A Phase I/II Study of First Line Gemcitabine, Cisplatin and MEK162 in Advanced Biliary Tract Carcinoma
- 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 measurable disease by RECIST 1.1
- 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 < 1.6 mg/dl and/or measured
creatinine clearance from 24-hour urine collection of ≥ 60 ml/min
- Adequate hepatic function defined as total bilirubin ≤ 2 mg/dl, ALT/AST ≤ 5 x ULN.
- Patients with biliary obstruction can join if bilirubin corrects to required limit
after adequate biliary drainage.
Adequate cardiac function defined as ejection fraction ≥ 45% as determined by
transthoracic echocardiogram or MUGA
- Patients who have received prior local therapy, including but not limited to
embolization, chemoembolization, radiofrequency ablation, radiation therapy, 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 within 7 days
prior to study treatment
- 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.
- Ability to understand and the willingness to sign a written informed consent document
- Any previous chemotherapy, biologic therapy, or investigational agent, except for
adjuvant therapy as single agents and/or as radio-sensitizing agents limited to
5-fluorouracil and gemcitabine. Patient must have completed adjuvant therapy no less
than six months prior to accrual.
- Evidence of another active cancer that may influence patient outcome as determined by
the Principal Investigator (PI) or co-Principal Investigator (co-PI), except for
nonmelanoma 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
- Known brain metastases or primary central nervous system tumors with seizures that
are 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
- 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.
- Major surgical procedure within 4 weeks.
- Uncontrolled infection.
- Known or suspected allergy to gemcitabine or cisplatin
- Pregnant (positive pregnancy test)
- Breast-feeding should be discontinued if a nursing mother is to be treated on
- Any condition that impairs patient's ability to swallow whole pills
- Malabsorption problem that may limit or inhibit the absorption of MEK 162
- Patients with a history or current known evidence of central serous retinopathy
(CSR), retinal vein occlusion (RVO) or ophthalmopathy at baseline that would be
considered a risk factor for CSR or RVO.
- History of any organ or bone marrow transplant.