An Open Label Phase I Dose Escalation Trial of Intravenous BI 6727 (Volasertib)in Combination With Oral BIBW 2992 (Afatinib) in Patients With Advanced Solid Tumours
Condition: Neoplasms
Intervention: BI 6727 + BIBW 2992
Intervention description: BI 6727 administered i.v. every 21 days + BIBW 2992 given orally once a day
Intervention MeSH terms: Afatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of the current study is to investigate the Maximum Tolerated Dose (MTD)
      in terms of safety and tolerability of the combination of BI 6727 with BIBW 2992, in patients
      with advanced or metastatic solid tumours. Dosages of both BI 6727 and BIBW 2992 will be
      varied to establish the MTD of the combination. Two combination treatment schedules will be
      tested, the MTD of each combination will be determined.

      Secondary objectives are the exploration of pharmacokinetics, overall safety and preliminary
      efficacy.
    

Eligibility criteria:

        Inclusion criteria:

          -  Patients with histologically or cytologically confirmed diagnosis of advanced, non
             resectable and/or metastatic, relapsed or refractory solid tumours not amenable to
             standard therapy and for whom no therapy of proven efficacy exists

          -  Eastern Cooperative Oncology Group performance score 0 - 2

          -  Recovery from clinically significant toxicities from previous systemic anti-cancer
             therapies or radiotherapy

        Exclusion criteria:

          -  Serious illness, concomitant non-oncological disease or mental problem considered by
             the investigator to be incompatible with participation to the trial

          -  Known hypersensitivity to the trial drugs or their excipients

          -  Treatment with any other investigational drug or active participation in any other
             interventional trial within 28 days before first administration of trial drug(s) or
             concomitantly with this trial

          -  Major surgery or radiotherapy within 28 days before start of therapy or concomitantly
             with this trial

          -  Systemic anti-cancer therapy within 28 days before start of therapy or concomitantly
             with this trial

          -  Requirements for treatment with any of the prohibited concomitant medications

          -  Active infectious disease or known HIV I/II infection

          -  Gastrointestinal disorders that may interfere with the absorption of the study drug or
             chronic diarrhoea

          -  Active brain metastases

          -  History or presence of cardiovascular abnormalities deemed clinically relevant by the
             investigator

          -  Cardial left ventricular function with resting ejection fraction < 50%

          -  Inadequate hepatic, renal and haematologic organ function

          -  QT prolongation deemed clinically relevant by the investigator

          -  Active alcohol or drug abuse

          -  Women of childbearing potential and men who are able to father a child unwilling to
             use a medically acceptable method of contraception during the trial and 28 days
             thereafter

          -  Pregnancy or breast-feeding

          -  Patients unable to comply with the protocol

          -  Patients with known pre-existing interstitial lung disease