Imatinib Mesylate in Treating Patients With Recurrent or Persistent Uterine Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00075400
First received: January 9, 2004
Last updated: March 28, 2014
Last verified: March 2014
  Purpose

This phase II clinical trial studies the side effects and how well imatinib mesylate works in treating patients with uterine cancer that has failed to respond to initial chemotherapy or has re-grown after therapy. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Recurrent Uterine Sarcoma
Uterine Carcinosarcoma
Drug: imatinib mesylate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of Gleevec(TM) (NCI-Supplied Agent: STI571 [Imatinib Mesylate], NSC# 716051) in the Treatment of Recurrent or Persistent Carcinosarcoma of the Uterus

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: From study entry until disease progression, death or date of last contact, assessed at 6 months ] [ Designated as safety issue: No ]
  • Incidence of adverse effects as assessed by CTCAE v 3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    The frequency and severity of all toxicities are tabulated from submitted case report forms and summarized for review.


Secondary Outcome Measures:
  • Duration of PFS [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Duration of overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Clinical response (partial and complete response) as defined by RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Initial performance status [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Assessed as a prognostic factor.

  • Initial histologic grade [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Assessed as a prognostic factor.

  • c-KIT expression levels in archived, formalin-fixed, paraffin-embedded primary tumor tissue by immunohistochemistry (IHC) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Potential associations with clinical or PFS response will be assessed.

  • PDGFR expression levels in archived, formalin-fixed, paraffin-embedded primary tumor tissue by IHC [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Potential associations with clinical or PFS response will be assessed.

  • AKT2 expression levels in archived, formalin-fixed, paraffin-embedded primary tumor tissue by IHC [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Potential associations with clinical or PFS response will be assessed.

  • p-AKT2 expression levels in archived, formalin-fixed, paraffin-embedded primary tumor tissue [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Potential associations with clinical or PFS response will be assessed.


Enrollment: 51
Study Start Date: January 2004
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (imatinib mesylate)
Patients receive imatinib mesylate PO QD or BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: imatinib mesylate
Given PO
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the activity of Gleevec^trademark (TM) (imatinib mesylate) as measured by progression-free survival at six months.

II. To determine the frequency and severity of adverse effects of Gleevec^TM in this cohort of patients as assessed by the Common Terminology Criteria of Adverse Events version 3.0 (CTCAE v3.0).

SECONDARY OBJECTIVES:

I. To determine the distribution of progression-free survival and overall survival.

II. To estimate the objective response rate (partial and complete response as defined under the Response Evaluation Criteria In Solid Tumors [RECIST] criteria).

III. To determine the effects of prognostic factors such as initial performance status and histological grade.

TERTIARY OBJECTIVES:

I. To determine the levels of expression of v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (c-KIT), platelet-derived growth factor receptor (PDGFR), v-akt murine thymoma viral oncogene homolog 2 (AKT2), and phosphorylated (p)-AKT2 in archived, formalin-fixed, paraffin-embedded primary tumors collected prior to the initiation of first-line chemotherapy

OUTLINE:

Patients receive imatinib mesylate orally (PO) once daily (QD) or twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically confirmed uterine carcinosarcoma that is persistent or recurrent with documented disease progression after appropriate local therapy; acceptable histologic type is defined as carcinosarcoma (malignant mixed Mullerian tumor), homologous or heterologous type
  • All patients must have measurable disease; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or >= 10 mm when measured by spiral CT
  • Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST; tumors within a previously irradiated field will be designated as "non-target" lesions
  • Patients must not be eligible for a higher priority Gynecological Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG phase III protocol for the same patient population
  • Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2; patients who have received two prior regimens must have a GOG performance status of 0 or 1
  • Recovery from effects of recent surgery, radiotherapy, or chemotherapy

    • Patients should be free of active infection requiring antibiotics
    • Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration; continuation of hormone replacement therapy is permitted
    • Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to registration
  • Patients must have had one prior chemotherapeutic regimen for management of carcinosarcoma; initial treatment may include high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment
  • Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease according to the following definition:

    • Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa
    • Note: Patients on this non-cytotoxic study are allowed to receive one additional cytotoxic chemotherapy regimen for management of recurrent or persistent disease, as defined above; however, due to the novel nature of biologic compounds, patients are encouraged to enroll on second-line non-cytotoxic studies prior to receiving additional cytotoxic therapy
  • Patients must have NOT received any non-cytotoxic chemotherapy for management of recurrent or persistent disease
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to CTCAE v3.0 grade 1
  • Platelets greater than or equal to 100,000/mcl
  • Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE v3.0 grade 1
  • Bilirubin less than or equal to 1.5 x ULN (CTCAE v3.0 grade 1)
  • Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)
  • Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)
  • Neuropathy (sensory and motor) less than or equal to CTCAE v3.0 grade 1
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information
  • Patients who have met the pre-entry requirements
  • Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception, and cannot be lactating; since interactions with the metabolism of oral contraceptives cannot be excluded, a barrier method of contraception must be used
  • Patients must have tissue blocks from initial diagnosis available for submission to the GOG Tissue Bank

Exclusion Criteria:

  • Patients who had previous treatment with Gleevec^TM
  • Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer present within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy
  • Patients with signs or symptoms of bowel dysfunction or obstruction
  • Patients receiving therapeutic anticoagulation with warfarin
  • Patients with deep venous or arterial thrombosis (including pulmonary embolism) within six weeks of study entry
  • Patients receiving therapeutic corticosteroids
  • Patients with active or uncontrolled infection
  • History of seizures or those patients receiving phenytoin, phenobarbital, or carbamazepine
  • Patients with other severe concurrent disease, which the investigator feels may make the patients inappropriate for study entry
  • Presence of clinically apparent central nervous system metastases, or other carcinomatous meningitis
  • History of myocardial infarction within previous six months or congestive heart failure requiring therapy
  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: NCT00075400

Locations
United States, Pennsylvania
Gynecologic Oncology Group
Philadelphia, Pennsylvania, United States, 19103
Sponsors and Collaborators
Investigators
Principal Investigator: Warner Huh Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00075400     History of Changes
Other Study ID Numbers: NCI-2014-00653, NCI-2014-00653, CDR0000346361, GOG-0230C, GOG-0230C, U10CA027469
Study First Received: January 9, 2004
Last Updated: March 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinosarcoma
Mixed Tumor, Mullerian
Uterine Neoplasms
Sarcoma
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective and Soft Tissue
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014