Cediranib Maleate and Combination Chemotherapy in Treating Patients With Advanced Biliary Cancers
Condition: Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Periampullary Adenocarcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer
MeSH terms: Liver Neoplasms; Cholangiocarcinoma; Gallbladder Neoplasms; Bile Duct Neoplasms; Recurrence
Intervention: cediranib maleate; oxaliplatin; leucovorin calcium; fluorouracil
Intervention description: Given PO; Given IV; Given IV; Given IV
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Cediranib; Calcium; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving cediranib maleate together with combination
      chemotherapy works in treating patients with advanced biliary cancers. Cediranib maleate may
      stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by
      blocking blood flow to the tumor. Drugs used in chemotherapy, such as oxaliplatin, leucovorin
      calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either
      by killing the cells or by stopping them from dividing. Giving cediranib maleate together
      with combination chemotherapy may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with histopathological or cytopathological diagnosis of advanced biliary
             carcinoma (gallbladder cancer, cholangiocarcinoma, ampullary cancer) not amenable to
             conventional surgical approach are eligible

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >
             20 mm with conventional techniques or as > 10 mm with spiral CT scan

          -  No patients with untreated brain metastases

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)

          -  Life expectancy of greater than 12 weeks

          -  White blood cell (WBC)/leukocytes ≥ 3,000/μL

          -  Absolute neutrophil count ≥ 1,500/μL

          -  Platelets ≥ 100,000/μL

          -  Hemoglobin ≥ 9 g/dL

          -  Total bilirubin ≤ 3 mg/dL

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤
             2.5 times institutional upper limit of normal

          -  Creatinine within normal institutional limits OR calculated creatinine clearance ≥ 60
             mL/min

          -  No patients with proteinuria not meeting the criteria below; urine sample must be
             tested by urine protein:creatinine (UPC) ratio or by urinalysis method within 1 week
             of starting study treatment; depending upon the testing method used, the following
             criteria must be met:

               -  UPC ratio must be < 1.0; if UPC ratio is ≥ 1.0, a 24-hour urine specimen must be
                  collected and must demonstrate < 1 g of protein

               -  Urinalysis must indicate 0-1+ protein; if urinalysis reading is ≥ 2+, a 24-hour
                  urine specimen must be collected and must demonstrate < 1 g of protein

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use adequate contraception (hormonal or barrier method of birth
             control; abstinence) before and during study treatment

               -  Acceptable contraception includes abstinence, oral contraceptives, intra-uterine
                  device (IUD), diaphragm, Norplant, approved hormone injections, condoms, or
                  documentation of medical sterilization

          -  Patients with evidence of heart disease must be New York Heart Association (NYHA)
             Class I or II

               -  NYHA Class II patients controlled with treatment are considered at increased risk
                  for compromised left ventricular ejection fraction (LVEF) and will undergo
                  increased cardiac monitoring

          -  No patients with other active invasive cancers except nonmelanoma skin cancer or
             carcinoma in-situ of the cervix

               -  History of prior cancer is allowed as long as there has been no evidence of
                  disease within the past 5 years

          -  No patients with mean corrected QT interval (QTc) > 480 msec (with Bazett's
             correction) in screening electrocardiogram or history of familial long QT syndrome

          -  No patients with uncontrolled hypertension defined as systolic blood pressure (BP) ≥
             140 mm Hg or diastolic BP ≥ 90 mm Hg, with or without anti-hypertensive medication or
             history of hypertensive crisis or hypertensive encephalopathy

               -  Patients with initial BP elevations are eligible once their BP is controlled to
                  above parameters

          -  No patients with uncontrolled intercurrent illness including, but not limited to:

               -  Hypertension (> 140/90 mm Hg)

               -  Chronic or active infection requiring chronic suppressive antibiotics

               -  History of or symptomatic congestive heart failure requiring chronic medical
                  therapy

               -  NYHA class III or IV heart disease

               -  Unstable angina pectoris within 180 days prior to starting study treatment

               -  Myocardial infarction within 180 days prior to study treatment

               -  Gastroduodenal ulcer(s) determined by endoscopy to be active within 180 days
                  prior to study treatment

               -  Serious or non-healing wound, skin ulcers, or bone fracture

               -  Any significant bleeding that is not related to the primary tumor within 180 days
                  prior to study treatment

               -  Known bleeding diathesis or coagulopathy

               -  Paresthesias, peripheral sensory neuropathy > gr. 1 per Common Terminology
                  Criteria for Adverse Events (CTCAE) v.4, or peripheral motor neuropathy ≥ gr. 2
                  per CTCAE v.4

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

          -  No patients with history of transient ischemic attack (TIA) or cerebrovascular
             accident (CVA) within 180 days prior to study treatment, symptomatic peripheral
             ischemia; history of arterial thrombotic event within 180 days prior to study
             treatment; gastrointestinal (GI) perforation within 180 days prior to study treatment

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible

          -  Patients who are chemotherapy naive unless chemotherapy was given as adjuvant
             post-surgical treatment and at least 6 months have elapsed since adjuvant chemotherapy

          -  No patients who have had major surgical procedures, open biopsies, or significant
             traumatic injury within 28 days prior to study treatment

          -  Chemotherapy for prior cancer is permitted

          -  Eligibility of patients receiving any medications or substances known to affect or
             with the potential to affect the activity or PK of AZD2171 will be determined
             following review of their case by the Principal Investigator

               -  Efforts should be made to switch patients with brain metastases who are taking
                  enzyme-inducing anticonvulsant agents to other medications

          -  Patients may not be receiving any other investigational agents nor have participated
             in an investigational trial within the past 30 days

          -  Patients may not be receiving any medication that may markedly affect renal function
             (e.g., vancomycin, amphotericin, pentamidine)

          -  Patients may not be receiving therapeutic doses of Coumadin or equivalent

          -  No patients requiring drugs with proarrhythmic potential