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Gleevec/Taxol for Patients With Uterine Papillary Serous Carcinoma

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ClinicalTrials.gov Identifier: NCT00506779
Recruitment Status : Terminated (the study was terminated early due to poor enrollment)
First Posted : July 25, 2007
Results First Posted : November 18, 2020
Last Update Posted : November 18, 2020
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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.
  • 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 or disease Intervention/treatment Phase
Uterine Cancer Drug: Imatinib Mesylate Drug: Paclitaxel Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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)
Actual Study Start Date : December 29, 2003
Actual Primary Completion Date : April 2015
Actual Study Completion Date : April 2015


Arm Intervention/treatment
Experimental: Phase I: Paclitaxel + Imatinib Mesylate
Phase I MTD using oral dose Imatinib Mesylate escalation 400, 500, 600 mg daily; Paclitaxel 175 mg/m^2 every 21 days
Drug: Imatinib Mesylate
Phase I = Maximum tolerated dose (MTD) derived from dose escalation of 400, 500, 600 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: Phase II: Paclitaxel Alone or Pacliataxel + Imatinib Mesylate

Intended 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

Drug: Imatinib Mesylate
Phase I = Maximum tolerated dose (MTD) derived from dose escalation of 400, 500, 600 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




Primary Outcome Measures :
  1. Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) [ Time Frame: Evaluated at 3 weeks (one cycle) ]

    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.



Secondary Outcome Measures :
  1. Number of Participants With Complete Response [ Time Frame: 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) ]
    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.

  2. Time to Tumor Progression [ Time Frame: Evaluation at at 6 weeks, tumor restaging continued up to 6 cycles (18 weeks) or until disease progression, whichever comes first ]
    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).



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes 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 New York Heart Association (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00506779


Locations
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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00506779    
Other Study ID Numbers: GYN03-0177
NCI-2012-01549 ( Registry Identifier: NCI CTRP )
First Posted: July 25, 2007    Key Record Dates
Results First Posted: November 18, 2020
Last Update Posted: November 18, 2020
Last Verified: October 2020
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:
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Carcinoma
Uterine Neoplasms
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Cystadenocarcinoma
Adenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Paclitaxel
Imatinib Mesylate
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors