<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02975141</url>
  </required_header>
  <id_info>
    <org_study_id>2015-004065-86</org_study_id>
    <nct_id>NCT02975141</nct_id>
  </id_info>
  <brief_title>Afatinib and Gemcitabine/Nab-paclitaxel in Metastatic Pancreatic Cancer</brief_title>
  <acronym>AFFECT</acronym>
  <official_title>Gemcitabine and Nab-Paclitaxel Combined With the Oral Irreversible ErbB Family Blocker Afatinib in Patients With Metastatic Pancreatic Cancer: A Phase Ib Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PD Dr. med. Volker Heinemann</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Technical University of Munich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Cologne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ludwig-Maximilians - University of Munich</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study sets out to determine the maximum tolerated dose (MTD) of afatinib in combination&#xD;
      with gemcitabine/nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma.&#xD;
      The identified MTD will serve as recommended phase II dose (RP2D).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pancreatic ductal adenocarcinoma (PDAC) remains an almost uniformly lethal disease. Although&#xD;
      there has been significant progress in understanding of the underlying molecular biology of&#xD;
      pancreatic cancer, this progress has not translated into substantially better treatments.&#xD;
      Alarmingly, the number of pancreatic cancer cases is constantly rising and pancreatic cancer&#xD;
      will be the second most frequent cause of cancer related death by 2030.&#xD;
&#xD;
      Accordingly, novel therapeutic strategies for patients with pancreatic cancer are desperately&#xD;
      needed.&#xD;
&#xD;
      Recently, the combination of gemcitabine and nab-paclitaxel proofed to be superior when&#xD;
      compared to single agent gemcitabine (overall survival [OS] 8.7 months in the&#xD;
      nab-paclitaxel/gemcitabine group versus 6.6 months in the gemcitabine group; hazard ratio for&#xD;
      death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P&lt;0.001). Consequently, this&#xD;
      combination therapy is now regarded as a novel treatment option for patient with metastatic&#xD;
      pancreatic cancer and should therefore serve as a backbone for future clinical studies.&#xD;
&#xD;
      Preclinical studies suggest a significant role for ErbB signaling in the pathogenesis of&#xD;
      pancreatic cancer. Accordingly, targeting the family of ErbB receptor tyrosine kinases seems&#xD;
      to be a viable option to improve the outcome of patients with pancreatic cancer. Addition of&#xD;
      the selective reversible EGFR tyrosine kinase inhibitor erlotinib to gemcitabine&#xD;
      significantly improved progression-free survival and overall survival in metastatic&#xD;
      pancreatic cancer patients. However, the effect on median survival time in absolute values&#xD;
      between the two arms (erlotinib and gemcitabine versus gemcitabine alone) accounted for less&#xD;
      than a half month.&#xD;
&#xD;
      Afatinib is a selective, potent and irreversible ErbB family blocker. Unlike erlotinib,&#xD;
      afatinib covalently binds to and irreversibly blocks signalling from all homo- and&#xD;
      heterodimers formed by the ErbB family members EGFR (ErbB1), HER2 (ErbB2), ErbB3 and ErbB4.&#xD;
      Afatinib is applied orally once daily. Preclinical studies suggest that application of&#xD;
      afatinib should result in greater efficacy against tumor growth than application of&#xD;
      erlotinib.&#xD;
&#xD;
      Afatinib as monotherapy has a marketing authorization for the treatment of locally advanced&#xD;
      or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation/mutations for&#xD;
      daily doses up to 50 mg once daily. In a Phase I trial for safety and tolerability of&#xD;
      afatinib in combination with gemcitabine in patients with advanced solid tumors the maximum&#xD;
      tolerated dose (MTD) was 40 mg afatinib (given continuously once daily) plus 1000 mg/m2&#xD;
      gemcitabine on D1 and D8 of a 21-day cycle, with no dose-limiting toxicity in the respective&#xD;
      cohort. Accordingly, in another current Phase II trial of the sponsor for treatment of&#xD;
      metastatic pancreatic cancer the dose of 40 mg continuously orally once daily given afatinib&#xD;
      in combination with 1000 mg/m2 gemcitabine given on Day1, Day 8, and Day 15 of a 28-day cycle&#xD;
      against monotherapy with gemcitabine 1000 mg/m2 is used.&#xD;
&#xD;
      The investigators hypothesize that addition of afatinib to gemcitabine/nab-paclitaxel might&#xD;
      result in better anti-tumor activity.&#xD;
&#xD;
      Accordingly, the aim of this trial is to establish the MTD for afatinib in combination with&#xD;
      gemcitabine/nab-paclitaxel in order to proceed into Phase II trials.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>September 2016</start_date>
  <completion_date type="Anticipated">June 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>MTD of afatinib in combination with gemcitabine/nab-paclitaxel</measure>
    <time_frame>28 days after the first dose of chemotherapy</time_frame>
    <description>Completion of the first cycle of chemotherapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>RECIST measurements of target lesions (in cm/inches)</measure>
    <time_frame>18 months</time_frame>
    <description>Objective Response Rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (in months)</measure>
    <time_frame>18 months</time_frame>
    <description>PFS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (in months)</measure>
    <time_frame>18 months</time_frame>
    <description>OS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>18 months</time_frame>
    <description>Type, incidence, and severity of adverse events according to NCI CTCAE version 4.03. Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Metastatic Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Afatinib 40Mg Tab, Gemzar, Abraxane +1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Level +1 Afatinib 40 mg Nab-paclitaxel 125 mg/m2 BSA Gemcitabine 1000 mg/m2 BSA</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Afatinib 30Mg Tab, Gemzar, Abraxane 0</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Level 0 Afatinib 30 mg Nab-paclitaxel 125 mg/m2 BSA Gemcitabine 1000 mg/m2 BSA</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Afatinib 30Mg Tab, Gemzar, Abraxane -1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Level -1 Afatinib 30 mg Nab-paclitaxel 100 mg/m2 BSA Gemcitabine 800 mg/m2 BSA</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Afatinib 30Mg Tab, Gemzar, Abraxane -2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Level -2 Afatinib 30 mg Nab-paclitaxel 75 mg/m2 BSA Gemcitabine 600 mg/m2 BSA</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Afatinib 30Mg Tab</intervention_name>
    <description>Study Drug</description>
    <arm_group_label>Afatinib 30Mg Tab, Gemzar, Abraxane -1</arm_group_label>
    <arm_group_label>Afatinib 30Mg Tab, Gemzar, Abraxane -2</arm_group_label>
    <arm_group_label>Afatinib 30Mg Tab, Gemzar, Abraxane 0</arm_group_label>
    <other_name>Giotrif</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Afatinib 40Mg Tab</intervention_name>
    <description>Study Drug</description>
    <arm_group_label>Afatinib 40Mg Tab, Gemzar, Abraxane +1</arm_group_label>
    <other_name>Giotrif</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemzar</intervention_name>
    <description>Chemotherapy Backbone</description>
    <arm_group_label>Afatinib 30Mg Tab, Gemzar, Abraxane -1</arm_group_label>
    <arm_group_label>Afatinib 30Mg Tab, Gemzar, Abraxane -2</arm_group_label>
    <arm_group_label>Afatinib 30Mg Tab, Gemzar, Abraxane 0</arm_group_label>
    <arm_group_label>Afatinib 40Mg Tab, Gemzar, Abraxane +1</arm_group_label>
    <other_name>Gemcitabine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abraxane</intervention_name>
    <description>Chemotherapy Backbone</description>
    <arm_group_label>Afatinib 30Mg Tab, Gemzar, Abraxane -1</arm_group_label>
    <arm_group_label>Afatinib 30Mg Tab, Gemzar, Abraxane -2</arm_group_label>
    <arm_group_label>Afatinib 30Mg Tab, Gemzar, Abraxane 0</arm_group_label>
    <arm_group_label>Afatinib 40Mg Tab, Gemzar, Abraxane +1</arm_group_label>
    <other_name>nab-Paclitaxel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult patients ≥ 18 years of age and ≤ 75 years&#xD;
&#xD;
          2. Histologically (not cytologically) confirmed diagnosis of metastatic pancreatic ductal&#xD;
             adenocarcinoma (PDAC) [Stage IV according to UICC TNM edition 7 of 2009: each T, each&#xD;
             N, M1]&#xD;
&#xD;
          3. No option for surgical resection or radiation in curative intent&#xD;
&#xD;
          4. At least one unidimensionally measurable tumor lesion (according to RECIST 1.1)&#xD;
&#xD;
          5. ECOG performance status 0 - 1&#xD;
&#xD;
          6. Life expectancy at least 3 months&#xD;
&#xD;
          7. Adequate hepatic, renal and bone marrow function, defined as:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1.5x109/L&#xD;
&#xD;
               -  Haemoglobin ≥ 9 g/dL 9&#xD;
&#xD;
               -  Thrombocytes ≥100x10/L&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5xULN.&#xD;
&#xD;
                    -  Patients with a biliary stent may be included provided that bilirubin level&#xD;
                       after stent insertion decreased to ≤ 1.5 x ULN and there is no cholangitis.&#xD;
&#xD;
               -  AST/GOT and/or ALT/GPT ≤ 2.5 x ULN or in case of liver metastasis ≤ 5 x ULN)&#xD;
&#xD;
               -  Serum creatinine within normal limits or creatinine clearance ≥60 mL/min/1.73 m2&#xD;
                  as calculated by CKD- EPI formula for patients with serum creatinine levels above&#xD;
                  or below the institutional normal value.&#xD;
&#xD;
          8. Acceptable coagulation studies defined as prothrombin time (or INR) and PTT ≤ 1.5 x&#xD;
             ULN&#xD;
&#xD;
          9. Stable/decreasing pain symptoms under pain medication or no pain within the last 2&#xD;
             weeks before first application of study medication (as reported and assessed by the&#xD;
             patient).&#xD;
&#xD;
         10. Females of childbearing potential (FCBP) must have a negative highly sensitive serum&#xD;
             pregnancy test within 7 days of the first application of study treatment and they must&#xD;
             agree to undergo a further pregnancy tests at monthly intervals and at the end of&#xD;
             treatment visit and FCBP must either agree to use and be able to take highly effective&#xD;
             contraceptive birth control methods (Pearl Index &lt; 1) or agree to practice complete&#xD;
             abstinence from heterosexual intercourse during the course of the study and for at&#xD;
             least 1 month after last application of study treatment. A female subject following&#xD;
             menarche is considered to be of childbearing potential unless she is naturally&#xD;
             amenorrhoeic for ≥ 1 year without an alternative medical reason, or unless she is&#xD;
             permanently sterile.&#xD;
&#xD;
         11. Males must agree to use condoms during the course of the trial and for at least 6&#xD;
             months after last administration of study drugs or practice complete abstinence from&#xD;
             heterosexual intercourse.&#xD;
&#xD;
         12. Signed and dated informed consent before the start of any specific protocol procedures&#xD;
&#xD;
         13. Patient's legal capacity to consent to study participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Locally advanced PDAC without metastasis&#xD;
&#xD;
          2. Evidence of ascites&#xD;
&#xD;
          3. Known metastatic disease to the brain. Brain imaging is required in symptomatic&#xD;
             patients to rule out brain metastases, but is not required in asymptomatic patients.&#xD;
&#xD;
          4. Previous palliative chemotherapy or other palliative systemic tumor therapy for&#xD;
             metastatic disease of PDAC&#xD;
&#xD;
          5. Previous gemcitabine treatment with exception of gemcitabine treatment applied as&#xD;
             monotherapy in the adjuvant setting (after potential curative R0 or R1 resection) and&#xD;
             if the adjuvant single-agent gemcitabine chemotherapy was terminated at least 6 months&#xD;
             before study entry&#xD;
&#xD;
          6. Previous radiotherapy of PDAC&#xD;
&#xD;
          7. Previous ErbB family directed therapy for PDAC (e. g. erlotinib, cetuximab,&#xD;
             trastuzumab, lapatinib)&#xD;
&#xD;
          8. Any major surgery within the last 4 weeks before study entry&#xD;
&#xD;
          9. Clinical significant decrease in performance status within 2 weeks of intended first&#xD;
             application of study medication (by medical history)&#xD;
&#xD;
         10. Severe tumor-related cachexia and/or known weight loss &gt;15% within one month before&#xD;
             study enrollment&#xD;
&#xD;
         11. Pre-existing polyneuropathy ≥ grade 2 according to CTCAE version 4.03&#xD;
&#xD;
         12. LDH &gt;2.5xULN&#xD;
&#xD;
         13. Significant (≥ 20%) decrease in serum albumin levels within 2 weeks of intended first&#xD;
             application of study medication (by medical history)&#xD;
&#xD;
         14. Gastrointestinal disorders that might interfere with the absorption of the study drug&#xD;
             and gastrointestinal disorders with diarrhoea as a major symptom (e.g. Crohn's&#xD;
             disease, malabsorption), and chronic diarrhoea of any aetiology CTCAE version 4.03&#xD;
             grade ≥ 2&#xD;
&#xD;
         15. Medical history of interstitial lung disease (ILD) or pulmonary fibrosis or severe&#xD;
             COPD&#xD;
&#xD;
         16. Liver cirrhosis Child-Pugh other than class A&#xD;
&#xD;
         17. Known coagulopathy or bleeding disorder&#xD;
&#xD;
         18. History of connective tissue disorders (e.g. lupus, scleroderma,arteritis nods)&#xD;
&#xD;
         19. Any other severe concomitant disease or disorder, which could influence patient's&#xD;
             ability to participate in the study and his/her safety during the study or interfere&#xD;
             with interpretation of study results e.g. active infection, uncontrolled hypertension,&#xD;
             clinically significant cardiovascular disease e.g. cerebral vascular accident (≤ 6&#xD;
             months before study start), myocardial infarction (≤ 6 months before study start),&#xD;
             unstable angina, heart failure ≥ NYHA functional classification system grade 2, severe&#xD;
             cardiac arrhythmia requiring medication, metabolic dysfunction, severe renal disorder.&#xD;
&#xD;
         20. Any other malignancies than PDAC within the last 5 years before study start, except&#xD;
             for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin&#xD;
             cancer&#xD;
&#xD;
         21. Hypersensitivity to afatinib, nab-paclitaxel, or gemcitabine or to any of the&#xD;
             excipients or to compounds with similar chemical or biologic composition&#xD;
&#xD;
         22. Continuing abuse of alcohol,drugs,or medical drugs&#xD;
&#xD;
         23. Pregnant or breast-feeding females or FCBPs unable to either perform highly effective&#xD;
             contraceptive measures or practice complete abstinence from heterosexual intercourse&#xD;
&#xD;
         24. Current or recent (within 4 weeks prior to first application of study treatment)&#xD;
             treatment with an investigational drug or participation in an investigational clinical&#xD;
             trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Volker Heinemann, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Munich - Klinikum Großhadern</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ludwig-Maximilians - University of Munich</name>
      <address>
        <city>Munich</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>September 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>August 9, 2018</last_update_submitted>
  <last_update_submitted_qc>August 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ludwig-Maximilians - University of Munich</investigator_affiliation>
    <investigator_full_name>PD Dr. med. Volker Heinemann</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Palliative Chemotherapy</keyword>
  <keyword>Afatinib</keyword>
  <keyword>Gemcitabine</keyword>
  <keyword>nab-paclitaxel</keyword>
  <keyword>pancreatic cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
    <mesh_term>Afatinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02975141
org study id: 2015-004065-86
nct id: NCT02975141
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This study sets out to determine the maximum tolerated dose (MTD) of afatinib in combination
      with gemcitabine/nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma.
      The identified MTD will serve as recommended phase II dose (RP2D).
Pancreatic ductal adenocarcinoma (PDAC) remains an almost uniformly lethal disease. Although
      there has been significant progress in understanding of the underlying molecular biology of
      pancreatic cancer, this progress has not translated into substantially better treatments.
      Alarmingly, the number of pancreatic cancer cases is constantly rising and pancreatic cancer
      will be the second most frequent cause of cancer related death by 2030.

      Accordingly, novel therapeutic strategies for patients with pancreatic cancer are desperately
      needed.

      Recently, the combination of gemcitabine and nab-paclitaxel proofed to be superior when
      compared to single agent gemcitabine (overall survival [OS] 8.7 months in the
      nab-paclitaxel/gemcitabine group versus 6.6 months in the gemcitabine group; hazard ratio for
      death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P<0.001). Consequently, this
      combination therapy is now regarded as a novel treatment option for patient with metastatic
      pancreatic cancer and should therefore serve as a backbone for future clinical studies.

      Preclinical studies suggest a significant role for ErbB signaling in the pathogenesis of
      pancreatic cancer. Accordingly, targeting the family of ErbB receptor tyrosine kinases seems
      to be a viable option to improve the outcome of patients with pancreatic cancer. Addition of
      the selective reversible EGFR tyrosine kinase inhibitor erlotinib to gemcitabine
      significantly improved progression-free survival and overall survival in metastatic
      pancreatic cancer patients. However, the effect on median survival time in absolute values
      between the two arms (erlotinib and gemcitabine versus gemcitabine alone) accounted for less
      than a half month.

      Afatinib is a selective, potent and irreversible ErbB family blocker. Unlike erlotinib,
      afatinib covalently binds to and irreversibly blocks signalling from all homo- and
      heterodimers formed by the ErbB family members EGFR (ErbB1), HER2 (ErbB2), ErbB3 and ErbB4.
      Afatinib is applied orally once daily. Preclinical studies suggest that application of
      afatinib should result in greater efficacy against tumor growth than application of
      erlotinib.

      Afatinib as monotherapy has a marketing authorization for the treatment of locally advanced
      or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation/mutations for
      daily doses up to 50 mg once daily. In a Phase I trial for safety and tolerability of
      afatinib in combination with gemcitabine in patients with advanced solid tumors the maximum
      tolerated dose (MTD) was 40 mg afatinib (given continuously once daily) plus 1000 mg/m2
      gemcitabine on D1 and D8 of a 21-day cycle, with no dose-limiting toxicity in the respective
      cohort. Accordingly, in another current Phase II trial of the sponsor for treatment of
      metastatic pancreatic cancer the dose of 40 mg continuously orally once daily given afatinib
      in combination with 1000 mg/m2 gemcitabine given on Day1, Day 8, and Day 15 of a 28-day cycle
      against monotherapy with gemcitabine 1000 mg/m2 is used.

      The investigators hypothesize that addition of afatinib to gemcitabine/nab-paclitaxel might
      result in better anti-tumor activity.

      Accordingly, the aim of this trial is to establish the MTD for afatinib in combination with
      gemcitabine/nab-paclitaxel in order to proceed into Phase II trials.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: MTD of afatinib in combination with gemcitabine/nab-paclitaxel
time frame: 28 days after the first dose of chemotherapy
description: Completion of the first cycle of chemotherapy
measure: RECIST measurements of target lesions (in cm/inches)
time frame: 18 months
description: Objective Response Rate
measure: Progression free survival (in months)
time frame: 18 months
description: PFS
measure: Overall survival (in months)
time frame: 18 months
description: OS
measure: Incidence of Treatment-Emergent Adverse Events
time frame: 18 months
description: Type, incidence, and severity of adverse events according to NCI CTCAE version 4.03. Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment.
arm group label: Afatinib 40Mg Tab, Gemzar, Abraxane +1
arm group type: Experimental
description: Dose Level +1 Afatinib 40 mg Nab-paclitaxel 125 mg/m2 BSA Gemcitabine 1000 mg/m2 BSA
arm group label: Afatinib 30Mg Tab, Gemzar, Abraxane 0
arm group type: Experimental
description: Dose Level 0 Afatinib 30 mg Nab-paclitaxel 125 mg/m2 BSA Gemcitabine 1000 mg/m2 BSA
arm group label: Afatinib 30Mg Tab, Gemzar, Abraxane -1
arm group type: Experimental
description: Dose Level -1 Afatinib 30 mg Nab-paclitaxel 100 mg/m2 BSA Gemcitabine 800 mg/m2 BSA
arm group label: Afatinib 30Mg Tab, Gemzar, Abraxane -2
arm group type: Experimental
description: Dose Level -2 Afatinib 30 mg Nab-paclitaxel 75 mg/m2 BSA Gemcitabine 600 mg/m2 BSA
intervention type: Drug
intervention name: Afatinib 30Mg Tab
description: Study Drug
arm group label: Afatinib 30Mg Tab, Gemzar, Abraxane -1
arm group label: Afatinib 30Mg Tab, Gemzar, Abraxane -2
arm group label: Afatinib 30Mg Tab, Gemzar, Abraxane 0
other name: Giotrif
intervention type: Drug
intervention name: Afatinib 40Mg Tab
description: Study Drug
arm group label: Afatinib 40Mg Tab, Gemzar, Abraxane +1
other name: Giotrif
intervention type: Drug
intervention name: Gemzar
description: Chemotherapy Backbone
arm group label: Afatinib 30Mg Tab, Gemzar, Abraxane -1
arm group label: Afatinib 30Mg Tab, Gemzar, Abraxane -2
arm group label: Afatinib 30Mg Tab, Gemzar, Abraxane 0
arm group label: Afatinib 40Mg Tab, Gemzar, Abraxane +1
other name: Gemcitabine
intervention type: Drug
intervention name: Abraxane
description: Chemotherapy Backbone
arm group label: Afatinib 30Mg Tab, Gemzar, Abraxane -1
arm group label: Afatinib 30Mg Tab, Gemzar, Abraxane -2
arm group label: Afatinib 30Mg Tab, Gemzar, Abraxane 0
arm group label: Afatinib 40Mg Tab, Gemzar, Abraxane +1
other name: nab-Paclitaxel
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Volker Heinemann, Professor
role: Principal Investigator
affiliation: University of Munich - Klinikum Großhadern
facility: 
country: Germany
responsible party type: Sponsor-Investigator
investigator affiliation: Ludwig-Maximilians - University of Munich
investigator full name: PD Dr. med. Volker Heinemann
investigator title: Professor of Medicine
mesh term: Pancreatic Neoplasms
mesh term: Paclitaxel
mesh term: Gemcitabine
mesh term: Albumin-Bound Paclitaxel
mesh term: Afatinib
sharing ipd: No