Selumetinib in Treating Patients With Recurrent or Persistent Endometrial Cancer
Condition: Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Recurrent Uterine Corpus Carcinoma
MeSH terms: Carcinoma; Adenocarcinoma; Adenocarcinoma, Clear Cell; Carcinoma, Adenosquamous; Recurrence
Intervention: Diagnostic Laboratory Biomarker Analysis; Selumetinib
Intervention description: Correlative studies; Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well selumetinib works in treating patients with
      recurrent or persistent endometrial cancer that has come back or is persistent. Selumetinib
      may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed* endometrial epithelial carcinoma, including any of the
             following cell types:

               -  Endometrioid adenocarcinoma

               -  Serous adenocarcinoma

               -  Undifferentiated carcinoma

               -  Clear cell adenocarcinoma

               -  Mixed epithelial carcinoma

               -  Adenocarcinoma not otherwise specified

               -  Mucinous adenocarcinoma

               -  Squamous cell carcinoma

               -  Transitional cell carcinoma

               -  Mesonephric carcinoma

          -  Recurrent or persistent disease that is refractory to curative therapy or established
             treatments

          -  Measurable disease, defined as ≥ 1 lesion that can be measured in ≥ 1 dimension
             (longest dimension to be recorded)

               -  Each lesion must be ≥ 20 mm when measured by conventional techniques (palpation,
                  plain x-ray, CT scan, or MRI) OR ≥ 10 mm when measured by spiral CT scan

          -  Must have ≥ 1 target lesion to be used to assess response, as defined by RECIST
             criteria

               -  Tumors within a previously irradiated field are designated as "non-target"
                  lesions unless progression is documented or a biopsy is obtained to confirm
                  persistence ≥ 90 days following completion of radiotherapy

          -  Must have received 1 prior chemotherapeutic regimen for the management of endometrial
             carcinoma

               -  Chemotherapy administered as a radiosensitizer in conjunction with primary
                  radiotherapy is considered a systemic chemotherapy regimen

          -  Not eligible for a higher priority GOG protocol, if one exists (e.g., any active phase
             III GOG protocol for the same patient population)

          -  No prior or concurrent CNS disease (treated or untreated) by physical examination,
             including primary brain tumor or brain metastases

          -  GOG performance status (PS) 0-2 (for patients who received 1 prior treatment regimen)

          -  GOG PS 0-1 (for patients who received 2 prior treatment regimens)

          -  ANC ≥ 1,500/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Creatinine ≤ 1.5 times upper limit of normal (ULN)

          -  Bilirubin ≤ 1.5 times ULN

          -  SGOT ≤ 2.5 times ULN

          -  Alkaline phosphatase ≤ 2.5 times ULN

          -  PT/INR ≤ 1.5 OR in-range INR (between 2 and 3) if patient is on a stable dose of
             therapeutic warfarin

          -  PTT ≤ 1.5 times ULN

          -  Oxygen saturation ≥ 88% on room air

          -  QTc < 450 msec by EKG

          -  LVEF normal

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for ≥ 6 months after
             completion of study therapy

          -  No neuropathy (sensory or motor) > grade 1

          -  No active infection requiring antibiotics

               -  Uncomplicated urinary tract infection allowed

          -  No other invasive malignancy within the past 5 years except for nonmelanoma skin
             cancer

          -  No serious, non-healing wound, ulcer, or bone fracture

          -  No history of abdominal fistula or gastrointestinal perforation

          -  No intra-abdominal abscess within the past 28 days

          -  No active bleeding or pathological condition that would carry a high risk of bleeding
             (e.g., bleeding disorder, coagulopathy, or tumor involving major vessels)

          -  No seizures not controlled with standard medical therapy

          -  No clinically significant cardiovascular disease including, but not limited to, any of
             the following:

               -  Uncontrolled hypertension, defined as systolic BP > 140 mm Hg or diastolic BP >
                  90 mm Hg

               -  Myocardial infarction or unstable angina within the past 6 months

               -  NYHA class II-IV congestive heart failure

               -  Serious cardiac arrhythmia requiring medication, including atrial fibrillation
                  requiring rate-controlling medication

               -  Peripheral vascular disease ≥ grade 2

               -  Cerebrovascular accident (i.e., CVA, stroke), transient ischemic attack, or
                  subarachnoidal hemorrhage within the past 6 months

          -  No evidence of serious ventricular arrhythmia (i.e., ventricular tachycardia or
             ventricular fibrillation ≥ 3 beats in a row) by EKG

          -  Concurrent low molecular weight heparin for treatment of venous thromboembolic disease
             allowed provided patient is considered clinically stable on this regimen

          -  Recovered from prior surgery, radiotherapy, or chemotherapy

          -  At least 1 week since prior hormonal therapy directed at the malignant tumor

          -  At least 3 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or
             mitomycin C)

          -  At least 3 weeks since other prior therapy directed at the malignant tumor, including
             immunologic agents

          -  One prior cytotoxic regimen for the management of recurrent or persistent endometrial
             disease allowed

          -  No prior non-cytotoxic chemotherapy for the management of endometrial cancer, except
             hormonal therapy

          -  No prior anticancer therapy that contraindicates study therapy

          -  No prior MEK inhibitor AZD6244 or other specific MEK/ERK/MAPK pathway targeted therapy

          -  No prior chemotherapy for any abdominal or pelvic tumor other than for the treatment
             for endometrial cancer within the past 5 years

               -  Prior adjuvant chemotherapy for localized breast cancer allowed provided it was
                  completed > 3 years ago AND the patient remains free of recurrent or metastatic
                  disease

          -  No prior radiotherapy to any portion of the abdominal cavity or pelvis other than for
             the treatment of endometrial cancer within the past 5 years

               -  Prior radiotherapy for localized cancer of the breast, head and neck, or skin is
                  allowed provided it was completed > 3 years ago AND the patient remains free of
                  recurrent or metastatic disease

          -  No concurrent medication that may prolong the QTc interval

          -  No other concurrent investigational therapy

          -  No concurrent combination antiretroviral therapy for HIV-positive patients