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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

Phase 1
18 Years
Open (Enrolling)
Metastatic Disease

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Trial Information

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

The primary objective is safety and toxicity, including maximum tolerated dose, of BIBW 2992
when given as add-on therapy to Gem/Cis.

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

number of adverse events

Outcome Description:

In part A the maximum tolerated dose (MTD) of BIBW 2992 administered continuously to the standard therapy of Gemcitabine / Cisplatin (Gem/Cis) (administered together on day 1 and 8 of a three-week cycle) will be evaluated in a 2 step dose escalation. Safety and toxicity will be evaluated as described and considered primary for part B of the study.

Outcome Time Frame:

No DLT within 21 days after start of therapy; safety and toxicity assessment from time of signing informed consent up to 30 days after end of therapy. Treatment period: up to eight cycles. 12 months follow-up period.

Safety Issue:


Principal Investigator

Markus Moehler, PD Dr. med.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Medical Center of the Johannes Gutenberg-University Mainz


Germany: Federal Institute for Drugs and Medical Devices

Study ID:

BIBW 2992



Start Date:

August 2012

Completion Date:

June 2014

Related Keywords:

  • Metastatic Disease
  • metastatic biliary tract cancer
  • Neoplasm Metastasis
  • Biliary Tract Neoplasms