NeoplasmsPhase 1NCT01348347

BI 6727 (Volasertib) Monotherapy Phase I Trial in Japanese Patients With Advanced Solid Tumours

A Phase 1 study testing Volasertib, low dose, d1q3w, Volasertib, middle dose, d1q3w and Volasertib, high dose, d1q3w in people with Neoplasms, run by Boehringer Ingelheim at 1 site in Japan.

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

This open-label phase I dose escalation trial, 1230.15, is the first trial with Volasertib in Japanese advanced cancer patients. The trial will investigate the maximum tolerated dose (MTD), safety, tolerability, and preliminary efficacy of this specific polo-like kinase 1 (Plk1) inhibitor in advanced cancer patients. Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Neoplasms
What is being tested?: Volasertib, low dose, d1q3w, Volasertib, middle dose, d1q3w and Volasertib, high dose, d1q3w
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 1 siteJapan
Study dates: 25 Apr 2011to 15 May 2014
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 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients with histologically or cytologically confirmed according to the discretion of the investigator
Patients who have advanced, non-resectable and/or metastatic solid tumours according to the discretion of the investigator
Patients who have failed conventional treatment, or for whom no therapy of proved efficacy exists, or who are not amenable to established forms of treatment according to the discretion of the investigator
Age >=20 years old at the time of informed consent
Written informed consent
Life expectancy of at least 12 weeks according to the discretion of the investigator

Show all 17Show fewer

Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Recovery to Common Terminology Criteria for Adverse Events (CTCAE) grade =1 of therapy-related toxicities from previous chemo-, hormonal-, immuno-, or radiotherapy (except alopecia and hyperpigmentation)
Adequate bone marrow, renal and hepatic function;
Neutrophil count: more than 1500/mm3
Platelet count: more than 100 000/mm3
Haemoglobin: more than 9.0 g/dL
Total bilirubin: less than 1.5 times the upper limit of normal (ULN)
Aspartate amino transferase (AST): less than 2.5 × ULN
Alanine amino transferase (ALT): less than 2.5 × ULN
Serum creatinine: less than 1.5 × ULN
Patients who can be hospitalised during the first course

Who cannot join

Major surgery within 4 weeks prior to registration or the side effects/toxicities of such surgery that have not recovered to CTCAE grade =1
Known seropositivity to human immunodeficiency virus (HIV) antibody, hepatitis B antigen or hepatitis C antibody
Accumulation of coelomic fluid (e.g. pleural effusion, ascites fluid) requiring treatment during the trial (Patients are eligible if treated curatively and with no evidence of recurrence.)
Current symptomatic brain metastases or patients who require treatment of the brain metastases
Previous double cancers. Other tumours (except for non-invasive and/or non-melanomatous skin cancer, completely removed in situ carcinoma of the epithelium or mucosa) treated curatively and with no evidence of recurrence for at least 5 years prior to the initial study treatment will be eligible.
Known history of cardiac dysfunction;

Show all 19Show fewer

Correction of QT intervals according to Fridericias formula (QTc) over 470 ms
History of unstable angina pectoris within 6 months or current unstable angina pectoris
History of myocardial infarction within 6 months
Arrhythmia currently required active therapy
Previous and current cardiac failure
History of other clinically significant cardiac diseases according to the discretion of the investigator
Pregnant or breastfeeding women
Women and men who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. implants, injectables, combined oral contraceptives, some intrauterine devices, vasectomised partner, or condoms) during the trial and for at least 6 months after the end of active therapy. Women who are sexually active are premenopausal female patients. Premenopausal female patient is defined as the patient who observed menses within 12 months except for an alternative medical cause. Women who underwent an operation for sterilisation is excluded for this criteria.
Treatment with other investigational drugs within the past 4 weeks before registration or concomitantly with this trial (except for present trial drug)
Chemo-, radio-, immuno-, or molecular-targeted therapy within the past 4 weeks before registration or concomitantly with this trial. This restriction does not apply to bisphosphonates.
Patients unable to comply with the protocol according to the discretion of the investigator or sub-investigators
Current alcohol abuse or drug abuse according to the discretion of the investigator
Patients who are inappropriate for this trial by the discretion of investigator or sub-investigators (e.g. uncontrolled diabetes mellitus, evidence of serious active infection, medically significant abnormal laboratory finding, etc.)

Trial locations and contacts

1 site in 1 country.

Japan1 site

1230.15.001 National Cancer Center Hospital,
Chuo-ku, Tokyo

Other trials in Japan

About this study

Official title: An Open-label Phase I Study of Once Every Three Weeks Intravenous Treatment With BI 6727 in Japanese Patients With Advanced Solid Tumours

Conditions: Neoplasms
Being tested: Volasertib, low dose, d1q3w, Volasertib, middle dose, d1q3w, Volasertib, high dose, d1q3w
Medical subject headings: Neoplasms

What participants receive

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

Volasertib, low dose, d1q3wDrug
Patient to receive low dose of Volasertib IV
Volasertib, middle dose, d1q3wDrug
Patient to receive middle dose of Volasertib IV
Volasertib, high dose, d1q3wDrug
Patient to receive high dose of Volasertib IV

Study groups in NCT01348347
Study group	Role	What they receive
Volasertib	Experimental	Patient to receive low, middle and high doses of Volasertib IV Receives: Drug: Volasertib, low dose, d1q3w; Drug: Volasertib, middle dose, d1q3w; Drug: Volasertib, high dose, d1q3w

What is being measured

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

Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD).
The following drug-related adverse events (AE) were defined as DLT;
1. Haematological toxicities: CTCAE(Common Terminology Criteria for Adverse Events) grade 4 neutropenia persisted for 7 or more days, CTCAE grade 4 thrombocytopenia or CTCAE grade 3 thrombocytopenia requiring blood transfusion.
2. Non-haematological toxicities: CTCAE grade ≥3 non-haematological toxicities. The following toxicity with neutropenia was defined as DLT.- CTCAE grade 3 febrile neutropenia persisted for over 2 days, Clinically significant laboratory abnormalities of CTCAE grade ≥3 persisted for over 3 days. The following laboratory abnormalities should be defined as DLT. - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): >5.0 × ULN persisted for 7 days or longer - Creatinine: >3.0 × upper limit of normal(ULN) (if the creatinine abnormality was observed even once) - Persistent electrolyte abnormality assessed by the investigator.
Measured: 21 days
Maximum Tolerated Dose (MTD) of Volasertib
Maximum tolerated dose (MTD) of volasertib was the highest dose tested at which DLT was developed in not more than 1 of 6 patients in the course 1.
Measured: 21 days

Secondary outcomes (5)

Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1: Unconfirmed objective response. The patients with complete response (CR) or partial response (PR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: 6 months
Disease Control Rate According to RECIST v1.1
Disease control rate according to RECIST v1.1 - Unconfirmed disease control. The patients with complete response (CR), partial response (PR) or stable disease (SD).
Measured: 6 months
Cmax of Volasertib (BI 6727)
Maximum concentration of an analyte in plasma
Measured: Pharmacokinetic (PK) plasma samples were taken at: 5 minutes predose, 1hour, 2hours (h), 3h, 4h, 8h, 24h, 48h, 72h, 96h, 168h and 336h of course1.
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of Volasertib (BI 6727)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) of Volasertib (BI 6727).
Measured: PK plasma samples were taken at: 5 minutes predose, 1hour, 2hours (h), 3h, 4h, 8h, 24h, 48h, 72h, 96h, 168h and 336h of course1.
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 up to the Last Quantifiable Data Point (AUC0-tz) of Volasertib (BI 6727)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 up to the last quantifiable data point (AUC0-tz) of Volasertib (BI 6727).
Measured: PK plasma samples were taken at: 5 minutes predose, 1hour, 2hours (h), 3h, 4h, 8h, 24h, 48h, 72h, 96h, 168h and 336h of course1.

Timeline

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

25 Apr 201115 May 2014

First posted5 May 2011 (estimated)
Study start25 Apr 2011
Primary completion27 Aug 2012
Study completion15 May 2014

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: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01348347
Sponsor's protocol ID: 1230.15
Status last verified: Aug 2018
First submitted: 29 Apr 2011
Last updated: 6 Aug 2018
Results posted: Yes, on ClinicalTrials.gov

Publications

Nokihara H, Yamada Y, Fujiwara Y, Yamamoto N, Wakui H, Nakamichi S, Kitazono S, Inoue K, Harada A, Taube T, Takeuchi Y, Tamura T. Phase I trial of volasertib, a Polo-like kinase inhibitor, in Japanese patients with advanced solid tumors. Invest New Drugs. 2016 Feb;34(1):66-74. doi: 10.1007/s10637-015-0300-0. Epub 2015 Dec 2.
PubMed 26627079

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 6 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label Phase I Study of Once Every Three Weeks Intravenous Treatment With BI 6727 in Japanese Patients With Advanced Solid Tumours
ClinicalTrials.gov ID: NCT01348347
Acronym / sponsor ID: 1230.15
Conditions: Neoplasms
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 25 Apr 2011 (actual)
Primary completion: 27 Aug 2012 (actual)
Study completion: 15 May 2014 (actual)
First posted: 5 May 2011 (estimated)
Results: Posted 6 Aug 2018

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	Experimental	Drug: Volasertib, low dose, d1q3w, Drug: Volasertib, middle dose, d1q3w, Drug: Volasertib, high dose, d1q3wPatient to receive low, middle and high doses of Volasertib IV

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (17 listed)

Patients with histologically or cytologically confirmed according to the discretion of the investigator
Patients who have advanced, non-resectable and/or metastatic solid tumours according to the discretion of the investigator
Patients who have failed conventional treatment, or for whom no therapy of proved efficacy exists, or who are not amenable to established forms of treatment according to the discretion of the investigator
Age >=20 years old at the time of informed consent
Written informed consent

Key exclusion criteria (19 listed)

Major surgery within 4 weeks prior to registration or the side effects/toxicities of such surgery that have not recovered to CTCAE grade =1
Known seropositivity to human immunodeficiency virus (HIV) antibody, hepatitis B antigen or hepatitis C antibody
Accumulation of coelomic fluid (e.g. pleural effusion, ascites fluid) requiring treatment during the trial (Patients are eligible if treated curatively and with no evidence of recurrence.)
Current symptomatic brain metastases or patients who require treatment of the brain metastases
Previous double cancers. Other tumours (except for non-invasive and/or non-melanomatous skin cancer, completely removed in situ carcinoma of the epithelium or mucosa) treated curatively and with no evidence of recurrence for at least 5 years prior to the initial study treatment will be eligible.

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
Volasertib, low dose, d1q3wPatient to receive low dose of Volasertib IV	Drug	Volasertib
Volasertib, middle dose, d1q3wPatient to receive middle dose of Volasertib IV	Drug	Volasertib
Volasertib, high dose, d1q3wPatient to receive high dose of Volasertib IV	Drug	Volasertib

Primary outcome

Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD).
Time frame: 21 days
The following drug-related adverse events (AE) were defined as DLT; 1. Haematological toxicities: CTCAE(Common Terminology Criteria for Adverse Events) grade 4 neutropenia persisted for 7 or more days, CTCAE grade 4 thrombocytopenia or CTCAE grade 3 thrombocytopenia requiring blood transfusion. 2. Non-haematological toxicities: CTCAE grade ≥3 non-haematological toxicities. The following toxicity with neutropenia was defined as DLT.- CTCAE grade 3 febrile neutropenia persisted for over 2 days, Clinically significant laboratory abnormalities of CTCAE grade ≥3 persisted for over 3 days. The following laboratory abnormalities should be defined as DLT. - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): >5.0 × ULN persisted for 7 days or longer - Creatinine: >3.0 × upper limit of normal(ULN) (if the creatinine abnormality was observed even once) - Persistent electrolyte abnormality assessed by the investigator.
Maximum Tolerated Dose (MTD) of Volasertib
Time frame: 21 days
Maximum tolerated dose (MTD) of volasertib was the highest dose tested at which DLT was developed in not more than 1 of 6 patients in the course 1.

5 secondary outcomes

Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
Time frame: 6 months
Disease Control Rate According to RECIST v1.1
Time frame: 6 months
Cmax of Volasertib (BI 6727)
Time frame: Pharmacokinetic (PK) plasma samples were taken at: 5 minutes predose, 1hour, 2hours (h), 3h, 4h, 8h, 24h, 48h, 72h, 96h, 168h and 336h of course1.
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of Volasertib (BI 6727)
Time frame: PK plasma samples were taken at: 5 minutes predose, 1hour, 2hours (h), 3h, 4h, 8h, 24h, 48h, 72h, 96h, 168h and 336h of course1.
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 up to the Last Quantifiable Data Point (AUC0-tz) of Volasertib (BI 6727)
Time frame: PK plasma samples were taken at: 5 minutes predose, 1hour, 2hours (h), 3h, 4h, 8h, 24h, 48h, 72h, 96h, 168h and 336h of course1.

Results and safety

Results posted to the registry on 6 Aug 2018, 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 200 mg Cohort	3	0
Volasertib 300 mg Cohort	6	0
Volasertib 350 mg Cohort	6	0

Primary outcome: Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD).

Time frame: 21 days. Number. Unit: Participants

Measure	Volasertib 200 mg Cohort n = 3	Volasertib 300 mg Cohort n = 6	Volasertib 350 mg Cohort n = 6
Value	0	0	2

Population analysed: The treated set(TS) - All patients who received ≥1 dose of study medication (volasertib) were included in the treated set.

Primary outcome: Maximum Tolerated Dose (MTD) of Volasertib

Time frame: 21 days. Number. Unit: mg

Measure	Volasertib Cohort n = 15
Value	300

Population analysed: The treated set(TS) - All patients who received ≥1 dose of study medication (volasertib) were included in the treated set.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the day of informed consent(-14 days) until the follow-up visit, 72 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Volasertib 200 mg Cohort	0 of 3 (0%)	3 of 3 (100%)	Not reported
Volasertib 300 mg Cohort	0 of 6 (0%)	6 of 6 (100%)	Not reported
Volasertib 350 mg Cohort	1 of 6 (16.7%)	6 of 6 (100%)	Not reported

Limitations and caveats (from the sponsor): 250 mg dose of Volasertib was planned, as needed. However the 250 mg intermediate cohort had not been implemented in this trial.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26627079Nokihara H, Yamada Y, Fujiwara Y, Yamamoto N, Wakui H, Nakamichi S, Kitazono S, Inoue K, Harada A, Taube T, Takeuchi Y, Tamura T. Phase I trial of volasertib, a Polo-like kinase inhibitor, in Japanese patients with advanced solid tumors. Invest New Drugs. 2016 Feb;34(1):66-74. doi: 10.1007/s10637-015-0300-0. Epub 2015 Dec 2.
Related InfoLink provided by the sponsor.

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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

1 site 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, low dose, d1q3w, Volasertib, middle dose, d1q3w and Volasertib, high dose, d1q3w in people with Neoplasms, run by Boehringer Ingelheim at 1 site in Japan.

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 17 inclusion and 19 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 6 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. 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 6 Aug 2018). 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?

Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD). (time frame: 21 days). 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 NCT01348347, 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 6 Aug 2018.