A Phase I/II Study to Evaluate the Efficacy and Toxicity of Imatinib Mesylate in Combination With Dacarbazine and Capecitabine in Medullary Thyroid Carcinoma
16 Years
N/A
Both
Solid Tumor, Thyroid Cancer
Trial Information
A Phase I/II Study to Evaluate the Efficacy and Toxicity of Imatinib Mesylate in Combination With Dacarbazine and Capecitabine in Medullary Thyroid Carcinoma
Phase I:
Imatinib mesylate is a drug that binds to certain proteins on the tumor cells, which may
prevent the cells from growing. Capecitabine and dacarbazine are drugs that interfere with
the growth of cancer cells.
If you are found to be eligible to take part in this study, you will begin treatment with
imatinib mesylate, capecitabine, and dacarbazine.
You will come to M. D. Anderson at least once every three weeks (21 days) for treatment.
Each 21-day period of treatment is called a "cycle" of therapy. You will receive at least 3
cycles of therapy (9 weeks) unless side effects are severe or the cancer grows very quickly.
The first group of study participants will receive lower doses of imatinib mesylate,
capecitabine and dacarbazine. If these doses appear to be safe, the next group of
participants will receive higher doses. This will continue until the highest doses that may
be safely given are found.
You will take imatinib mesylate capsules by mouth once a day on Days 1-21 of each cycle.
Imatinib mesylate should be taken with a meal with a large glass of water.
You will take capecitabine tablets by mouth twice a day on Days 1-14 of each cycle. You
should take each dose of capecitabine within 30 minutes after eating a meal. It is
important to take the tablets together with water and not fruit juices. Each dose of
capecitabine should be about 12 hours apart (for example, after breakfast and after your
evening meal).
You will have a small tube (central venous line) inserted into a large vein under the skin
of the chest or through a vein in the arm to receive dacarbazine. Dacarbazine will be given
over 1 hour on Days 1-3 of each cycle.
During the first cycle of therapy, blood (about 2 ½ teaspoons) will be collected once a week
for routine tests. Before each new cycle of therapy, you will have a complete physical exam
and urine and blood (about 2 ½ teaspoons) will be collected for routine tests. You will be
asked to tell the study doctor about all medications you have taken since you started taking
the study drugs and any health problems that you may have experienced. You will also have
either CT scans or a MRI of the tumor(s) every 9 weeks and at the end of the study.
Additional tests may be done during the study if your doctor feels it is necessary for your
care. All tests before each new cycle of treatment and when treatment stops must be done
at M. D. Anderson.
You should always tell the study doctor if you are taking any other medication, if you have
seen another doctor, if you have received new treatments or if there is any change in the
way you are feeling since the last visit. If you are seeing another doctor(s), you should
inform these doctors that you are currently in this study. Have the doctor contact the
study doctor to discuss any other necessary treatments.
If you experience severe side effects, treatment may be delayed, stopped, or you may receive
smaller doses of the drugs. You may continue to receive treatment on this study until the
disease gets worse or you experience any intolerable side effects. If this happens, you
will be taken off the study and your doctor will discuss other treatment options with you.
When you stop taking part in the study, you will have blood (about 3 teaspoons) collected
for routine tests. You will have a physical exam and either a CT scan or a MRI to check on
the status of the disease. You will be contacted by phone every three months for the rest
of your life to check on the status of the disease and on any symptoms you may be
experiencing.
This is an investigational study. The drugs dacarbazine, imatinib mesylate, and
capecitabine are FDA approved and commercially available for treating certain forms of
cancer. Up to 24 participants will take part in this study. All will be enrolled at M. D.
Anderson.
Phase II:
Imatinib mesylate is a drug that binds to certain proteins on the tumor cells, which may
prevent the cells from growing. Capecitabine and dacarbazine are drugs that interfere with
the growth of cancer cells.
If you are found to be eligible to take part in this study, you will begin treatment with
imatinib mesylate, capecitabine, and dacarbazine.
You will come to M. D. Anderson at least once every three weeks (21 days) for treatment.
Each 21-day period of treatment is called a "cycle" of therapy. You will receive at least 3
cycles of therapy (9 weeks) unless side effects are severe or the cancer grows very quickly.
You will take imatinib mesylate capsules by mouth once a day on Days 1-21 of each cycle.
Imatinib mesylate should be taken with a meal with a large glass of water.
You will take capecitabine tablets by mouth twice a day on Days 1-14 of each cycle. You
should take each dose of capecitabine within 30 minutes after eating a meal. It is
important to take the tablets together with water and not fruit juices. Each dose of
capecitabine should be about 12 hours apart (for example, after breakfast and after your
evening meal)
You will have a small tube (central venous line) inserted into a large vein under the skin
of the chest or through a vein in the arm to receive dacarbazine. Dacarbazine will be given
over 1 hour on Days 1-3 of each cycle.
During the first cycle of therapy, blood (about 2 ½ teaspoons) will be collected once a week
for routine tests. Before each new cycle of therapy, you will have a complete physical exam
and urine and blood (about 2 ½ teaspoons) will be collected for routine tests. You will be
asked to tell the study doctor about all medications you have taken since you started taking
the study drugs and any health problems that you may have experienced. You will also have
either CT scans or a MRI of the tumor(s) every 9 weeks and at the end of the study.
Additional tests may be done during the study if your doctor feels it is necessary for your
care. All tests before each new cycle of treatment and when treatment stops must be done
at M. D. Anderson.
You should always tell the study doctor if you are taking any other medication, if you have
seen another doctor, if you have received new treatments or if there is any change in the
way you are feeling since the last visit. If you are seeing another doctor(s), you should
inform these doctors that you are currently in this study. Have the doctor contact the
study doctor to discuss any other necessary treatments.
If you experience severe side effects, treatment may be delayed, stopped, or you may receive
smaller doses of the drugs. You may continue to receive treatment on this study until the
disease gets worse or you experience any intolerable side effects. If this happens, you
will be taken off the study and your doctor will discuss other treatment options with you.
When you stop taking part in the study, you will have blood (about 3 teaspoons) collected
for routine tests. You will have a physical exam and either a CT scan or a MRI to check on
the status of the disease. You will be contacted by phone every three months for the rest
of your life to check on the status of the disease and on any symptoms you may be
experiencing.
This is an investigational study. The drugs dacarbazine, imatinib mesylate, and
capecitabine are FDA approved and commercially available for treating other forms of cancer.
They are not approved for the treatment of medullary thyroid carcinoma. Up to 28
participants will take part in this study. All will be enrolled at M. D. Anderson.
Inclusion Criteria:
1. Age greater than 16 years old.
2. Signed informed consent.
3. During the phase I portion of the trial, any patient with a proven solid tumor for
which no curative or standard treatment is available is eligible. However, for the
phase II portion of the trial, patients are required to have medullary thyroid
carcinoma that is unresectable or metastatic.
4. For the phase I portion of the protocol, there is no limit to the amount of prior
therapy participants may have received. For the phase II portion of the trial, 0-1
prior regimens are allowed.
5. ECOG performance status must be 0-2.
6. Adequate hepatic, renal, and bone marrow function: Absolute neutrophil count greater
than/equal to 1,500/uL; platelets greater than/equal to 100,000/uL; total bilirubin
less than/equal to 1.5 X institution upper limits of normal (ULN); AST (SGOT)/ALT
(SGPT) less than/equal to 2.5 X institutional ULN; Creatinine less than/equal to 1.5
mg/dL
7. Female patients of childbearing potential must have a negative pregnancy test within
7 days before initiation of study drug dosing. Postmenopausal women must be
amenorrheic for at least 12 months to be considered of non-childbearing potential.
Male and female patients of reproductive potential must agree to employ an effective
barrier method of birth control throughout the study and for up to 3 months following
discontinuation of study drug.
8. Patients may have received prior radiation treatment but the last fraction of
radiation treatment must have been completed at least 4 weeks prior to entry on this
study.
9. Patients may have been treated with surgery but the surgical intervention must have
been done at least 3 weeks prior to entry on this study.
10. In the phase I part of the trial, measurable disease is not required. Radiographic
and measurable evidence of disease is required for the phase II part of the trial. To
be considered evaluable for complete or partial response, patients must have at least
one measurable lesion as per the modified RECIST Criteria. If radiation was
previously received, measurable disease must occur outside the previous radiation
field, unless disease progression has been documented.
11. Both men and women and members of all ethnic groups are eligible for this trial.
Exclusion Criteria:
1. In previously treated patients, patients should not have received prior dacarbazine,
imatinib mesylate, 5-fluorouracil, or capecitabine. This requirement does not apply
to the phase I patients.
2. Uncontrolled intercurrent illness including, but not limited to, active infection,
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmias
not well controlled with medication, myocardial infarction within the previous 6
months, or psychiatric illness/social situations that would limit compliance with
study requirements.
3. Patients who have had chemotherapy within 3 weeks prior to entering the study or
those who have not recovered from adverse events due to agents administered more than
28 days earlier.
4. Patients may not be receiving any other investigational agents, or have participated
in any investigational drug study within 28 days preceding start of study treatment.
5. The teratogenic potential of this combination is currently unknown. Women who are
pregnant or lactating are excluded.
6. History of any other malignancy in the last 5 years, except that patients with a
prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
Patients with treated disease processes believed to be associated with MEN2, such as
pheochromocytomas and primary hyperparathyroidism are allowed in the study.
7. Concomitant use of warfarin is not allowed. Low molecular weight and standard heparin
use is allowed.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Phase I: To find what doses of the drugs Gleevec (imatinib mesylate), DTIC-Dome (dacarbazine) and Xeloda (capecitabine) may be given together safely.
Outcome Time Frame:
5 Years
Safety Issue:
Yes
Principal Investigator
James Yao, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
2004-0475
NCT ID:
NCT00354523
Start Date:
December 2004
Completion Date:
Related Keywords:
- Solid Tumor
- Thyroid Cancer
- Solid Tumor
- Thyroid Cancer
- Medullary Thyroid Cancer
- MTC
- Advanced Metastatic Medullary Thyroid Carcinoma
- Capecitabine
- Dacarbazine
- Imatinib
- Gleevec
- Imatinib Mesylate
- DTIC-Dome
- Xeloda
- Carcinoma
- Thyroid Neoplasms
- Thyroid Diseases
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
