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BIBW 2992 as add-on to Gem/Cis in Advanced Biliary Tract Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Johannes Gutenberg University Mainz
Sponsor:
Information provided by (Responsible Party):
PD Dr Markus Möhler, Johannes Gutenberg University Mainz
ClinicalTrials.gov Identifier:
NCT01679405
First received: August 17, 2012
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
Metastatic Disease
Drug: BIBW 2992
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Johannes Gutenberg University Mainz:

Primary Outcome Measures:
  • number of adverse events [ 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. ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: Time from start of treatment to first documentation of objective tumour progression or to death due to any cause, whichever occurs first. Estimated time period: up to 76 weeks ] [ Designated as safety issue: No ]

    Progression free survival and overall survival curves will be estimated using the Kaplan-Meier method.

    Median progression-free survival time and median overall survival time including the 95% confidence intervals will be determined using Kaplan-Meier estimates, if possible.


  • Overall survival (OS) [ Time Frame: Time from start of treatment to death due to any cause. Time to last observation will be used if a patient has not died and OS for the patient will be considered censored. Estimated time period: up to 76 weeks ] [ Designated as safety issue: No ]

    Progression free survival and overall survival curves will be estimated using the Kaplan-Meier method.

    Median progression-free survival time and median overall survival time including the 95% confidence intervals will be determined using Kaplan-Meier estimates, if possible.


  • Objective response rate [ Time Frame: Objective Response rate is defined as a best response rating of Complete Response (CR) and Partial Response (PR) according to Recist 1.1. Estimated time period: up to 76 weeks ] [ Designated as safety issue: No ]

    Objective response rate and tumour control rate will be analysed by providing absolute and relative frequencies of the categories.

    Best response is defined as the best tumour response (confirmed partial or complete response, stable disease) that is achieved until PD according to Recist 1.1.


  • Tumor control rate [ Time Frame: Tumour control rate is defined as a best response rating of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) according to Recist 1.1. Estimated time period: up to 76 weeks ] [ Designated as safety issue: No ]

    Objective response rate and tumour control rate will be analysed by providing absolute and relative frequencies of the categories.

    Best response is defined as the best tumour response (confirmed partial or complete response, stable disease) that is achieved until PD according to Recist 1.1.



Estimated Enrollment: 22
Study Start Date: August 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBW 2992 added to the standard therapy

In part A the maximum tolerated dose (MTD) of oral BIBW 2992 administered continuously added 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.

In part B (phase Ib) of this study, the MTD cohort may be expanded up to 7 further patients and one or two additional study centers may be recruited.

During Part B dose adjustments, based on individual patient's tolerability, are possible. A dose increase of BIBW 2992 higher than 40 mg daily per os is not permitted.

Drug: BIBW 2992
single arm study
Other Name: Gemcitabine and Cisplatin

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01679405

Contacts
Contact: Markus Moehler, Prof. Dr. med. 0049 6131 17 ext 5712 Markus.Moehler@unimedizin-mainz.de

Locations
Germany
I. Medizinische Klinik und Poliklinik der Universitätsmedizin Recruiting
Mainz, Germany, 55131
Contact: Markus Moehler, Prof. Dr. med.    0049 6131 17 ext 5712    Markus.Moehler@unimedizin-mainz.de   
Sponsors and Collaborators
Johannes Gutenberg University Mainz
Investigators
Principal Investigator: Markus Moehler, Prof. Dr. med. University Medical Center of the Johannes Gutenberg-University Mainz
  More Information

No publications provided

Responsible Party: PD Dr Markus Möhler, Principal Investigator, Johannes Gutenberg University Mainz
ClinicalTrials.gov Identifier: NCT01679405     History of Changes
Other Study ID Numbers: BIBW 2992
Study First Received: August 17, 2012
Last Updated: May 13, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Johannes Gutenberg University Mainz:
metastatic biliary tract cancer

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes
Cisplatin
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014