A Phase I/II Study of Gleevec/Taxol in Patients With Newly Diagnosed Stage IIIC or IV or Recurrent (Any Stage) Uterine Papillary Serous Carcinoma (UPSC)
N/A
N/A
Female
Uterine Cancer
Trial Information
A Phase I/II Study of Gleevec/Taxol in Patients With Newly Diagnosed Stage IIIC or IV or Recurrent (Any Stage) Uterine Papillary Serous Carcinoma (UPSC)
Before possible study participants can receive treatment with imatinib mesylate and
paclitaxel, their tumor tissue that was previously collected (at the surgery to diagnose
your tumor) will be tested for the following three biomarkers: c-Kit, PDGFR-B, and Abl.
Those participants who have at least one positive biomarker will be eligible for treatment
on this study.
Paclitaxel is a chemotherapy drug used in the treatment of ovarian cancer. Imatinib mesylate
is a medication that blocks several proteins that are important in the development of
cancer.
Before treatment starts, you will have a complete physical exam, routine blood tests (about
2-3 teaspoons), an electrocardiogram (ECG--a test to measure the electrical activity of the
heart). You will have an echocardiogram (an ultrasound test used to visualize the
structures of the heart), a chest x-ray, and a CT scan or MRI of the abdomen and pelvis.
Women who are able to have children must have a negative blood pregnancy test.
Routine blood tests (about 2 teaspoons) will be done weekly during treatment, and before
each course of therapy, which is every 3 weeks. A complete checkup including evaluation of
side effects, will also be done before each course of therapy and at the end of therapy (3
weeks after treatment ends).
There are two phases to this study, Phase I and Phase II. If you are assigned to Phase 1,
you will receive treatment with imatinib mesylate and paclitaxel. Phase 1 will study 3
different doses of imatinib mesylate in combination with a fixed dose of paclitaxel. The
Phase I part of the study will help researchers learn the most effective dose of imatinib
mesylate to be used in combination with paclitaxel. All participants in Phase 1 will
receive one of three doses of imatinib mesylate to be given with a standard dose of
paclitaxel. You will be assigned to a specific dose level based on the number of
participants treated at the time of your enrollment.
The Phase II portion of the study will begin only after the most effective dose of imatinib
mesylate has been determined.
If you are assigned to Phase II, you will be randomly assigned (as in the toss of a coin) to
one of two treatment groups. Participants in one group will receive treatment with
paclitaxel only (every 21 days). Participants in the second group will receive treatment
with paclitaxel (every 21 days) along with imatinib mesylate (every day). The dose level of
imatinib mesylate that you receive will be the same as the dose used during Phase I. The
computer-generated assignment will favor the treatment group which is more effective. For
example, if the combination of paclitaxel and imatinib mesylate is more effective than
paclitaxel alone, then more patients will be selected to receive the combination therapy.
You will receive paclitaxel by vein over 3 hours every 21 days. Those participants who are
assigned treatment with both paclitaxel and imatinib mesylate will begin taking imatinib
mesylate the day after the first dose of paclitaxel. A single dose of imatinib mesylate
will be taken by mouth every day.
Evaluation of tumor response (for participants who already have the disease) will be
determined by CT scan or MRI and chest x-ray (patients with chest disease). These scans
will be taken after Courses 2 and 4 , then after every 3 courses until the therapy is
finished, and once more at the end of therapy. Patients who show no signs of the disease
will be given a total of up to 6 courses. Patients who have the disease may continue
treatment until the disease gets worse. You will be taken off study if the disease gets
worse or intolerable side effects occur. If you are removed from the study, you will be
asked to have a follow-up CT scan or MRI and chest x-ray to evaluate the tumor.
THIS IS AN INVESTIGATIONAL STUDY. Paclitaxel is commercially available and approved for use
in the treatment of ovarian cancer. Gleevec® is also commercially available and approved
for use in the treatment of certain types of adult leukemias and stomach cancers. The
combination of paclitaxel and imatinib mesylate is still investigational and has been
approved for use in research only.
At least 51 and as many as 65 participants will take part in this study. All participants
will be enrolled and treated at M. D. Anderson.
Inclusion Criteria:
1. Histologically confirmed newly diagnosed (stage IIIC or IV) or recurrent (any stage)
uterine papillary serous carcinoma. Patients with recurrent disease may not have been
treated with taxanes in the past.
2. Patients may not receive concurrent radiotherapy while participating in this
protocol.
3. Patients may have measurable or non-measurable disease.
4. Patients may have mixed endometrioid or clear cell components in addition to the
serous histology.
5. Patients' tumor tissue must express one or more of the following biomarkers: c-Kit,
PDGFR-B, or Abl. Positivity will be defined as 2+/3+ intensity in at least 10% of the
tumor.
6. Patients must have pretreatment granulocyte count (i.e. segmented neutrophils and
bands) of >/= 1,500/Fl, a hemoglobin level of >/= 9.0 gm/dl, and a platelet count of
>/= 100,000/Fl.
7. Patients must have an adequate renal function as documented by serum creatinine of
8. Patients must have adequate hepatic function as documented by a serum bilirubin
tumor. Alanine aminotransferase (SGPT) and aspartate aminotransferase (SGOT) must be
in which case levels must be
9. Zubrod performance status of 0, 1, or 2.
10. Patients should not have received prior chemotherapy or radiation (except palliative
radiation) within the last 30 days.
11. Patients must have signed informed consent indicating that they are aware of the
investigational nature of this study.
Exclusion Criteria:
1. Patients who have previously received imatinib mesylate or taxanes.
2. Patients with any active or uncontrolled systemic infection, including known HIV
infection.
3. Patients with psychiatric disorders that would interfere with consent or follow-up.
4. Patients with NYHA Class III/IV congestive heart failure, unstable angina or a
history of myocardial infarction within the previous 6 months.
5. Patients with a history of prior malignancy except for adequately treated basal cell
or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the
patient has been disease-free for at least three years.
6. Oxygen-dependent lung disease.
7. Patients in whom corticosteroids are contraindicated.
8. Uncontrolled severe hypertension or uncontrolled diabetes mellitus.
9. Presence of clinically apparent central nervous system metastases or carcinomatous
meningitis.
10. Patients with any form of chronic liver disease.
11. Patients with a history of seizures are ineligible. Patients receiving phenytoin,
phenobarbital, or other anti-epileptic prophylaxis are ineligible.
12. Patients with any other severe concurrent disease, which in the judgment of the
investigator, would make the patient inappropriate for entry into this study,
including significant hepatic, renal, or gastrointestinal diseases.
13. Patients with a deep venous or arterial thrombosis (including pulmonary embolism)
within 6 weeks of study entry.
14. Patients who are receiving therapeutic doses of warfarin or any blood thinning agent.
15. Patients with a history of non-compliance with medical regimens or who are considered
potentially unreliable.
16. Pregnant or lactating women. Women of reproductive potential may not participate
unless they have agreed to use an effective contraceptive method.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose (MTD) of imatinib mesylate in combination with fixed dose paclitaxel
Outcome Time Frame:
Evaulated with each 3 week cycle
Safety Issue:
Yes
Principal Investigator
David M. Gershenson, MD,BA
Investigator Role:
Principal Investigator
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
GYN03-0177
NCT ID:
NCT00506779
Start Date:
December 2003
Completion Date:
Related Keywords:
- Uterine Cancer
- Uterine Papillary Serous Carcinoma
- Uterine Cancer
- UPSC
- Taxol
- Paclitaxel
- Gleevec
- Imatinib Mesylate
- STI571
- Carcinoma
- Uterine Neoplasms
- Cystadenocarcinoma, Serous
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
