Clinical trial NCT00075400: Imatinib Mesylate in Treating Patients With Recurrent or Persistent Uterine Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Uterine Sarcoma
Uterine Carcinosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Gynecologic Oncology Group
First posted: 2004-01-12
Enrollment: 26
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Progression-free Survival (PFS) > 6 Months
timeFrame: For those patients whose disease can be evaluated by physical examination, progression was assessed prior to each 28-day cycle. CT scan or MRI if used to follow measurable disease every other cycle for the first 6 months.
measure: Incidence of Adverse Effects as Assessed by CTCAE v 3.0
timeFrame: Each cycle during treatment and 30 days after treatment ends.
Secondary outcomes:
measure: Tumor Response
timeFrame: CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; up to 5 years
measure: Overall Survival
timeFrame: From study entry to death or last contact, up to 5 years.
measure: Duration of Progression Free Survival
timeFrame: CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; up to 5 years
measure: Initial Performance Status
timeFrame: Baseline
measure: Initial Histologic Grade
timeFrame: Baseline
Other outcomes:
measure: PDGFR Expression Levels in Archived, Formalin-fixed, Paraffin-embedded Primary Tumor Tissue by IHC
timeFrame: Baseline
measure: AKT2 Expression Levels in Archived, Formalin-fixed, Paraffin-embedded Primary Tumor Tissue by IHC
timeFrame: Baseline
measure: p-AKT2 Expression Levels in Archived, Formalin-fixed, Paraffin-embedded Primary Tumor Tissue
timeFrame: Baseline
measure: c-KIT Expression Levels in Archived, Formalin-fixed, Paraffin-embedded Primary Tumor Tissue by Immunohistochemistry (IHC)
timeFrame: Baseline
Locations:
city: Philadelphia
country: United States
facility: Gynecologic Oncology Group
state: Pennsylvania
Study officials:
affiliation: Gynecologic Oncology Group
name: Warner Huh
role: PRINCIPAL_INVESTIGATOR
References: