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
Overview
- Phase
- Phase 2
- Intervention
- imatinib mesylate
- Conditions
- Recurrent Uterine Sarcoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Progression-free Survival (PFS) > 6 Months
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
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
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
Arms & Interventions
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.
Intervention: imatinib mesylate
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.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Progression-free Survival (PFS) > 6 Months
Time Frame: 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.
Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.
Incidence of Adverse Effects as Assessed by CTCAE v 3.0
Time Frame: Each cycle during treatment and 30 days after treatment ends.
The frequency and severity of all toxicities are tabulated from submitted case report forms and summarized for review.
Secondary Outcomes
- Overall Survival(From study entry to death or last contact, up to 5 years.)
- Tumor Response(CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; up to 5 years)
- Duration of Progression Free Survival(CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; up to 5 years)
- Initial Histologic Grade(Baseline)
- Initial Performance Status(Baseline)