Bevacizumab and Temsirolimus in Treating Patients With Recurrent or Persistent Endometrial Cancer
Condition: Recurrent Endometrial Carcinoma
MeSH terms: Carcinoma; Endometrial Neoplasms; Recurrence
Intervention: bevacizumab; temsirolimus
Intervention description: Given IV; Given IV
Intervention MeSH terms: Sirolimus; Bevacizumab; Antineoplastic Agents, Immunological; Temsirolimus; MTOR Inhibitors; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying the side effects of giving bevacizumab together with
      temsirolimus and to see how well it works in treating patients with recurrent or persistent
      endometrial cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in
      different ways. Some block the ability of tumor cells to grow and spread. Others find tumor
      cells and help kill them or carry tumor-killing substances to them. Temsirolimus may stop the
      growth of tumor cells by blocking some of the enzymes needed for their growth. Giving
      bevacizumab together with temsirolimus may kill more tumor cells.
    

Eligibility criteria:

        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