Investigation of Potential Drug-drug Interaction of Volasertib With Itraconazole in Patients With Various Tumours

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01772563
First received: January 17, 2013
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Neoplasms
Drug: volasertib
Drug: itraconazole
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: An Open-label Fixed Sequence Trial to Investigate the Potential Drug-drug Interaction of Intravenous Volasertib Co-administered With a P-gp and CYP3A4 Inhibitor (Itraconazole p.o.) in Patients With Various Solid Tumours

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • area under the plasma concentration-time curve over the time interval from zero to 336 hours (AUC0-tz) [ Time Frame: up to 336 hours ] [ Designated as safety issue: No ]
  • maximum measured plasma concentration (Cmax) [ Time Frame: up to 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC0-infinity) [ Time Frame: up to 6 weeks ] [ Designated as safety issue: No ]
  • number of patients with adverse events [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
  • number of participants with significant abnormalities in electrocardiogram results [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
  • occurance of significant changes from baseline laboratory measurements [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 28
Study Start Date: February 2013
Estimated Study Completion Date: March 2015
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: volasertib + itraconazole
administration of volasertib alone and in combination with itraconazole
Drug: volasertib
cycle in 21 days
Drug: itraconazole
over 18 days

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01772563

Locations
Hungary
1230.24.36001 Boehringer Ingelheim Investigational Site
Budapest, Hungary
1230.24.36002 Boehringer Ingelheim Investigational Site
Budapest, Hungary
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01772563     History of Changes
Other Study ID Numbers: 1230.24, 2011-002367-23
Study First Received: January 17, 2013
Last Updated: August 6, 2014
Health Authority: Hungary: National Institute of Pharmacy
United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Itraconazole
Hydroxyitraconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014