Clinical trial NCT01023958: Intravenous BI 6727 (Volasertib) in 2nd Line Treatment of Urothelial Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-12-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective Tumour Response According to RECIST Criteria
timeFrame: From first drug administration until end of study, up to 2 years
Secondary outcomes:
measure: Progression-free Survival
timeFrame: Time from first treatment to the occurrence of tumor progression or death, up to 2 years
measure: Overall Survival
timeFrame: Time from first infusion to death, up to 2 years
measure: Duration of Overall Response
timeFrame: From the time of first response (CR or PR) to progression or death, up to 2 years
measure: Disease Control Rate
timeFrame: From first drug administration until end of study, up to 2 years
measure: Duration of Disease Control
timeFrame: Time of first response to progression or death, up to 2 years
measure: AUC0-∞ of Volasertib
timeFrame: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
measure: Cmax of Volasertib
timeFrame: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
measure: t1/2 of Volasertib
timeFrame: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
measure: CL of Volasertib
timeFrame: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
measure: Vss of Volasertib
timeFrame: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
measure: Tmax of Volasertib
timeFrame: 5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion
measure: Occurrence and Intensity of AE's Graded According to CTCAE
timeFrame: From first drug administration until end of study, up to 2 years
measure: Occurrence of Unacceptable Toxicity
timeFrame: From first drug administration up to 21 days after final administration, up to 2 years
measure: Laboratory Investigation: Haemoglobin
timeFrame: Baseline and last value on treatment (up to 2 years)
measure: Laboratory Investigation: White Blood Cell Count
timeFrame: Baseline and last value on treatment (up to 2 years)
measure: Laboratory Investigation: Platelets
timeFrame: Baseline and last value on treatment (up to 2 years)
measure: Laboratory Investigation: Neutrophils
timeFrame: Baseline and last value on treatment (up to 2 years)
measure: Laboratory Investigation: Lymphocytes
timeFrame: Baseline and last value on treatment (up to 2 years)
measure: Laboratory Investigation: AST/GOT, SGOT
timeFrame: Baseline and last value on treatment (up to 2 years)
measure: Laboratory Investigation: ALT/GPT, SGPT
timeFrame: Baseline and last value on treatment (up to 2 years)
measure: Laboratory Investigation: Alkaline Phosphatase
timeFrame: Baseline and last value on treatment (up to 2 years)
measure: Laboratory Investigation: Creatinine
timeFrame: Baseline and last value on treatment (up to 2 years)
measure: Laboratory Investigation: Total Bilirubin
timeFrame: Baseline and last value on treatment (up to 2 years)
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: 1230.2.5 Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: 1230.2.10 Boehringer Ingelheim Investigational Site
state: California
city: Miami
country: United States
facility: 1230.2.34 Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: 1230.2.29 Boehringer Ingelheim Investigational Site
state: Florida
city: Chicago
country: United States
facility: 1230.2.6 Boehringer Ingelheim Investigational Site
state: Illinois
city: Joliet
country: United States
facility: 1230.2.17 Boehringer Ingelheim Investigational Site
state: Illinois
city: Metairie
country: United States
facility: 1230.2.24 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: 1230.2.1 Boehringer Ingelheim Investigational Site
state: Maryland
city: Las Vegas
country: United States
facility: 1230.2.25 Boehringer Ingelheim Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: 1230.2.36 Boehringer Ingelheim Investigational Site
state: Nevada
city: Lebanon
country: United States
facility: 1230.2.19 Boehringer Ingelheim Investigational Site
state: New Hampshire
city: New York
country: United States
facility: 1230.2.20 Boehringer Ingelheim Investigational Site
state: New York
city: New York
country: United States
facility: 1230.2.23 Boehringer Ingelheim Investigational Site
state: New York
city: Charlotte
country: United States
facility: 1230.2.12 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: 1230.2.4 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Beaumont
country: United States
facility: 1230.2.38 Boehringer Ingelheim Investigational Site
state: Texas
city: Tyler
country: United States
facility: 1230.2.41 Boehringer Ingelheim Investigational Site
state: Texas
city: Webster
country: United States
facility: 1230.2.43 Boehringer Ingelheim Investigational Site
state: Texas
city: Fairfax
country: United States
facility: 1230.2.44 Boehringer Ingelheim Investigational Site
state: Virginia
city: Tainan
country: Taiwan
facility: 1230.2.51 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1230.2.50 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.