Gleevec/Taxol for Patients With Uterine Papillary Serous Carcinoma

NCT00506779 | Terminated Phase 1 Results

• 2 other identifiers: GYN03-0177NCI-2012-01549
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Uterine Cancer

Keywords

Uterine Papillary Serous Carcinoma; Uterine Cancer; UPSC; Taxol; Paclitaxel; Gleevec; Imatinib Mesylate; STI571

Outcome Measures

Primary Outcomes (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.

  Evaluated at 3 weeks (one cycle)

Secondary Outcomes (2)

• Number of Participants With Complete Response

  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)

• Time to Tumor Progression

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

Study Arms (2)

Phase I: Paclitaxel + Imatinib Mesylate

EXPERIMENTAL

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; Drug: Paclitaxel

Phase II: Paclitaxel Alone or Pacliataxel + Imatinib Mesylate

EXPERIMENTAL

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; Drug: Paclitaxel

Interventions

Imatinib Mesylate DRUG

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

Also known as: Gleevec, STI571, Imatinib, NSC-716051

Phase I: Paclitaxel + Imatinib Mesylate; Phase II: Paclitaxel Alone or Pacliataxel + Imatinib Mesylate

Paclitaxel DRUG

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

Also known as: Taxol

Phase I: Paclitaxel + Imatinib Mesylate; Phase II: Paclitaxel Alone or Pacliataxel + Imatinib Mesylate

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• The University of Texas M.D.Anderson Cancer Center

MeSH Terms

Conditions

Uterine Neoplasms

Interventions

Imatinib Mesylate; Paclitaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Results Point of Contact

• Title: David Gershenson, MD
• Organization: University of Texas (UT) MD Anderson Cancer Center

DGershen@mdanderson.org

713-745-2565

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2007
• First Posted: July 25, 2007
• Study Start: December 29, 2003
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: November 18, 2020
• Results First Posted: November 18, 2020

Record last verified: 2020-10

Locations

US (1)