A Phase II Study of Gemcitabine and Cisplatin Plus Sorafenib in Patients With Advanced Biliary Tract Carcinomas Naïve to Systemic Therapy
- 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 ≥
- 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
- 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
- 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
- Ability to understand and the willingness to sign a written informed consent document
- 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
- Uncontrolled infection.
- Known or suspected allergy to sorafenib or any agent given in the course of this
- Pregnant (positive pregnancy test)
- Breast-feeding should be discontinued if the mother is to be treated on clinical
- 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