Gemcitabine and Cisplatin Plus Sorafenib in Patients With Advanced Biliary Tract Carcinomas Naive to Systemic Therapy
Condition: Extrahepatic Bile Duct Cancer; Gallbladder Cancer
MeSH terms: Gallbladder Neoplasms; Bile Duct Neoplasms; Cholangiocarcinoma
Intervention: Gemcitabine; Cisplatin; Sorafenib
Intervention description: Gemcitabine: 800 mg/m^2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment.; 20 mg /m^2 over 30 minutes IV, weekly for 2 weeks, followed by a week off treatment.; 400 mg PO once a day continuously.
Intervention MeSH terms: Gemcitabine; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GALL BLADDER; BILE DUCTS; BAY 43-9006; SORAFENIB; CISPLATIN; GEMCITABINE; 09-029

Summary:

      The purpose of this study is to test an investigational combination of drugs for bile duct or
      gallbladder cancers.

      Gemcitabine and cisplatin are two forms of chemotherapy commonly used in combination to treat
      bile duct and gallbladder cancers. We are looking to improve treatment results. We will
      attempt to do so by adding sorafenib (a type of monoclonal antibody) to your treatment plan.
      Sorafenib acts by attaching to blocking specific targets on cells. These targets may help the
      cancer cells grow and divide. This study will help answer the question of whether sorafenib
      is a helpful drug in patients with bile duct or gallbladder cancers when given with
      gemcitabine and cisplatin.

      This study is a phase 2 study. The purpose of a phase 2 study is to find out what effects,
      good and/or bad, sorafenib in combination with gemcitabine and cisplatin has on advanced bile
      duct and gallbladder cancers.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically / cytologically verified, non-resectable, recurrent, or metastatic
             biliary tract carcinoma including intrahepatic cholangiocarcinoma, extrahepatic
             cholangiocarcinoma and gallbladder carcinoma. Combined cholangiocarcinoma and
             hepatocellular carcinoma is allowed.Patients must have uni-dimensionally measurable
             disease by x-ray, CT scan, MRI scan or physical examination.

          -  KPS ≥ 80%

          -  Age ≥ 18 years

          -  Adequate bone marrow function defined as: Hb ≥ 8 g/dl, ANC ≥ 1.5 K/mcL, Platelets ≥
             100 K/mcL

          -  Adequate renal function defined as Serum creatinine < 2.0 mg/dl and calculated
             creatinine clearance ≥ 60 ml/min using the formula:

          -  Cockcroft-Gault formula:

        Cockcroft-Gault Formula - MALES CrCl = (140 - age[years]) (body wt[kg]) (72) (serum
        creatinine [mg/dL]) Cockcroft-Gault Formula - FEMALES CrCl = 0.85 x male value

          -  If calculated creatinine clearance is not within range using the above formula, then
             measured levels from 24-hour urine collection may be used to calculate the creatinine
             clearance.

          -  Adequate hepatic function defined as total bilirubin ≤ 2 mg/dl, ALT/AST/ ≤ 3 x ULN (≤
             5 if liver metastases). Patients with biliary obstruction can join if bilirubin
             corrects to required limit after adequate biliary drainage.

          -  PT/INR ≤ 1.7 and PTT ≤ 1.5 x ULN, unless the patient is receiving anti-coagulation
             therapy with agents such as warfarin or heparin

          -  Patients who have received prior local therapy, i.e. embolization, radiation therapy,
             etc. (except for chemoembolization) are eligible provided that measurable disease
             falls outside the treatment field or within the field but has shown an increase of
             ≥20% in the size. Prior local therapy must be completed at least 4 weeks prior to the
             baseline scan

          -  Women of childbearing potential must have a negative pregnancy test.

          -  Men and women of childbearing potential must be willing to consent to using effective
             contraception while on treatment and for at least 3 months thereafter. Patients are
             encouraged to continue barrier method contraception for two years or longer after
             treatment.

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Any previous chemotherapy, biologic therapy, or investigational agent, except for 5-FU
             or gemcitabine given as adjuvant therapy as single agents and/or as radio-sensitizing
             agents. Patient must have completed adjuvant therapy no less than six months prior to
             accrual. Patients with previous significant allergic hypersensitivity to gemcitabine
             are excluded.

          -  Evidence of another active cancer that may influence patient outcome as determined by
             the Principal Investigator, except for non-melanoma skin carcinoma, melanoma in-situ,
             in-situ carcinoma of the cervix curatively treated, treated superficial bladder
             cancer, and adenocarcinoma of the prostate that has been surgically treated with a
             post-treatment PSA that is non-detectable.

          -  Known brain metastases

          -  History of primary central nervous system tumors or brain metastases, and/or seizures
             not well controlled with standard medical therapy.

          -  Uncontrolled intercurrent illness including, but not limited to psychiatric
             illness/social situations that would limit compliance with study requirements.

          -  Known HIV positive patient

          -  Blood Pressure of > 150/100 mm Hg

          -  Significant cardiovascular disease including congestive heart failure (New York Heart
             Association Class II or higher) or active angina pectoris.

          -  History of a myocardial infarction within 6 months.

          -  History of a stroke or transient ischemic attack within 6 months.

          -  Clinically significant peripheral vascular disease.

          -  Evidence of bleeding diathesis or coagulopathy.

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks.

          -  Uncontrolled infection.

          -  Known or suspected allergy to sorafenib or any agent given in the course of this
             trial.

          -  Pregnant (positive pregnancy test)

          -  Breast-feeding should be discontinued if the mother is to be treated on clinical
             trial.

          -  Serious non-healing wound, ulcer, or bone fracture

          -  Use of St. John's Wort or rifampin (rifampicin)

          -  Any condition that impairs patient's ability to swallow whole pills

          -  Any malabsorption problem