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

Boehringer Ingelheim50 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neoplasms

Interventions

BI 6727, IV infusionDRUG

phase II

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (21)

1230.2.5 Boehringer Ingelheim Investigational Site

Beverly Hills, California, United States

Outcomes

Primary Outcomes

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.

Time frame: From first drug administration until end of study, up to 2 years

Secondary Outcomes

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 frame: 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 frame: 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.

Time frame: 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).

Data from ClinicalTrials.gov

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1230.2.10 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

1230.2.34 Boehringer Ingelheim Investigational Site

Miami, Florida, United States

1230.2.29 Boehringer Ingelheim Investigational Site

Orlando, Florida, United States

1230.2.6 Boehringer Ingelheim Investigational Site

Chicago, Illinois, United States

1230.2.17 Boehringer Ingelheim Investigational Site

Joliet, Illinois, United States

1230.2.24 Boehringer Ingelheim Investigational Site

Metairie, Louisiana, United States

1230.2.1 Boehringer Ingelheim Investigational Site

Baltimore, Maryland, United States

1230.2.25 Boehringer Ingelheim Investigational Site

Las Vegas, Nevada, United States

1230.2.36 Boehringer Ingelheim Investigational Site

Las Vegas, Nevada, United States

...and 11 more locations

Time frame: 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 frame: 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

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

Maximum measured concentration in plasma (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

Terminal half-life (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

Total plasma clearance after intravascular administration (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

Apparent volume of distribution at steady state following intravascular administration (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 from dosing to maximum measured concentration (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

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).

Time frame: 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.

Time frame: 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