Intravenous BI 6727 (Volasertib) in 2nd Line Treatment of Urothelial Cancer

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BI 6727, IV infusion

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan
    • 1230.2.51 Boehringer Ingelheim Investigational Site
  • Taipei, Taiwan
    • 1230.2.50 Boehringer Ingelheim Investigational Site
• United States
  • California
    • Beverly Hills, California, United States
      • 1230.2.5 Boehringer Ingelheim Investigational Site
    • Los Angeles, California, United States
      • 1230.2.10 Boehringer Ingelheim Investigational Site
  • Florida
    • Miami, Florida, United States
      • 1230.2.34 Boehringer Ingelheim Investigational Site
    • Orlando, Florida, United States
      • 1230.2.29 Boehringer Ingelheim Investigational Site
  • Illinois
    • Chicago, Illinois, United States
      • 1230.2.6 Boehringer Ingelheim Investigational Site
    • Joliet, Illinois, United States
      • 1230.2.17 Boehringer Ingelheim Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States
      • 1230.2.24 Boehringer Ingelheim Investigational Site
  • Maryland
    • Baltimore, Maryland, United States
      • 1230.2.1 Boehringer Ingelheim Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States
      • 1230.2.25 Boehringer Ingelheim Investigational Site
    • Las Vegas, Nevada, United States
      • 1230.2.36 Boehringer Ingelheim Investigational Site
  • New Hampshire
    • Lebanon, New Hampshire, United States
      • 1230.2.19 Boehringer Ingelheim Investigational Site
  • New York
    • New York, New York, United States
      • 1230.2.20 Boehringer Ingelheim Investigational Site
    • New York, New York, United States
      • 1230.2.23 Boehringer Ingelheim Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States
      • 1230.2.12 Boehringer Ingelheim Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • 1230.2.4 Boehringer Ingelheim Investigational Site
  • Texas
    • Beaumont, Texas, United States
      • 1230.2.38 Boehringer Ingelheim Investigational Site
    • Tyler, Texas, United States
      • 1230.2.41 Boehringer Ingelheim Investigational Site
    • Webster, Texas, United States
      • 1230.2.43 Boehringer Ingelheim Investigational Site
  • Virginia
    • Fairfax, Virginia, United States
      • 1230.2.44 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Histologically or cytologically confirmed urothelial cancer of the bladder, ureters or renal pelvis.
2. 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.
3. Male or female patient aged 18 years or older
4. Life expectancy of at least three (3) months
5. Eastern Co-operative Oncology Group performance score of 2 or less
6. 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
7. 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

Exclusion criteria:

1. More than one prior regimen of chemotherapy including prior adjuvant therapy
2. Brain metastases
3. Patients with bone metastasis as the only site of disease are excluded
4. 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.
5. QTc prolongation deemed clinically relevant by the investigator
6. Second malignancy currently requiring active therapy
7. Other active malignancy diagnosed within the past 3 years (other than non melanomatous skin cancer and cervical intraepithelial neoplasia)
8. Absolute neutrophil count (ANC) <1,500/µl
9. Platelet count <100,000/µl
10. Hemoglobin <9 g/dl
11. Total bilirubin >1.5 mg/dl
12. 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
13. Serum creatinine >1.5 x ULN
14. Chemo-, Radio- or immunotherapy within the past 4 weeks. This does not apply to steroids and bisphosphonates.
15. Active infectious disease, or HIV, Hepatitis-B or -C infection
16. Active drug or alcohol abuse
17. 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
18. Pregnancy or breast feeding
19. 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.
20. Prior treatment with Polo-like kinase 1 (Plk1) inhibitor
21. Patient unable to comply with the protocol
22. Any known hypersensitivity to the trial drugs or their excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: single arm; open label	Drug: BI 6727, IV infusion; phase II

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From first drug administration until end of study, up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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).	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.	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	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	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	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	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	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	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).	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.	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	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	Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Platelets	Difference from baseline in laboratory parameter Platelets	Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Neutrophils	Difference from baseline in laboratory parameter Neutrophils	Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Lymphocytes	Difference from baseline in laboratory parameter Lymphocytes	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	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	Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Alkaline Phosphatase	Difference from baseline in laboratory parameter Alkaline phosphatase	Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Creatinine	Difference from baseline in laboratory parameter Creatinine	Baseline and last value on treatment (up to 2 years)
Laboratory Investigation: Total Bilirubin	Difference from baseline in laboratory parameter total Bilirubin	Baseline and last value on treatment (up to 2 years)

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2009
• Primary Completion (Actual): September 19, 2011
• Study Completion (Actual): September 19, 2011

Study Registration Dates

• First Submitted: November 24, 2009
• First Submitted That Met QC Criteria: December 1, 2009
• First Posted (Estimate): December 2, 2009

Study Record Updates

• Last Update Posted (Actual): November 22, 2017
• Last Update Submitted That Met QC Criteria: October 23, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: 1230.2