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Uterine CancerPhase 1/2NCT00506779

Gleevec/Taxol for Patients With Uterine Papillary Serous Carcinoma

A Phase 1/2 study testing Imatinib Mesylate and Paclitaxel in people with Uterine Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Any age, women only
Conditions the study is for
Uterine Cancer
What is being tested?
Imatinib Mesylate and Paclitaxel
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
29 Dec 2003to Apr 2015
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
  • Patients may not receive concurrent radiotherapy while participating in this protocol.
  • Patients may have measurable or non-measurable disease.
  • Patients may have mixed endometrioid or clear cell components in addition to the serous histology.
  • 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.
  • 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.
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  • Patients must have an adequate renal function as documented by serum creatinine of </=2.0 mg/dl.
  • 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.
  • Zubrod performance status of 0, 1, or 2.
  • Patients should not have received prior chemotherapy or radiation (except palliative radiation) within the last 30 days.
  • Patients must have signed informed consent indicating that they are aware of the investigational nature of this study.

Who cannot join

  • Patients who have previously received imatinib mesylate or taxanes.
  • Patients with any active or uncontrolled systemic infection, including known HIV infection.
  • Patients with psychiatric disorders that would interfere with consent or follow-up.
  • Patients with New York Heart Association (NYHA) Class III/IV congestive heart failure, unstable angina or a history of myocardial infarction within the previous 6 months.
  • 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.
  • Oxygen-dependent lung disease.
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  • Patients in whom corticosteroids are contraindicated.
  • Uncontrolled severe hypertension or uncontrolled diabetes mellitus.
  • Presence of clinically apparent central nervous system metastases or carcinomatous meningitis.
  • Patients with any form of chronic liver disease.
  • Patients with a history of seizures are ineligible. Patients receiving phenytoin, phenobarbital, or other anti-epileptic prophylaxis are ineligible.
  • 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.
  • Patients with a deep venous or arterial thrombosis (including pulmonary embolism) within 6 weeks of study entry.
  • Patients who are receiving therapeutic doses of warfarin or any blood thinning agent.
  • Patients with a history of non-compliance with medical regimens or who are considered potentially unreliable.
  • Pregnant or lactating women. Women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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)

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.
Read the 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.

Conditions
Uterine Cancer
Being tested
Imatinib Mesylate, Paclitaxel
Keywords
Uterine Papillary Serous Carcinoma, Uterine Cancer, UPSC, Taxol, Paclitaxel, Gleevec, Imatinib Mesylate, STI571
Medical subject headings
Uterine Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Imatinib MesylateDrug

    Also called Gleevec, STI571, Imatinib, NSC-716051

    Phase I = Maximum tolerated dose (MTD) derived from dose escalation of 400, 500, 600 mg by mouth daily

  • PaclitaxelDrug

    Also called Taxol

    175 mg/m^2 by vein over 3 Hours every 21 Days

Study groups in NCT00506779
Study groupRoleWhat they receive
Phase I: Paclitaxel + Imatinib MesylateExperimentalPhase I MTD using oral dose Imatinib Mesylate escalation 400, 500, 600 mg daily; Paclitaxel 175 mg/m^2 every 21 days
Receives: Drug: Imatinib Mesylate; Drug: Paclitaxel
Phase II: Paclitaxel Alone or Pacliataxel + Imatinib MesylateExperimentalIntended randomization of Paclitaxel alone or Paclitaxel + Imatinib Mesylate; the study was terminated early due to poor enrollment and all patients are no longer being treated or followed. Single treatment arm MTD using oral dose Imatinib Mesylate escalation = 500 mg daily; Paclitaxel 175 mg/m^2 every 21 days Phase II, (Arm 1) = Paclitaxel 175 mg/m^2 every 21 days Phase II, (Arm 2) Paclitaxel 175 mg/m^2 every 21 days+ Imatinib Mesylate MTD using oral dose Imatinib Mesylate escalation = 500 mg daily
Receives: Drug: Imatinib Mesylate; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)

    Maximum Tolerated Dose (MTD) of Oral Imatinib Mesylate in Combination with Fixed Dose Paclitaxel where MTD of Imatinib Mesylate (mg/m^2 daily) to be determined with conventional 3+3 design, MTD is highest dose level in which 6 participants treated with at most 2 experiencing dose limiting toxicity (DLT). Study utilizes Common Terminology for Adverse Events Criteria (CTCAE) version 3.0 for adverse event reporting.

    Following cohorts of 3 at lower dose levels until 1 of 3 patients experiences DLT; if 1 of 3 patients experiences DLT at dose level, enter 3 additional patients at dose level, if only 1 of 6 patients experiences DLT at dose level, proceed to next higher dose level with cohort of 3; If 2 of 3 or 3 of 6 patients experience DLT, MTD has exceeded. Once DLT exceeded, treat another 3 patients at previous dose if there were only 3 patients treated at that dose level. MTD is highest dose level in which treated 6 patients with at most 2 experiencing the DLT.

    Measured: Evaluated at 3 weeks (one cycle)

Secondary outcomes (2)

  1. Number of Participants With Complete Response

    Complete Response (CR): Disappearance lesions, no evidence new lesions documented by 2 disease assessments> 4 weeks apart. Partial Response (PR):>30% decrease in sum longest dimensions (LD) all target measurable lesions reference baseline sum of LD; No progression non-target lesions \& no new lesions; Documentation by 2 disease assessments >4 weeks apart; Progressive Disease (PD) (ANY of following): >20% increase in sum LD of target lesions reference smallest sum LD or appearance of new lesions within 8 weeks of study entry; Unequivocal progression on existing non-target lesions, other than pleural effusions without cytological proof of neoplastic origin, within 8 weeks of study entry also considered increasing disease. Death due to disease without prior objective documentation of progression; Global deterioration in health attributable to disease requiring change in therapy without objective evidence of progression. Stable disease: Any condition not meeting above criteria.

    Measured: 6 weeks to 18 weeks; Best response achieved since study entry where measurable disease defined as => 1 lesion accurately measured in at least 1 dimension (longest dimension to be recorded)

  2. Time to Tumor Progression

    Efficacy of Gleevec and Taxol in Participants defined by tumor progression for participants with measurable disease or recurrent non-measurable disease. Time to tumor progression defined as the time from date of initial treatment to first objective documentation of disease progression. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). After two cycles (6 weeks), participants will undergo clinical and radiographic (participants with measurable disease) tumor restaging or confirmation recurrent non-measurable disease. Evaluation of tumor response (for participants who already have the disease) determined by CT scan or MRI and chest x-ray (participants with chest disease).

    Measured: Evaluation at at 6 weeks, tumor restaging continued up to 6 cycles (18 weeks) or until disease progression, whichever comes first

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jul 2007 (estimated)
  2. Study start29 Dec 2003
  3. Primary completionApr 2015
  4. Study completionApr 2015

Why it stopped: the study was terminated early due to poor enrollment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00506779
Sponsor's protocol ID
GYN03-0177
Other IDs
NCI-2012-01549
Status last verified
Oct 2020
First submitted
23 Jul 2007
Last updated
18 Nov 2020
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Imatinib Mesylate and Paclitaxel in people with Uterine Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) (time frame: Evaluated at 3 weeks (one cycle)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00506779.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2020.

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