NeoplasmsPhase 1NCT01772563

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

A Phase 1 study testing volasertib and itraconazole in people with Neoplasms, run by Boehringer Ingelheim at 2 sites in Hungary.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Neoplasms
What is being tested?: volasertib and itraconazole
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 28 participants
Where: 2 sitesHungary
Study dates: 4 Feb 2013to 22 Apr 2021
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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
Male or female
Age =>18 and =<70 years
Eastern Cooperative Oncology Group (ECOG) performance score =< 2
Recovery from Common Terminology Criteria for Adverse Events (CTCAE) Grade >= 2 therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapy (except alopecia)

Who cannot join

Serious concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
Active infectious disease
Viral hepatitis, HIV infection
Clinical evidence of active brain metastasis or leptomeningeal disease during the past 6 months
Second malignancy currently requiring active therapy (except for hormonal / antihormonal treatment e.g. in prostate or breast cancer)
Absolute neutrophil count less than 1,500/mm3

Show all 21Show fewer

Platelet count less than 100,000/mm3
Total bilirubin greater than 1.5 mg/dL (> 26 µmol/L, SI unit equivalent)
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)
Serum creatinine greater than 2x upper limit of normal (ULN)
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
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.
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
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).
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
Life expectancy less than 12 weeks
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
Strong CYP 3A4 inhibitors: atazanavir, clarithromycin, indinavir, itraconazole (other then study drug), ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin
CYP 3A4 inducers: carbamazepine, rifampicin
P-gp inhibitors: cyclosporine, erythromycin, itraconazole (other then study drug), ketoconazole, quinidine, phenobarbital salt with quinidine, ritonavir, valspodar, verapamil
P-gp inducers: hypericum perforatum, rifampicin

Trial locations and contacts

2 sites in 1 country.

Hungary2 sites

PRA Hungary Ltd., Phase I. Clinical Pharmacology Unit
Budapest, 1077
National Institute of Oncology
Budapest, 1122

Other trials in Hungary

About this study

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

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.

Conditions: Neoplasms
Being tested: volasertib, itraconazole
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

volasertibDrug
Solution for infusion
itraconazoleDrug
Also called Orungal®
capsules

Study groups in NCT01772563
Study group	Role	What they receive
Volasertib + itraconazole then volasertib	Experimental	Administration of volasertib in combination with itraconazole (Cycle 1) and afterwards alone (Cycle 2 and beyond). Receives: Drug: volasertib; Drug: itraconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Last Quantifiable Drug Plasma Concentration After Dose Administration (AUC0-tz) of Volasertib and Its Metabolite CD 10899
Area under the plasma concentration-time curve over the time interval from zero to the last quantifiable drug plasma concentration after dose administration (AUC0-tz) of volasertib and its metabolite CD 10899 is reported.
Measured: 30 minutes before volasertib administration and 1 hour (h), 1.75h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 72h, 168h, 336h, 504 h after volasertib administration on Day 1 of Cycle 1 (Volasertib+ Itraconazole) and of Cycle 2 (Volasertib).
Maximum Measured Concentration of Volasertib and Its Metabolite CD 10899 in Plasma (Cmax)
Maximum measured concentration of the analyte (volasertib and its metabolite CD 10899) in plasma (Cmax) is reported.
Measured: 30 minutes before volasertib administration and 1 hour (h), 1.75h, 4h, 6h, 8h, 12h, 24, 36h, 48h, 72h, 168h, 336h, 504 h after volasertib administration on Day 1 of Cycle 1 (Volasertib+ Itraconazole) and of Cycle 2 (Volasertib).

Secondary outcomes (1)

Area Under the Plasma Concentration-time Curve Over the Time Interval From 0 to Infinity (AUC0-∞) of Volasertib and Its Metabolite CD 10899
Area under the plasma concentration-time curve over the time interval from 0 to infinity (AUC0-∞) of volasertib and its metabolite CD 10899 is reported.
Measured: 30 minutes before volasertib administration and 1 hour (h), 1.75h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 72h, 168h, 336h, 504 h after volasertib administration on Day 1 of Cycle 1 (Volasertib+ Itraconazole) and of Cycle 2 (Volasertib).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Feb 201322 Apr 2021

First posted21 Jan 2013 (estimated)
Study start4 Feb 2013
Primary completion30 May 2014
Study completion22 Apr 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for NeoplasmsStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01772563
Sponsor's protocol ID: 1230.24
Other IDs: 2011-002367-23
Status last verified: Nov 2022
First submitted: 17 Jan 2013
Last updated: 1 Sep 2023
Results posted: Yes, on ClinicalTrials.gov
Individual data sharing: No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

Publications

Lang I, Liu D, Fritsch H, Taube T, Chizhikov E, Liptai B. Potential Drug-Drug Interactions with Combination Volasertib + Itraconazole: A Phase I, Fixed-sequence Study in Patients with Solid Tumors. Clin Ther. 2020 Nov;42(11):2214-2224. doi: 10.1016/j.clinthera.2020.09.015. Epub 2020 Nov 1.
PubMed 33139055

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Neoplasms trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01772563
Acronym / sponsor ID: 1230.24
Conditions: Neoplasms
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 4 Feb 2013 (actual)
Primary completion: 30 May 2014 (actual)
Study completion: 22 Apr 2021 (actual)
First posted: 21 Jan 2013 (estimated)
Results: Posted 1 Sep 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Volasertib + itraconazole then volasertib	Experimental	Drug: volasertib, Drug: itraconazoleAdministration of volasertib in combination with itraconazole (Cycle 1) and afterwards alone (Cycle 2 and beyond).

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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
Male or female
Age =>18 and =<70 years
Eastern Cooperative Oncology Group (ECOG) performance score =< 2
Recovery from Common Terminology Criteria for Adverse Events (CTCAE) Grade >= 2 therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapy (except alopecia)

Key exclusion criteria (21 listed)

Serious concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
Active infectious disease
Viral hepatitis, HIV infection
Clinical evidence of active brain metastasis or leptomeningeal disease during the past 6 months
Second malignancy currently requiring active therapy (except for hormonal / antihormonal treatment e.g. in prostate or breast cancer)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
volasertibSolution for infusion	Drug	Volasertib + itraconazole then volasertib
itraconazoleAlso: Orungal®capsules	Drug	Volasertib + itraconazole then volasertib

Primary outcome

Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Last Quantifiable Drug Plasma Concentration After Dose Administration (AUC0-tz) of Volasertib and Its Metabolite CD 10899
Time frame: 30 minutes before volasertib administration and 1 hour (h), 1.75h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 72h, 168h, 336h, 504 h after volasertib administration on Day 1 of Cycle 1 (Volasertib+ Itraconazole) and of Cycle 2 (Volasertib).
Area under the plasma concentration-time curve over the time interval from zero to the last quantifiable drug plasma concentration after dose administration (AUC0-tz) of volasertib and its metabolite CD 10899 is reported.
Maximum Measured Concentration of Volasertib and Its Metabolite CD 10899 in Plasma (Cmax)
Time frame: 30 minutes before volasertib administration and 1 hour (h), 1.75h, 4h, 6h, 8h, 12h, 24, 36h, 48h, 72h, 168h, 336h, 504 h after volasertib administration on Day 1 of Cycle 1 (Volasertib+ Itraconazole) and of Cycle 2 (Volasertib).
Maximum measured concentration of the analyte (volasertib and its metabolite CD 10899) in plasma (Cmax) is reported.

1 secondary outcome

Area Under the Plasma Concentration-time Curve Over the Time Interval From 0 to Infinity (AUC0-∞) of Volasertib and Its Metabolite CD 10899
Time frame: 30 minutes before volasertib administration and 1 hour (h), 1.75h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 72h, 168h, 336h, 504 h after volasertib administration on Day 1 of Cycle 1 (Volasertib+ Itraconazole) and of Cycle 2 (Volasertib).

Results and safety

Results posted to the registry on 1 Sep 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Volasertib + Itraconazole Then Volasertib	28	24

Primary outcome: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Last Quantifiable Drug Plasma Concentration After Dose Administration (AUC0-tz) of Volasertib and Its Metabolite CD 10899

Time frame: 30 minutes before volasertib administration and 1 hour (h), 1.75h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 72h, 168h, 336h, 504 h after volasertib administration on Day 1 of Cycle 1 (Volasertib+ Itraconazole) and of Cycle 2 (Volasertib).. Geometric mean (Geometric Coefficient of Variation). Unit: nanogram*hour/milliliter (ng*h/mL)

Measure	Volasertib+ Itraconazole (Cycle 1) n = 21	Volasertib (Cycle 2) n = 21
volasertib	6690 (36.0)	7140 (55.6)
CD 10899	855 (63.8)	1130 (58.0)

Volasertib+ Itraconazole (Cycle 1) vs Volasertib (Cycle 2): Geometric mean ratio (GMR) [%]: 93.63 (90% CI 82.07 to 106.81)
Volasertib+ Itraconazole (Cycle 1) vs Volasertib (Cycle 2): Geometric mean ratio (GMR) [%]: 75.77 (90% CI 67.830 to 84.632)

Population analysed: Primary pharmacokinetic set (pPKS) 250 mg: All patients in the treated set (TS) who were treated with volasertib 250 mg in Cycle 1 and Cycle 2 and who provided complete pharmacokinetic (PK) measures without important protocol violations.

Primary outcome: Maximum Measured Concentration of Volasertib and Its Metabolite CD 10899 in Plasma (Cmax)

Time frame: 30 minutes before volasertib administration and 1 hour (h), 1.75h, 4h, 6h, 8h, 12h, 24, 36h, 48h, 72h, 168h, 336h, 504 h after volasertib administration on Day 1 of Cycle 1 (Volasertib+ Itraconazole) and of Cycle 2 (Volasertib).. Geometric mean (Geometric Coefficient of Variation). Unit: nanogram/milliliter (ng/mL)

Measure	Volasertib+ Itraconazole (Cycle 1) n = 21	Volasertib (Cycle 2) n = 21
volasertib	328 (46.0)	414 (53.1)
CD 10899	4.51 (78.4)	7.10 (63.4)

Volasertib+ Itraconazole (Cycle 1) vs Volasertib (Cycle 2): Geometric mean ratio (GMR) [%]: 79.40 (90% CI 64.896 to 97.137)
Volasertib+ Itraconazole (Cycle 1) vs Volasertib (Cycle 2): Geometric mean ratio (GMR) [%]: 63.48 (90% CI 55.372 to 72.775)

Population analysed: Primary pharmacokinetic set (pPKS) 250 mg: All patients in the treated set (TS) who were treated with volasertib 250 mg in Cycle 1 and Cycle 2 and who provided complete pharmacokinetic set (PK) measures without important protocol violations.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Volasertib + Itraconazole (Cycle 1) arm: From start of itraconazole administration until 21 days after the administration of volasertib, up to 24 days. Monotherapy Volasertib (Cycle>=2): From start of monotherapy with volasertib (Day 1 of Cycle 2) until 21 days after the last administration of volasertib, up to 2712 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Volasertib + Itraconazole (Cycle 1)	12 of 28 (42.9%)	21 of 28 (75%)	0 of 28
Monotherapy Volasertib (Cycle>=2)	11 of 24 (45.8%)	21 of 24 (87.5%)	1 of 24

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33139055Lang I, Liu D, Fritsch H, Taube T, Chizhikov E, Liptai B. Potential Drug-Drug Interactions with Combination Volasertib + Itraconazole: A Phase I, Fixed-sequence Study in Patients with Solid Tumors. Clin Ther. 2020 Nov;42(11):2214-2224. doi: 10.1016/j.clinthera.2020.09.015. Epub 2020 Nov 1.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing volasertib and itraconazole in people with Neoplasms, run by Boehringer Ingelheim at 2 sites in Hungary.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Last Quantifiable Drug Plasma Concentration After Dose Administration (AUC0-tz) of Volasertib and Its Metabolite CD 10899 (time frame: 30 minutes before volasertib administration and 1 hour (h), 1.75h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 72h, 168h, 336h, 504 h after volasertib administration on Day 1 of Cycle 1 (Volasertib+ Itraconazole) and of Cycle 2 (Volasertib).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01772563, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2023.