NeoplasmsPhase 2NCT01023958
Intravenous BI 6727 (Volasertib) in 2nd Line Treatment of Urothelial Cancer
A Phase 2 study testing BI 6727, IV infusion in people with Neoplasms, run by Boehringer Ingelheim at 21 sites in 2 countries.
Trial summary
The primary objective of this trial is to evaluate the efficacy and safety of BI 6727 in patients with locally advanced, metastatic or recurrent urothelial cancer after failure of first line or adjuvant/neoadjuvant chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- BI 6727, IV infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 21 sitesin 2 countries
- Study dates
- 19 Nov 2009to 19 Sep 2011
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed urothelial cancer of the bladder, ureters or renal pelvis.
- Patients with stage III, IV or recurrent urothelial cancer of the bladder, ureter or renal pelvis after failure or recurrence after first line or adjuvant/neoadjuvant chemotherapy. Recurrence is defined as relapse within 2 years after cessation of prior first-line chemotherapy.
- Male or female patient aged 18 years or older
- Life expectancy of at least three (3) months
- Eastern Co-operative Oncology Group performance score of 2 or less
- At least one target tumor lesion that has not been irradiated within the past three months and that can accurately be measured by magnetic resonance imaging (MRI) or computed tomography (CT) in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT
- The patient must have given written informed consent prior to inclusion into the trial which must be consistent with the International Conference on Harmonization, Good Clinical Practice (ICH-GCP) and local legislation
Who cannot join
- More than one prior regimen of chemotherapy including prior adjuvant therapy
- Brain metastases
- Patients with bone metastasis as the only site of disease are excluded
- Serious illness or organ system dysfunction, which in the opinion of the investigator, would either compromise patient safety, interfere with the evaluation of the safety of the test drug or limit compliance with trial requirements.
- QTc prolongation deemed clinically relevant by the investigator
- Second malignancy currently requiring active therapy
Show all 22Show fewer
- Other active malignancy diagnosed within the past 3 years (other than non melanomatous skin cancer and cervical intraepithelial neoplasia)
- Absolute neutrophil count (ANC) <1,500/µl
- Platelet count <100,000/µl
- Hemoglobin <9 g/dl
- Total bilirubin >1.5 mg/dl
- Aspartate amino transferase (AST) and/or alanine amino transferase (ALT) >2.5 x ULN, or aspartate amino transferase (AST) and/or alanine amino transferase (ALT) >5 x ULN in case of known liver metastases
- Serum creatinine >1.5 x ULN
- Chemo-, Radio- or immunotherapy within the past 4 weeks. This does not apply to steroids and bisphosphonates.
- Active infectious disease, or HIV, Hepatitis-B or -C infection
- Active drug or alcohol abuse
- Women and men who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial
- Pregnancy or breast feeding
- Treatment with any investigational drug within the past 4 weeks or within less than four half-life times of the investigational drug before treatment with the trial drug and/or persistence of toxicities of prior anticancer therapies which are deemed to be clinically relevant.
- Prior treatment with Polo-like kinase 1 (Plk1) inhibitor
- Patient unable to comply with the protocol
- Any known hypersensitivity to the trial drugs or their excipients
Trial locations and contacts
21 sites in 2 countries.
21 sites in 2 countries
United States19 sites
1230.2.1 Boehringer Ingelheim Investigational Site
Baltimore, Maryland
1230.2.38 Boehringer Ingelheim Investigational Site
Beaumont, Texas
1230.2.5 Boehringer Ingelheim Investigational Site
Beverly Hills, California
1230.2.12 Boehringer Ingelheim Investigational Site
Charlotte, North Carolina
1230.2.6 Boehringer Ingelheim Investigational Site
Chicago, Illinois
1230.2.44 Boehringer Ingelheim Investigational Site
Fairfax, Virginia
1230.2.17 Boehringer Ingelheim Investigational Site
Joliet, Illinois
1230.2.25 Boehringer Ingelheim Investigational Site
Las Vegas, Nevada
1230.2.36 Boehringer Ingelheim Investigational Site
Las Vegas, Nevada
1230.2.19 Boehringer Ingelheim Investigational Site
Lebanon, New Hampshire
1230.2.10 Boehringer Ingelheim Investigational Site
Los Angeles, California
1230.2.24 Boehringer Ingelheim Investigational Site
Metairie, Louisiana
1230.2.34 Boehringer Ingelheim Investigational Site
Miami, Florida
1230.2.20 Boehringer Ingelheim Investigational Site
New York, New York
1230.2.23 Boehringer Ingelheim Investigational Site
New York, New York
1230.2.29 Boehringer Ingelheim Investigational Site
Orlando, Florida
1230.2.4 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania
1230.2.41 Boehringer Ingelheim Investigational Site
Tyler, Texas
1230.2.43 Boehringer Ingelheim Investigational Site
Webster, Texas
Taiwan2 sites
1230.2.51 Boehringer Ingelheim Investigational Site
Tainan
1230.2.50 Boehringer Ingelheim Investigational Site
Taipei
About this study
Official title: An Open-label, Single-arm, Phase II Trial of Intravenous BI 6727 in Patients With Locally Advanced, Metastatic or Recurrent Urothelial Cancer of the Bladder, Renal Pelvis, or Ureters After Failure of Prior Chemotherapy
The primary objective of this trial is to evaluate the efficacy and safety of BI 6727 in patients with locally advanced, metastatic or recurrent urothelial cancer after failure of first line or adjuvant/neoadjuvant chemotherapy.
- Conditions
- Neoplasms
- Being tested
- BI 6727, IV infusion
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 6727, IV infusionDrug
phase II
| Study group | Role | What they receive |
|---|---|---|
| single arm | Experimental | open label Receives: Drug: BI 6727, IV infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Tumour Response According to RECIST Criteria
Objective tumor response, defined as complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Measured: From first drug administration until end of study, up to 2 years
Secondary outcomes (23)
Progression-free Survival
Progression-free survival (PFS) is the time from first treatment to the occurrence of tumor progression or death, whichever occurs first. Disease progression is defined according to the RECIST guideline but also includes the investigators' assessment which may, in some cases, include only clinical progression (deterioration of general health status per investigator). PFS was analyzed with the Kaplan-Meier curve. Greenwood's variance estimate was used to form confidence intervals.
Patients without evidence of disease progression were to be censored at the last image date.
Measured: Time from first treatment to the occurrence of tumor progression or death, up to 2 years
Overall Survival
Overall survival (OS) is the time from first infusion to death. Patients who were alive at the time of analysis or lost to follow-up were censored at the last follow-up date when they were known to be alive.
Overall survival was analyzed with the Kaplan-Meier curve. Greenwood's variance estimate was used to form confidence intervals.
Measured: Time from first infusion to death, up to 2 years
Duration of Overall Response
The duration of overall response is measured from the time of first response (CR or PR) to progression or death whichever occurs first.
Measured: From the time of first response (CR or PR) to progression or death, up to 2 years
Disease Control Rate
Disease control rate. Disease control is defined as having a best overall response of complete response (CR), partial response (PR) or stable disease (SD).
Measured: From first drug administration until end of study, up to 2 years
Duration of Disease Control
Disease control is defined as having a best overall response of CR, PR, or SD. The duration of disease control is measured from the time of first response to progression or death whichever occurs first.
Measured: Time of first response to progression or death, up to 2 years
AUC0-∞ of Volasertib
Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) of volasertib
Measured: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
Cmax of Volasertib
Maximum measured concentration in plasma (Cmax) of volasertib
Measured: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
t1/2 of Volasertib
Terminal half-life (t1/2) of volasertib
Measured: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
CL of Volasertib
Total plasma clearance after intravascular administration (CL) of volasertib
Measured: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
Vss of Volasertib
Apparent volume of distribution at steady state following intravascular administration (Vss) of volasertib
Measured: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
Tmax of Volasertib
Time from dosing to maximum measured concentration (Tmax) of volasertib
Measured: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
Occurrence and Intensity of AE's Graded According to CTCAE
Occurrence and intensity of adverse events (AEs) graded according to Common Toxicity Criteria of Adverse Events (CTCAE).
The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Measured: From first drug administration until end of study, up to 2 years
Occurrence of Unacceptable Toxicity
Occurrence of unacceptable toxicity is defined by CTCAE as as drug related CTCAE Grade 3 or greater non-hematological toxicity (except emesis or diarrhea responding to supportive treatment); drug-related CTCAE Grade 4 neutropenia for seven or more days and / or complicated by infection; or drug-related CTCAE Grade 4 thrombocytopenia.
Measured: From first drug administration up to 21 days after final administration, up to 2 years
Laboratory Investigation: Haemoglobin
Difference from baseline in laboratory parameter Haemoglobin
Measured: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: White Blood Cell Count
Difference from baseline in laboratory parameter white blood cell count
Measured: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Platelets
Difference from baseline in laboratory parameter Platelets
Measured: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Neutrophils
Difference from baseline in laboratory parameter Neutrophils
Measured: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Lymphocytes
Difference from baseline in laboratory parameter Lymphocytes
Measured: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: AST/GOT, SGOT
Difference from baseline in laboratory parameter Aspartate aminotransferase(AST)/GOT, SGOT
Measured: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: ALT/GPT, SGPT
Difference from baseline in laboratory parameter Alanine aminotransferase(ALT)/GPT, SGPT
Measured: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Alkaline Phosphatase
Difference from baseline in laboratory parameter Alkaline phosphatase
Measured: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Creatinine
Difference from baseline in laboratory parameter Creatinine
Measured: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Total Bilirubin
Difference from baseline in laboratory parameter total Bilirubin
Measured: Baseline and last value on treatment (up to 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2009 (estimated)
- Study start19 Nov 2009
- Primary completion19 Sep 2011
- Study completion19 Sep 2011
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01023958
- Sponsor's protocol ID
- 1230.2
- Status last verified
- Oct 2017
- First submitted
- 24 Nov 2009
- Last updated
- 22 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Stadler WM, Vaughn DJ, Sonpavde G, Vogelzang NJ, Tagawa ST, Petrylak DP, Rosen P, Lin CC, Mahoney J, Modi S, Lee P, Ernstoff MS, Su WC, Spira A, Pilz K, Vinisko R, Schloss C, Fritsch H, Zhao C, Carducci MA. An open-label, single-arm, phase 2 trial of the Polo-like kinase inhibitor volasertib (BI 6727) in patients with locally advanced or metastatic urothelial cancer. Cancer. 2014 Apr 1;120(7):976-82. doi: 10.1002/cncr.28519. Epub 2013 Dec 11.
PubMed 24339028
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-arm, Phase II Trial of Intravenous BI 6727 in Patients With Locally Advanced, Metastatic or Recurrent Urothelial Cancer of the Bladder, Renal Pelvis, or Ureters After Failure of Prior Chemotherapy
- ClinicalTrials.gov ID
- NCT01023958
- Acronym / sponsor ID
- 1230.2
- Conditions
- Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 19 Nov 2009 (actual)
- Primary completion
- 19 Sep 2011 (actual)
- Study completion
- 19 Sep 2011 (actual)
- First posted
- 2 Dec 2009 (estimated)
- Results
- Posted 22 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this trial is to evaluate the efficacy and safety of BI 6727 in patients with locally advanced, metastatic or recurrent urothelial cancer after failure of first line or adjuvant/neoadjuvant chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single arm | Experimental | Drug: BI 6727, IV infusionopen label |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histologically or cytologically confirmed urothelial cancer of the bladder, ureters or renal pelvis.
- Patients with stage III, IV or recurrent urothelial cancer of the bladder, ureter or renal pelvis after failure or recurrence after first line or adjuvant/neoadjuvant chemotherapy. Recurrence is defined as relapse within 2 years after cessation of prior first-line chemotherapy.
- Male or female patient aged 18 years or older
- Life expectancy of at least three (3) months
- Eastern Co-operative Oncology Group performance score of 2 or less
Key exclusion criteria (22 listed)
- More than one prior regimen of chemotherapy including prior adjuvant therapy
- Brain metastases
- Patients with bone metastasis as the only site of disease are excluded
- Serious illness or organ system dysfunction, which in the opinion of the investigator, would either compromise patient safety, interfere with the evaluation of the safety of the test drug or limit compliance with trial requirements.
- QTc prolongation deemed clinically relevant by the investigator
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 |
|---|---|---|
| BI 6727, IV infusionphase II | Drug | single arm |
Primary outcome
Objective Tumour Response According to RECIST Criteria
Time frame: From first drug administration until end of study, up to 2 years
Objective tumor response, defined as complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
23 secondary outcomes
Progression-free Survival
Time frame: Time from first treatment to the occurrence of tumor progression or death, up to 2 years
Overall Survival
Time frame: Time from first infusion to death, up to 2 years
Duration of Overall Response
Time frame: From the time of first response (CR or PR) to progression or death, up to 2 years
Disease Control Rate
Time frame: From first drug administration until end of study, up to 2 years
Duration of Disease Control
Time frame: Time of first response to progression or death, up to 2 years
AUC0-∞ of Volasertib
Time frame: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
Cmax of Volasertib
Time frame: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
t1/2 of Volasertib
Time frame: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
CL of Volasertib
Time frame: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
Vss of Volasertib
Time frame: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
Tmax of Volasertib
Time frame: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
Occurrence and Intensity of AE's Graded According to CTCAE
Time frame: From first drug administration until end of study, up to 2 years
Occurrence of Unacceptable Toxicity
Time frame: From first drug administration up to 21 days after final administration, up to 2 years
Laboratory Investigation: Haemoglobin
Time frame: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: White Blood Cell Count
Time frame: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Platelets
Time frame: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Neutrophils
Time frame: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Lymphocytes
Time frame: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: AST/GOT, SGOT
Time frame: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: ALT/GPT, SGPT
Time frame: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Alkaline Phosphatase
Time frame: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Creatinine
Time frame: Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Total Bilirubin
Time frame: Baseline and last value on treatment (up to 2 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24339028Stadler WM, Vaughn DJ, Sonpavde G, Vogelzang NJ, Tagawa ST, Petrylak DP, Rosen P, Lin CC, Mahoney J, Modi S, Lee P, Ernstoff MS, Su WC, Spira A, Pilz K, Vinisko R, Schloss C, Fritsch H, Zhao C, Carducci MA. An open-label, single-arm, phase 2 trial of the Polo-like kinase inhibitor volasertib (BI 6727) in patients with locally advanced or metastatic urothelial cancer. Cancer. 2014 Apr 1;120(7):976-82. doi: 10.1002/cncr.28519. Epub 2013 Dec 11.
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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
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BI 6727, IV infusion in people with Neoplasms, run by Boehringer Ingelheim at 21 sites in 2 countries.
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 7 inclusion and 22 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 22 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Taiwan. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 22 Nov 2017). 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?
Objective Tumour Response According to RECIST Criteria (time frame: From first drug administration until end of study, up to 2 years). 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 NCT01023958, 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 22 Nov 2017.