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Combination of BI6727 (Volasertib) and BIBF1120 in Solid Tumors

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ClinicalTrials.gov Identifier: NCT01022853
Recruitment Status : Completed
First Posted : December 1, 2009
Results First Posted : July 30, 2018
Last Update Posted : July 30, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
The primary objective of the current study is to investigate the Maximum Tolerated Dose (MTD) in terms of safety and tolerability of BI 6727 in combination with fixed dose BIBF 1120, in patients with advanced or metastatic solid tumours.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: BI 6727 Drug: BIBF 1120 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Phase I Dose Escalation Trial of Intravenous BI 6727 in Combination With Oral BIBF 1120 in Patients With Advanced Solid Tumours With Repeated Administration in Patients With Clinical Benefit
Study Start Date : December 2009
Actual Primary Completion Date : February 2013
Actual Study Completion Date : February 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: BIBF 1120 and BI 6727
Finding Maximum Tolerated Dose of BI 6727 in combination with BIBF 1120
Drug: BI 6727
intravenous each 21 days

Drug: BIBF 1120
oral continuously




Primary Outcome Measures :
  1. Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD). [ Time Frame: 28 days ]

    DLT was defined as:

    1. Drug-related CTCAE (Common Terminology Criteria for Adverse Events) grade 3 or 4 non-haematological toxicity (except untreated vomiting, untreated nausea, or untreated diarrhoea) or
    2. Drug-related CTCAE grade 4 neutropenia for 7 or more days and/or complicated by infection or
    3. CTCAE grade 4 thrombocytopenia

  2. Maximum Tolerated Dose (MTD) of Volasertib in Combination With Nintedanib [ Time Frame: 28 days ]
    The MTD was determined using a 3+3 design with de-escalation. The MTD was defined as the highest dose level at which maximal 1 out of 6 patients experienced DLT in the first course of the escalation nd de-escalation phase. However, all DLT's occurring in the trial were considered for selection of the recommended dose for further development.


Secondary Outcome Measures :
  1. Number of Participants With Drug Related Adverse Events [ Time Frame: From first study drug administration until 28 days after the last administration of any study medication, up to 485 days ]
    Number of participants with investigator-defined drug related adverse events.

  2. Number of Participants With Dose Limiting Toxicities [ Time Frame: From first study drug administration until 28 days after the last administration of any study medication, up to 485 days ]

    Number of participants with dose limiting toxicities (DLTs).

    DLT was defined as:

    1. Drug-related CTCAE grade 3 or 4 non-haematological toxicity (except untreated vomiting, untreated nausea, or untreated diarrhoea) or
    2. Drug-related CTCAE grade 4 neutropenia for 7 or more days and/or complicated by infection or
    3. CTCAE grade 4 thrombocytopenia

  3. Cmax of Volasertib [ Time Frame: 0:05 h before start of Volasertib infusion and 1:00, 2:00, 3:00, 4:00, 8:00 and 24 h after start of Volasertib infusion ]
    Maximum measured concentration (Cmax) in plasma of Volasertib in Cycle 1.

  4. CL of Volasertib [ Time Frame: 0:05 h before start of Volasertib infusion and 1:00, 2:00, 3:00, 4:00, 8:00 and 24 h after start of Volasertib infusion ]
    Total plasma Clearance (CL) of Volasertib in Cycle 1.

  5. Vss of Volasertib [ Time Frame: 0:05 h before start of Volasertib infusion and 1:00, 2:00, 3:00, 4:00, 8:00 and 24 h after start of Volasertib infusion ]
    Volume of distribution at steady state (Vss) of Volasertib in Cycle 1.

  6. Cmax of Nintedanib [ Time Frame: 5 min before Nintedanib administration in the morning and 1:00, 2:00, 3:00, 4:00, 6:00 h after administration on Day 9 ]

    Maximum measured concentration (Cmax) of Nintedanib in Cycle 1.

    400 mg Volasertib + 200 mg Nintedanib group is not displayed due to data only being available for one patient.


  7. AUC(0-6h) of Nintedanib [ Time Frame: 5 min before Nintedanib administration in the morning and 1:00, 2:00, 3:00, 4:00, 6:00 h after administration on Day 9 ]

    Area under the concentration-time curve (AUC) of Nintedanib over the time interval 0 to 6 hours in Cycle 1.

    400 mg Volasertib + 200 mg Nintedanib group is not displayed due to data only being available for one patient.


  8. Tmax of Nintedanib [ Time Frame: 5 min before Nintedanib administration in the morning and 1:00, 2:00, 3:00, 4:00, 6:00 h after administration on Day 9 ]

    Time from dosing to the maximum measured concentration, Cmax, of Nintedanib (tmax) in Cycle 1.

    400 mg Volasertib + 200 mg Nintedanib group is not displayed due to data only being available for one patient.


  9. Number of Patients With Best Overall Response [ Time Frame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment. ]
    Best overall response based on response evaluation criteria in solid tumors (RECIST) version 1.1. Best overall response is defined as the best overall response (complete response, partial response, stable disease, progressive disease or not evaluable) since the start of treatment.

  10. Number of Patients With Objective Response (OR) [ Time Frame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment. ]
    Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.1. OR is defined as complete response (CR) or partial response (PR) as best response throughout the study.

  11. Number of Patients With Disease Control [ Time Frame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment. ]
    Disease control based on response evaluation criteria in solid tumors (RECIST) version 1.1. Disease control is defined as complete response (CR), partial response (PR) or stable disease (SD) as best response throughout the study.

  12. Duration of Disease Control [ Time Frame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment. ]
    Disease control based on response evaluation criteria in solid tumors (RECIST) version 1.1. Patients who had a best overall tumour response of complete response (CR), partial response (PR) or stable disease (SD) were assessed to show disease control.

  13. Progression Free Survival (PFS) [ Time Frame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment. ]
    PFS is defined as the time from start of treatment with study medication to tumour progression or death whichever occurs first. Tumour response was to be documented using appropriate techniques such as magnetic resonance imaging (MRI) or computer tomography (CT).



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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. Patients with confirmed diagnosis of advanced, non resectable and/or metastatic solid tumours, who have failed conventional treatment, and for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment
  2. Age > or = 18 years
  3. European Cooperative Oncology Group performance status < or = 2
  4. Written informed consent in accordance with International Conference on Harmonization -Good Clinical Practice (ICH-GCP) and local legislation
  5. Recovery from Common Terminology Criteria for Adverse Events grade 2-4 therapy-related toxicities from previous systemic anti-cancer therapies or radiotherapy (except alopecia)

Exclusion criteria:

  1. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the trial
  2. Known hypersensitivity to the trial drugs or their excipients
  3. Treatment with any other investigational drug or participation in any other interventional trial within 28 days before first administration of trial drug (BIBF 1120) or concomitantly with this trial
  4. Systemic anti-cancer therapy or radiotherapy within 28 days before start of therapy or concomitantly with this trial. The restriction does not apply to steroids and bisphosphonates
  5. Active infectious disease infection or HIV I/II
  6. Other malignancy currently requiring another anti-cancer therapy
  7. Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the past 6 months
  8. Known inherited predisposition to bleeding or thrombosis
  9. Radiographic evidence of cavitary or necrotic tumours
  10. History of clinically significant haemoptysis within the past 3 months
  11. Centrally located tumours with radiographic evidence (Computed Tomography or Magnetic Resonance Imaging) of local invasion of major blood vessels
  12. Absolute Neutrophil Count (ANC) less than 1.5 x 1000000000/L
  13. Platelets Count (PLT) less than 100 x 1000000000/L
  14. Total bilirubin > upper limit of normal (ULN)
  15. Alaninaminotransferase (ALT) and/or Aspartateaminotransferase (AST) >= 1.5 x ULN (in case of liver metastases: ALT and AST >= 2.5 x ULN)
  16. Serum creatinine > 1.5 mg/dl
  17. Major injuries and/or surgery or bone fracture within 28 days before first administration of trial drug (BIBF 1120), or planned surgical procedures during the trial period
  18. Known history of clinically relevant QT prolongation (e.g. long QT syndrome)
  19. History of severe haemorrhagic or thromboembolic event in the past 6 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis)
  20. Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid < or = 325mg per day)
  21. Active alcohol or drug abuse
  22. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception during the trial
  23. Pregnancy or breast-feeding
  24. Patients unable to comply with the protocol
  25. Uncontrolled hypertension

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): NCT01022853


Locations
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Italy
1230.7.39002 Boehringer Ingelheim Investigational Site
Ancona, Italy
1230.7.39001 Boehringer Ingelheim Investigational Site
Milano, Italy
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim

Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01022853     History of Changes
Other Study ID Numbers: 1230.7
2008-008304-41 ( EudraCT Number: EudraCT )
First Posted: December 1, 2009    Key Record Dates
Results First Posted: July 30, 2018
Last Update Posted: July 30, 2018
Last Verified: October 2017

Additional relevant MeSH terms:
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Nintedanib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action