Bevacizumab and Temsirolimus in Treating Patients With Recurrent or Persistent Endometrial Cancer

This is an interventional treatment trial for Recurrent Endometrial Carcinoma Read More

Inclusion Criteria:

• Histologically confirmed endometrial carcinoma (from primary tumor) 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 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan

• Must have ≥ 1 target lesion to assess response as defined by RECIST

  • Tumors within a previously irradiated field are designated as "non-target" lesions in the absence of documented disease progression or a biopsy to confirm persistence for ≥ 90 days after completion of radiotherapy

• Must have received 1 prior chemotherapeutic regimen for management of endometrial carcinoma

  • May have received 1 additional cytotoxic regimen for management of this disease
• Not eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, including any active GOG Phase III protocol for patients with endometrial carcinoma
• No history or evidence of CNS disease, including primary brain tumor or any brain metastases upon physical examination
• GOG performance status (PS) 0-2 (for patients who have received 1 prior regimen) OR PS 0-1 (for patients who have received 2 prior regimens)
• ANC ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• 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
• Urine protein:creatinine ratio < 1.0 OR urine protein < 1,000 mg by 24-hour urine collection
• 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
• Fasting cholesterol < 350 mg/dL
• Fasting triglycerides < 400 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Seizures allowed provided they are controlled with standard medical therapy
• No active infection requiring antibiotics, except uncomplicated urinary tract infection
• No active bleeding or pathologic conditions that carry high risk of bleeding, (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels)

• No serious, non-healing wound, ulcer, or bone fracture, including abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 3 months

  • No prior underlying lesions that caused the fistula or perforation that have not been corrected
• No prior interstitial pneumonitis

• No clinically significant cardiovascular disease, including any of the following:

  • Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg
  • Myocardial infarction or unstable angina within the past 6 months
  • New York Heart Association class II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Peripheral vascular disease ≥ grade 2
• No cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months

• No uncontrolled diabetes

  • Hemoglobin A1C < 10
• No other invasive malignancies within the past 5 years, except nonmelanoma skin cancer and other specific malignancies (e.g., localized breast, head and neck, or skin cancer that completed treatment > 3 years prior to study and remain disease-free)
• No significant traumatic injury within the past 28 days
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
• Concurrent prophylactic or therapeutic anticoagulation* (e.g., warfarin) allowed
• Recovered from recent surgery, radiotherapy, or chemotherapy
• No prior bevacizumab or other VEGF pathway-targeted therapy
• No prior temsirolimus, everolimus, deforolimus, sirolimus, or any other mTor/PI3K pathway-targeted therapy

• No prior non-cytotoxic chemotherapy for management of this disease, except hormonal therapy

  • At least 1 week since prior hormonal therapy directed at the malignant tumor
• No prior therapy that contraindicates this protocol therapy

• No prior radiotherapy to any portion of the abdominal cavity or pelvis within the past 5 years, except treatment of endometrial cancer

  • Prior radiotherapy for localized cancer of the breast, head and neck, or skin is allowed, provided it was completed > 3 years prior to study entry and patient remains free of recurrent or metastatic disease

• No prior chemotherapy for any abdominal or pelvic tumor within the past 5 years, except treatment of endometrial cancer

  • Prior adjuvant chemotherapy for localized breast cancer allowed, provided it was completed > 3 years prior to study entry and the patient remains free of recurrent or metastatic disease
• Prior treatment with an anthracycline (i.e., doxorubicin and/or liposomal doxorubicin) allowed provided ejection fraction < 50%
• More than 28 days since prior major surgery or open biopsy
• More than 7 days since minor surgical procedures, fine needle aspirates, or core biopsies
• At least 3 weeks since prior therapy directed at the malignant tumor, including immunologic agents
• No concurrent major surgery
• No concurrent prophylactic filgrastim (G-CSF) or thrombopoietic agents
• No concurrent amifostine or other protective reagents