Clinical trial NCT00238212 (phase 2, status: completed)
Conditions: adenocarcinoma of the extrahepatic bile duct, adenocarcinoma of the gallbladder, adenocarcinoma with squamous metaplasia of the gallbladder, cholangiocarcinoma of the extrahepatic bile duct, cholangiocarcinoma of the gallbladder, recurrent extrahepatic bile duct cancer, recurrent gallbladder cancer, squamous cell carcinoma of the gallbladder, unresectable extrahepatic bile duct cancer, unresectable gallbladder cancer
ICD codes: C22.0, C22.1, C4A.9, C7B.1, D09.9, C4A.0, C4A.31
Drugs: sorafenib tosylate
SMILES: CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a cytologically or pathologically confirmed diagnosis of
             cholangiocarcinoma or gallbladder carcinoma

               -  The pathologic confirmation of gallbladder or cholangiocarcinoma may be made from
                  the primary or metastatic site; biopsy of the gallbladder or bile duct mass is
                  not necessary; patients with pathologic confirmation of adenocarcinoma of a
                  metastatic site, along with clinical documentation of gallbladder or bile duct
                  involvement and no evidence of another primary are also eligible; if clinical
                  documentation of gallbladder or bile duct involvement is not possible because of
                  removal of the organ, a clinically and/or radiographically consistent picture
                  plus pathologic findings from the metastatic site that are determined to be
                  consistent with cholangiocarcinoma are acceptable

               -  Eligible pathologic type: Patient must have one of the following subtypes:
                  adenocarcinoma NOS, papillary carcinoma, adenocarcinoma, intestinal type, clear
                  cell adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma,
                  squamous cell carcinoma, adenosquamous carcinoma, small cell carcinoma,
                  undifferentiated carcinoma, carcinoma NOS; patient must not have carcinoid tumors
                  or sarcomas

          -  Patient must have locally advanced or distant metastatic disease that is not
             surgically curable

          -  Patient must have measurable disease; x-rays, scans or physical examinations used for
             tumor measurement must have been completed within 28 days prior to registration;
             x-rays, scans or other tests for assessment of non-measurable disease must have been
             performed within 42 days prior to registration; all disease must be assessed

          -  Institutions are required to submit paraffin-embedded specimens

          -  Institutions are required to seek additional patient consent for submission of blood

          -  Patient may have had prior surgery, including surgery for their gallbladder or
             cholangiocarcinoma; patients must be at least 14 days beyond any major surgery, and
             recovered from all effects of surgery

          -  Patient must not have received prior therapy for unresectable or metastatic disease;
             patient may have received prior chemotherapy, hormonal therapy, immunotherapy,
             radiation therapy (to less than 25% of bone marrow only) or chemoradiotherapy as
             neoadjuvant or adjuvant treatment; this must have been completed at least 12 months
             prior to documented recurrence or metastatic disease; patient must have recovered from
             all radiation induced toxicities

          -  Prior radiation therapy to metastatic sites, such as bone, is allowed as long as the
             patient has measurable lesion(s) that were not treated with radiation therapy; at
             least 28 days must have elapsed since completion of radiation therapy, and patient
             must have recovered from all effects

          -  Patient must not have received prior BAY 43-9006 or any inhibitor of VEGFR or the MAPK
             pathway

          -  Patient must have Zubrod performance status of 0-1

          -  Total serum bilirubin =< 3 x the institutional upper limit of normal (IULN)

          -  Serum transaminase (SGOT or SGPT) =< 2.5 x IULN; if liver metastasis is present, SGOT
             or SGPT must be =< 5 x IULN

          -  Patients with biliary obstruction must have decompressions of the biliary tree by ERCP
             and stenting or percutaneous drainage

          -  Serum creatinine =< 1.5 x IULN OR measured creatinine clearance >= 60 mL/min OR
             estimated creatinine clearance >= 60 mL/min

          -  Leukocyte count >= 3,000/mcL

          -  ANC >= 1,000/mcL

          -  Platelets >= 100,000/mcL

          -  PT, INR and PTT =< IULN

          -  Patients must not be taking the cytochrome P450 enzyme-inducing antiepileptic drugs
             (phenytoin, carbamazepine, and Phenobarbital), rifampin, or St. Johns Wort

          -  Patient must not be on therapeutic anticoagulation; prophylactic anticoagulation
             (i.e., low dose warfarin) of venous or arterial access devices is allowed provided
             that the requirements for PT, INR and PTT are met

          -  Patient must not have any evidence of bleeding diathesis

          -  Patients must not have clinically significant cardiac disease that is not well
             controlled by medication (e.g., congestive heart failure, symptomatic coronary artery
             disease and cardiac arrhythmias) or myocardial infarction within 12 months prior to
             registration

          -  Patient must not have uncontrolled hypertension

          -  Patient must not have known brain metastases because of their poor prognosis and
             because they often develop progressive neurologic dysfunction that would confound the
             evaluation of neurologic and other adverse events

          -  Patient must either be able to swallow and/or receive enteral medications via
             gastrostomy feeding tube; tablets must not be crushed; patient must have the ability
             to absorb medication (i.e., no malabsorption syndrome); patient must not have
             intractable nausea or vomiting

          -  Patient must have no plans to receive concurrent chemotherapy, hormonal therapy,
             radiotherapy, immunotherapy or any other type of therapy for treatment of cancer while
             on this protocol; radiation for palliation to metastatic sites is allowed as long gas
             the target lesions are not irradiated

          -  Women/men of reproductive potential must agree to use an adequate contraception
             (hormonal or barrier method of birth control or abstinence) prior to study entry and
             for the duration of protocol treatment; post-menopausal women must be amenorrheic for
             at least 12 months to be considered of non-childbearing potential; pregnant or nursing
             women are not eligible for this protocol; should a woman become pregnant or suspect
             she is pregnant while participating in this study, she should inform her treating
             physician immediately; breastfeeding must be discontinued if the mother is treated
             with BAY 43-9006

          -  HIV-positive patients must have a CD4 count > 500 and must have no active
             opportunistic infection; in addition, patient must not be receiving combination
             anti-retroviral therapy

          -  No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
             stage I or II cancer from which the patient is currently in complete remission, or any
             other cancer from which the patient has been disease free for five years

          -  If day 14, 28 or 42 falls on a weekend or holiday, the limit may be extended to the
             next working day

               -  In calculating days of tests and measurements, the day a test or measurement is
                  done is considered day 0; therefore, if a test is done on a Monday, the Monday
                  two weeks later would be considered day 14; this allows for efficient patient
                  scheduling without exceeding the guidelines

          -  All patients must be informed of the investigational nature of this study and must
             sign and give written informed consent in accordance with institutional and federal
             guidelines

          -  At the time of patient registration, the treating institution's name and ID number
             must be provided to the Data Operations Center in Seattle in order to ensure that the
             current (within 365 days) date of institutional review board approval for this study
             has been entered into the data base