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BI 6727 (Volasertib) Monotherapy Phase I Trial in Japanese Patients With Advanced Solid Tumours

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: NCT01348347
Recruitment Status : Completed
First Posted : May 5, 2011
Results First Posted : August 6, 2018
Last Update Posted : August 6, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
This open-label phase I dose escalation trial, 1230.15, is the first trial with Volasertib in Japanese advanced cancer patients. The trial will investigate the maximum tolerated dose (MTD), safety, tolerability, and preliminary efficacy of this specific polo-like kinase 1 (Plk1) inhibitor in advanced cancer patients.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Volasertib, low dose, d1q3w Drug: Volasertib, middle dose, d1q3w Drug: Volasertib, high dose, d1q3w Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Phase I Study of Once Every Three Weeks Intravenous Treatment With BI 6727 in Japanese Patients With Advanced Solid Tumours
Actual Study Start Date : April 25, 2011
Actual Primary Completion Date : August 27, 2012
Actual Study Completion Date : May 15, 2014

Arm Intervention/treatment
Experimental: Volasertib
Patient to receive low, middle and high doses of Volasertib IV
Drug: Volasertib, low dose, d1q3w
Patient to receive low dose of Volasertib IV

Drug: Volasertib, middle dose, d1q3w
Patient to receive middle dose of Volasertib IV

Drug: Volasertib, high dose, d1q3w
Patient to receive high dose of Volasertib IV




Primary Outcome Measures :
  1. Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD). [ Time Frame: 21 days ]

    The following drug-related adverse events (AE) were defined as DLT;

    1. Haematological toxicities: CTCAE(Common Terminology Criteria for Adverse Events) grade 4 neutropenia persisted for 7 or more days, CTCAE grade 4 thrombocytopenia or CTCAE grade 3 thrombocytopenia requiring blood transfusion.
    2. Non-haematological toxicities: CTCAE grade ≥3 non-haematological toxicities. The following toxicity with neutropenia was defined as DLT.- CTCAE grade 3 febrile neutropenia persisted for over 2 days, Clinically significant laboratory abnormalities of CTCAE grade ≥3 persisted for over 3 days. The following laboratory abnormalities should be defined as DLT. - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): >5.0 × ULN persisted for 7 days or longer - Creatinine: >3.0 × upper limit of normal(ULN) (if the creatinine abnormality was observed even once) - Persistent electrolyte abnormality assessed by the investigator.

  2. Maximum Tolerated Dose (MTD) of Volasertib [ Time Frame: 21 days ]
    Maximum tolerated dose (MTD) of volasertib was the highest dose tested at which DLT was developed in not more than 1 of 6 patients in the course 1.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 [ Time Frame: 6 months ]
    Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1: Unconfirmed objective response. The patients with complete response (CR) or partial response (PR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  2. Disease Control Rate According to RECIST v1.1 [ Time Frame: 6 months ]
    Disease control rate according to RECIST v1.1 - Unconfirmed disease control. The patients with complete response (CR), partial response (PR) or stable disease (SD).

  3. Cmax of Volasertib (BI 6727) [ Time Frame: Pharmacokinetic (PK) plasma samples were taken at: 5 minutes predose, 1hour, 2hours (h), 3h, 4h, 8h, 24h, 48h, 72h, 96h, 168h and 336h of course1. ]
    Maximum concentration of an analyte in plasma

  4. Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of Volasertib (BI 6727) [ Time Frame: PK plasma samples were taken at: 5 minutes predose, 1hour, 2hours (h), 3h, 4h, 8h, 24h, 48h, 72h, 96h, 168h and 336h of course1. ]
    Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) of Volasertib (BI 6727).

  5. Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 up to the Last Quantifiable Data Point (AUC0-tz) of Volasertib (BI 6727) [ Time Frame: PK plasma samples were taken at: 5 minutes predose, 1hour, 2hours (h), 3h, 4h, 8h, 24h, 48h, 72h, 96h, 168h and 336h of course1. ]
    Area under the concentration-time curve of the analyte in plasma over the time interval from 0 up to the last quantifiable data point (AUC0-tz) of Volasertib (BI 6727).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Patients with histologically or cytologically confirmed according to the discretion of the investigator
  2. Patients who have advanced, non-resectable and/or metastatic solid tumours according to the discretion of the investigator
  3. Patients who have failed conventional treatment, or for whom no therapy of proved efficacy exists, or who are not amenable to established forms of treatment according to the discretion of the investigator
  4. Age >=20 years old at the time of informed consent
  5. Written informed consent
  6. Life expectancy of at least 12 weeks according to the discretion of the investigator
  7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  8. Recovery to Common Terminology Criteria for Adverse Events (CTCAE) grade =1 of therapy-related toxicities from previous chemo-, hormonal-, immuno-, or radiotherapy (except alopecia and hyperpigmentation)
  9. Adequate bone marrow, renal and hepatic function;

    • Neutrophil count: more than 1500/mm3
    • Platelet count: more than 100 000/mm3
    • Haemoglobin: more than 9.0 g/dL
    • Total bilirubin: less than 1.5 times the upper limit of normal (ULN)
    • Aspartate amino transferase (AST): less than 2.5 × ULN
    • Alanine amino transferase (ALT): less than 2.5 × ULN
    • Serum creatinine: less than 1.5 × ULN
  10. Patients who can be hospitalised during the first course

Exclusion criteria:

  1. Major surgery within 4 weeks prior to registration or the side effects/toxicities of such surgery that have not recovered to CTCAE grade =1
  2. Known seropositivity to human immunodeficiency virus (HIV) antibody, hepatitis B antigen or hepatitis C antibody
  3. Accumulation of coelomic fluid (e.g. pleural effusion, ascites fluid) requiring treatment during the trial (Patients are eligible if treated curatively and with no evidence of recurrence.)
  4. Current symptomatic brain metastases or patients who require treatment of the brain metastases
  5. Previous double cancers. Other tumours (except for non-invasive and/or non-melanomatous skin cancer, completely removed in situ carcinoma of the epithelium or mucosa) treated curatively and with no evidence of recurrence for at least 5 years prior to the initial study treatment will be eligible.
  6. Known history of cardiac dysfunction;

    • Correction of QT intervals according to Fridericias formula (QTc) over 470 ms
    • History of unstable angina pectoris within 6 months or current unstable angina pectoris
    • History of myocardial infarction within 6 months
    • Arrhythmia currently required active therapy
    • Previous and current cardiac failure
    • History of other clinically significant cardiac diseases according to the discretion of the investigator
  7. Pregnant or breastfeeding women
  8. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. implants, injectables, combined oral contraceptives, some intrauterine devices, vasectomised partner, or condoms) during the trial and for at least 6 months after the end of active therapy. Women who are sexually active are premenopausal female patients. Premenopausal female patient is defined as the patient who observed menses within 12 months except for an alternative medical cause. Women who underwent an operation for sterilisation is excluded for this criteria.
  9. Treatment with other investigational drugs within the past 4 weeks before registration or concomitantly with this trial (except for present trial drug)
  10. Chemo-, radio-, immuno-, or molecular-targeted therapy within the past 4 weeks before registration or concomitantly with this trial. This restriction does not apply to bisphosphonates.
  11. Patients unable to comply with the protocol according to the discretion of the investigator or sub-investigators
  12. Current alcohol abuse or drug abuse according to the discretion of the investigator
  13. Patients who are inappropriate for this trial by the discretion of investigator or sub-investigators (e.g. uncontrolled diabetes mellitus, evidence of serious active infection, medically significant abnormal laboratory finding, etc.)

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): NCT01348347


Locations
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Japan
1230.15.001 National Cancer Center Hospital,
Chuo-ku, Tokyo, Japan
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01348347    
Other Study ID Numbers: 1230.15
First Posted: May 5, 2011    Key Record Dates
Results First Posted: August 6, 2018
Last Update Posted: August 6, 2018
Last Verified: August 2018