
1. Patients who are pregnant or breastfeeding.
2. Uncontrolled intercurrent illness including, but not limited to, active infection
requiring hospitalization.
3. History of hypersensitivity to temsirolimus or metformin.
4. History of CVA, myocardial infarction or unstable angina within the previous six
months before starting therapy
5. New York Heart Association Class III or greater congestive heart failure.
6. Patients with major surgery within 30 days prior to entering the study.
7. Patients unable to swallow oral medications or with pre-existing gastrointestinal
disorders that might interfere with proper absorption of oral drugs.
8. Patients on drugs that are strong P450 CYP3A4 modifiers. These drugs should be stopped
5 half-lives prior to starting investigational agents with temsirolimus. The strong
inducing or inhibiting agents should not restart until 1 week after the end of the
study treatment. NOTE: We will allow replacement of steroids (with either prednisone
or hydrocortisone) in patients with adrenalectomy.
9. Patients with a history of any grade of persistent or chronic nausea or vomiting
within the last 4 weeks related to prior therapy or disease process.
We found this trial at
1
site
1515 Holcombe Blvd
Houston, Texas 77030
Houston, Texas 77030
713-792-2121
University of Texas M.D. Anderson Cancer Center The mission of The University of Texas MD...
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