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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01023958
Recruitment Status : Completed
First Posted : December 2, 2009
Results First Posted : November 22, 2017
Last Update Posted : November 22, 2017
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

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.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: BI 6727, IV infusion Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 19, 2009
Actual Primary Completion Date : September 19, 2011
Actual Study Completion Date : September 19, 2011

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: single arm
open label
Drug: BI 6727, IV infusion
phase II




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Progression-free Survival [ Time Frame: Time from first treatment to the occurrence of tumor progression or death, up to 2 years ]

    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.


  2. Overall Survival [ Time Frame: Time from first infusion to death, up to 2 years ]

    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.


  3. Duration of Overall Response [ Time Frame: From the time of first response (CR or PR) to progression or death, up to 2 years ]
    The duration of overall response is measured from the time of first response (CR or PR) to progression or death whichever occurs first.

  4. Disease Control Rate [ Time Frame: From first drug administration until end of study, up to 2 years ]
    Disease control rate. Disease control is defined as having a best overall response of complete response (CR), partial response (PR) or stable disease (SD).

  5. Duration of Disease Control [ Time Frame: Time of first response to progression or death, up to 2 years ]
    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.

  6. 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 ]
    Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) of volasertib

  7. 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 ]
    Maximum measured concentration in plasma (Cmax) of volasertib

  8. 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 ]
    Terminal half-life (t1/2) of volasertib

  9. 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 ]
    Total plasma clearance after intravascular administration (CL) of volasertib

  10. 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 ]
    Apparent volume of distribution at steady state following intravascular administration (Vss) of volasertib

  11. 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 ]
    Time from dosing to maximum measured concentration (Tmax) of volasertib

  12. 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 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).


  13. Occurrence of Unacceptable Toxicity [ Time Frame: From first drug administration up to 21 days after final administration, up to 2 years ]
    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.

  14. Laboratory Investigation: Haemoglobin [ Time Frame: Baseline and last value on treatment (up to 2 years) ]
    Difference from baseline in laboratory parameter Haemoglobin

  15. Laboratory Investigation: White Blood Cell Count [ Time Frame: Baseline and last value on treatment (up to 2 years) ]
    Difference from baseline in laboratory parameter white blood cell count

  16. Laboratory Investigation: Platelets [ Time Frame: Baseline and last value on treatment (up to 2 years) ]
    Difference from baseline in laboratory parameter Platelets

  17. Laboratory Investigation: Neutrophils [ Time Frame: Baseline and last value on treatment (up to 2 years) ]
    Difference from baseline in laboratory parameter Neutrophils

  18. Laboratory Investigation: Lymphocytes [ Time Frame: Baseline and last value on treatment (up to 2 years) ]
    Difference from baseline in laboratory parameter Lymphocytes

  19. Laboratory Investigation: AST/GOT, SGOT [ Time Frame: Baseline and last value on treatment (up to 2 years) ]
    Difference from baseline in laboratory parameter Aspartate aminotransferase(AST)/GOT, SGOT

  20. Laboratory Investigation: ALT/GPT, SGPT [ Time Frame: Baseline and last value on treatment (up to 2 years) ]
    Difference from baseline in laboratory parameter Alanine aminotransferase(ALT)/GPT, SGPT

  21. Laboratory Investigation: Alkaline Phosphatase [ Time Frame: Baseline and last value on treatment (up to 2 years) ]
    Difference from baseline in laboratory parameter Alkaline phosphatase

  22. Laboratory Investigation: Creatinine [ Time Frame: Baseline and last value on treatment (up to 2 years) ]
    Difference from baseline in laboratory parameter Creatinine

  23. Laboratory Investigation: Total Bilirubin [ Time Frame: Baseline and last value on treatment (up to 2 years) ]
    Difference from baseline in laboratory parameter total Bilirubin



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01023958


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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01023958     History of Changes
Other Study ID Numbers: 1230.2
First Posted: December 2, 2009    Key Record Dates
Results First Posted: November 22, 2017
Last Update Posted: November 22, 2017
Last Verified: October 2017