Gleevec/Taxol for Patients With Uterine Papillary Serous Carcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00506779
First received: July 23, 2007
Last updated: September 29, 2014
Last verified: September 2014
  Purpose

Objectives:

  • To determine the maximum tolerated dose (MTD) of imatinib mesylate in combination with fixed dose paclitaxel in patients with stage IIIC, IV or recurrent uterine papillary serous carcinoma.
  • To determine the nature and degree of toxicity of imatinib mesylate and paclitaxel in this cohort of patients.
  • To determine the efficacy of imatinib mesylate and paclitaxel in patients with stage IIIC, IV or recurrent uterine papillary serous carcinoma whose tumor expresses either c-Kit, PDGFR or abl.

Condition Intervention Phase
Uterine Cancer
Drug: Imatinib Mesylate
Drug: Paclitaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of imatinib mesylate in combination with fixed dose paclitaxel [ Time Frame: Evaulated with each 3 week cycle ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 65
Study Start Date: December 2003
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paclitaxel + Imatinib Mesylate
Phase I, Phase II (Arm 2) = Paclitaxel + Imatinib Mesylate
Drug: Imatinib Mesylate

Phase I = 400 mg by mouth daily

Phase II (Arm 2) = 400 mg by mouth daily

Other Names:
  • Gleevec
  • STI571
  • Imatinib
  • NSC-716051
Drug: Paclitaxel
175 mg/m^2 by vein Over 3 Hours Every 21 Days
Other Name: Taxol
Experimental: 2
Phase II, (Arm 1) = Paclitaxel
Drug: Paclitaxel
175 mg/m^2 by vein Over 3 Hours Every 21 Days
Other Name: Taxol

  Hide Detailed Description

Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 </=2.0 mg/dl.
  8. Patients must have adequate hepatic function as documented by a serum bilirubin </=1.5mg/dl, regardless of whether patients have liver involvement secondary to tumor. Alanine aminotransferase (SGPT) and aspartate aminotransferase (SGOT) must be </=2.5x institutional upper limit of normal unless the liver is involved with tumor, in which case levels must be </=5x institutional upper limit of normal.
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00506779

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: David M. Gershenson, MD,BA M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00506779     History of Changes
Other Study ID Numbers: GYN03-0177
Study First Received: July 23, 2007
Last Updated: September 29, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Uterine Papillary Serous Carcinoma
Uterine Cancer
UPSC
Taxol
Paclitaxel
Gleevec
Imatinib Mesylate
STI571

Additional relevant MeSH terms:
Carcinoma
Cystadenocarcinoma, Serous
Uterine Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Cystadenocarcinoma
Adenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Paclitaxel
Imatinib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014