SCCA Gynecologic Cancer Clinical Trials

The primary objectives of this study are to determine the response at 6 months of patients with persistent or recurrent endometrial carcinoma treated with cediranib maleate.

• Histologically confirmed primary endometrial carcinoma including any of the following epithelial 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

• Recurrent or persistent disease

  • Refractory to curative therapy or established treatments

• Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded)

  • Lesion must be ≥ 10 mm by CT scan, MRI, or caliper measurement by clinical exam OR ≥ 20 mm by chest x-ray
  • Lymph nodes must be > 15 mm in short axis by CT scan or MRI

• Patient must have ≥ 1 "target lesion" to assess response as defined by RECIST v. 1.1

  • Tumors within a previous irradiated field are designated as non-target lesions unless progression is documented OR a biopsy is obtained to confirm persistence of disease ≥ 90 days after completion of radiotherapy
• Patient must not be eligible for a higher priority GOG protocol, if one exists

• Must have had 1 prior chemotherapeutic regimen for management of endometrial cancer that may include 1 of the following:

  • Chemotherapy

  • Chemotherapy and radiotherapy

    • Chemotherapy in conjunction with primary radiotherapy as a radio-sensitizer will be counted as a systemic chemotherapy regimen
  • Consolidation and/or maintenance therapy
• No CNS disease, including primary brain tumor or brain metastases

PATIENT CHARACTERISTICS:

• GOG performance status (PS) 0-2 (for patients who received 1 prior therapeutic regimen) OR GOG PS 0-1 (for patients who received 2 prior regimens)
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine ≤ 1.5 times upper limit of normal (ULN) OR Creatinine clearance ≥ 60 mL/min
• Urine protein:creatinine (UPC) ratio < 1.0 g
• Bilirubin ≤ 1.5 times ULN
• AST ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• INR ≤ 1.5 times ULN (between 2 and 3 for patients on stable dose of therapeutic warfarin)
• PTT ≤ 1.5 times ULN
• Amylase and lipase normal
• Thyroid stimulation hormone (TSH) and free thyroxine (Free T4) normal
• Peripheral neuropathy (sensory and motor) ≤ grade 1
• Negative pregnancy test
• Not pregnant or nursing
• Fertile patients must use effective contraception

• No active infection requiring antibiotics

  • Uncomplicated urinary tract infection allowed
• No invasive malignancies within the past 3 years except nonmelanoma skin cancer or curatively treated localized cancer of the breast, head and neck, or skin

• No serious non-healing wound, ulcer, or bone fracture, including the following:

  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days

• No active bleeding or pathological conditions that carry high-risk of bleeding, including the following:

  • Known bleeding disorder
  • Coagulopathy disorder
  • Tumor involving major vessels
• No uncontrolled seizures with standard medical therapy

• No clinically significant cardiovascular disease including, but not limited to, any of the following:

  • Uncontrolled hypertension (defined as systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg despite optimized antihypertensive therapy)
  • Myocardial infarction or unstable angina within the past 6 months

  • NYHA grade II-IV congestive heart failure or serious cardiac arrhythmia requiring medication

    • Patients who received prior anthracycline treatment, including doxorubicin hydrochloride and/or liposomal doxorubicin, and have an ejection fraction < normal are not eligible for this study
  • Peripheral vascular disease ≥ grade 2 as assessed by NCI CTCAE
  • History of cerebrovascular accident (e.g., CVA, stroke), transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
  • Mean QTc > 500 msec or history of familial long QT syndrome
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

• Recovered from recent surgery, radiotherapy, or chemotherapy
• At least 1 week since prior hormonal therapy directed at the malignant tumor
• At least 3 weeks since any other prior anticancer therapy

• One prior cytotoxic regimen for management of recurrent or persistent disease allowed

  • 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

• No prior non-cytotoxic chemotherapy for management of recurrent or persistent disease

  • Prior hormonal therapy allowed
• No prior cediranib maleate or other VEGF pathway-targeted therapy
• No prior cancer treatment that contraindicates this protocol therapy

• No prior radiotherapy to any portion of the abdominal cavity or pelvis within the past 3 years other than treatment for endometrial cancer

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

• No prior chemotherapy for any abdominal or pelvic tumor other than for endometrial cancer within the past 5 years

  • Prior adjuvant chemotherapy for localized breast cancer allowed provided it was completed > 3 years and patient remains free of recurrent or metastatic disease
• No major surgical procedure, open biopsy, or significant traumatic injury within the past 28 days
• No anticipation of major surgical procedure during the course of the study
• No minor surgical procedures, fine needle aspirates, or core biopsies within the past 7 days
• No concurrent amifostine or other protective reagents