Investigation of Potential Drug-drug Interaction of Volasertib With Itraconazole in Patients With Various Tumours
Condition: Neoplasms
Intervention: volasertib; itraconazole
Intervention description: Solution for infusion; capsules
Intervention MeSH terms: Itraconazole
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The primary objective of the present study is to investigate the influence of
      co-administration of itraconazole and volasertib on the pharmacokinetic profile of volasertib
      without co-administration of itraconazole. Secondary objectives are to investigate safety,
      tolerability and preliminary therapeutic effects following intravenous administration of
      volasertib.
    

Eligibility criteria:

        Inclusion criteria:

          1. Patients with histologically or cytologically confirmed diagnosis of advanced, non
             resectable and / or metastatic solid tumour, for whom conventional treatment has
             failed, or for whom no therapy of proven efficacy exists, or who are not amenable to
             established forms of treatment based on the investigator's assessment

          2. Male or female

          3. Age =>18 and =<70 years

          4. Eastern Cooperative Oncology Group (ECOG) performance score =< 2

          5. Recovery from Common Terminology Criteria for Adverse Events (CTCAE) Grade >= 2
             therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapy
             (except alopecia)

        Exclusion criteria:

          1. Serious concomitant non-oncological disease considered by the investigator to be
             incompatible with the protocol

          2. Active infectious disease

          3. Viral hepatitis, HIV infection

          4. Clinical evidence of active brain metastasis or leptomeningeal disease during the past
             6 months

          5. Second malignancy currently requiring active therapy (except for hormonal /
             antihormonal treatment e.g. in prostate or breast cancer)

          6. Absolute neutrophil count less than 1,500/mm3

          7. Platelet count less than 100,000/mm3

          8. Total bilirubin greater than 1.5 mg/dL (> 26 µmol/L, SI unit equivalent)

          9. Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater
             than 2.5 times the upper limit of normal (if related to liver metastases greater than
             five times the upper limit of normal)

         10. Serum creatinine greater than 2x upper limit of normal (ULN)

         11. QTcF prolongation > 470 ms or QT prolongation deemed clinically relevant by the
             investigator (e.g., congenital long QT syndrome).The QTcF will be calculated as the
             mean of the 3 ECGs taken at screening

         12. Female patients with childbearing potential and unwilling to use a medically
             acceptable method of contraception during the trial and for at least six months after
             end of active therapy. Woman of childbearing potential (premenopausal female) is
             defined as the female who is not surgically sterilised by hysterectomy or bilateral
             tubal ligation or post-menopausal for at least 12 months.

         13. Treatment with other investigational drugs or participation in another clinical trial
             within the past four weeks prior to start of therapy or concomitantly with this trial

         14. Chemo-, radio- immuno-, or molecular-targeted cancer-therapy within the past four
             weeks prior to start of therapy or concomitantly with this trial. This restriction
             does not apply to steroids, bisphosphonates hormonal / antihormonal treatment (e.g. in
             prostate or breast cancer).

         15. Alcohol abuse more than an average 3 units of alcoholic beverages per day or more than
             21 units per week (1 unit equals 0.5 pint [285 mL] of beer or lager, 1 glass [125 mL]
             of wine, 25 mL shot of 40% spirit) or drug abuse

         16. Life expectancy less than 12 weeks

         17. Potent CYP 3A4 and P-glycoprotein inhibitors other than the study drug or inducers
             between one week prior to first drug administration or expected treatment with a
             respective drug until the last PK sample is collected

               1. Strong CYP 3A4 inhibitors: atazanavir, clarithromycin, indinavir, itraconazole
                  (other then study drug), ketoconazole, nefazodone, nelfinavir, ritonavir,
                  saquinavir, telithromycin

               2. CYP 3A4 inducers: carbamazepine, rifampicin

               3. P-gp inhibitors: cyclosporine, erythromycin, itraconazole (other then study
                  drug), ketoconazole, quinidine, phenobarbital salt with quinidine, ritonavir,
                  valspodar, verapamil

               4. P-gp inducers: hypericum perforatum, rifampicin