BIBW 2992 as add-on to Gem/Cis in Advanced Biliary Tract Cancer
Condition: Metastatic Disease
MeSH terms: Neoplasm Metastasis
Intervention: BIBW 2992
Intervention description: once daily per os
Intervention MeSH terms: Cisplatin; Gemcitabine; Afatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: For Part A of the study a standard 3+3 design was used. The recruitment was carried out in cohorts. Subjects were not allowed to participate in both cohorts. If the maximum tolerated dose was found there should be additional patients recruited to confirm the maximum tolerated dose (part B)
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: metastatic biliary tract cancer

Summary:

      An open-label, uncontrolled, multicenter phase I/Ib trial to investigate safety and efficacy
      of BIBW 2992 added to the standard therapy of Gemcitabine/Cisplatin in chemo-naïve patients
      with advanced and/or metastatic adenocarcinoma of the biliary tract
    

Eligibility criteria:

        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 extrahepatic bile ducts (metastasized) or histologically proven hepatic metastases
             of an earlier resected and histologically proven biliary tract cancer or a Klatskin
             tumour (hilar cholangiocarcinoma)

               -  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