Open-label, Uncontrolled, Multicenter Phase I/Ib Trial to Investigate Safety and Efficacy of BIBW 2992 and Standard Gemcitabine/Cisplatin in Chemo-naïve Patients With Advanced Biliary Tract Adenocarcinoma
Inclusion Criteria:
- Male and female patients aged ≥ 18 years
- Signed and dated written informed consent,
- Histologically confirmed adenocarcinoma of the gallbladder or intrahepatic bile ducts
or histologically proven hepatic metastases of an earlier resected and histologically
proven biliary tract cancer
- with pain and biliary obstruction controlled
- adequate biliary drainage, no uncontrolled infection
- ECOG Performance Status of 0-1
- LFTs: bilirubin (total) ≤ 1.5 x ULN, ALT/ AST/ alkaline phosphatase ≤ 3 2.5 x
ULN (≤ 5 x ULN if liver metastases are present)
- No prior systemic treatment i) previous adjuvant chemotherapy is allowed
(completed ≥ 6 months if containing Gemcitabine or platinum salts); ii)
previous irradiation (external radiotherapy, brachytherapy, chemoembolization)
and PDT are allowed, provided that there is still at least one unidimensionally
measurable target lesion in an untreated area
- Resolution of all side effects of prior surgical procedures to CTCAE grade ≤ 1
(except for the laboratory values specified below)
- At least 4 weeks from any major surgery (at first dose of study drug)
- Life expectancy of at least 12 weeks.
- Cardiac left ventricular function with resting ejection fraction (LVEF) ≥ 50%
- Adequate bone marrow, liver and renal function as assessed by the following
laboratory requirements to be conducted within 7 days prior to start of therapy:
- Haemoglobin > 10.0 g/dl (=6.2 mmol/l), blood transfusion is allowed
- Absolute neutrophil count (ANC) > 1,500/mm3 (=1.5x 109/L)
- Platelet count ≥ 100,000/μl (=100x 109/L)
- Total bilirubin ≤ 1.5 times the upper limit of normal
- ALT and AST ≤ 2.5 x institutional upper limit of normal (in case of liver
metastases: ALT and AST ≤ 5 x institutional upper limit of normal)
- Prothrombin rate > 60% or INR < 1.5
Main exclusion criteria
- Large surgery (except diagnostic biopsy) or smaller surgical procedures, external
radiotherapy, brachytherapy, or PDT within 30 days prior to start of treatment.
- Other tumor type than adenocarcinoma (e.g. leiomyosarcoma, lymphoma) or a second
cancer except in patients with squamous or basal cell carcinoma of the skin or
carcinoma in situ of the cervix which has been effectively treated.
- History of acute cardiac disease: congestive heart failure > NYHA class 2; active CAD
(MI more than 6 months prior to study entry is allowed);
- Patients on immunosuppressant therapy or with known HIV infection
- Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
- History of organ allograft
- Pregnant or breast-feeding patients.
- Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation
- Any condition that is unstable or could jeopardize the safety of the patient and
their compliance in the study
- Gastrointestinal (GI) tract disease resulting in an inability to take oral medication
or a requirement for IV alimentation, prior surgical procedures affecting absorption,
or active peptic ulcer disease
- History of pre-existing interstitial lung disease (ILD)
- Patients with untreated or symptomatic brain metastases.
- Persistent Grade 2 or greater neurotoxicity / neuropathy from any cause