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BI 6727 (Volasertib) in Combination With Cisplatin or Carboplatin in Patients With Advanced or Metastatic Solid Tumour

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ClinicalTrials.gov Identifier: NCT00969761
Recruitment Status : Completed
First Posted : September 1, 2009
Results First Posted : January 31, 2019
Last Update Posted : January 31, 2019
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:

The primary objective of this trial is to identify the maximum tolerated dose (MTD) of BI 6727 therapy in terms of drug-related adverse events when combined with a platinum therapy (cisplatin or carboplatin).

Secondary objectives are the collection of overall safety and antitumour efficacy data and the determination of the pharmacokinetic profile of BI 6727 combination treatment with cisplatin and carboplatin.


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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Trial of BI 6727 in Combination With Cisplatin or Carboplatin in Patients With Advanced or Metastatic Solid Tumors
Study Start Date : August 2009
Actual Primary Completion Date : November 2011
Actual Study Completion Date : February 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: A. BI 6727-cisplatin
patient to receive 3-weekly infusion escalating dose of BI 6727 combined to cisplatin
Drug: BI 6727
low to high dose

Experimental: B. BI 6727-carboplatin
patient to receive 3-weekly infusion escalating dose of BI 6727 combined to carboplatin
Drug: BI-6727
Low to high dose (administered every 3 weeks). Depending on the toxicities observed, intermediary dose levels may be added




Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: 3 weeks ]

    The maximum tolerated dose (MTD) was defined as the highest dose studied for which the incidence of DLT was less than 33% (i.e. 1/6 patients) during the first cycle, for Volasertib in combination with cisplatin or carboplatin.

    0=not maximum tolerated dose, 1=was maximum tolerated dose.



Secondary Outcome Measures :
  1. Percentage of Participants With Dose Limiting Toxicities [ Time Frame: 3 weeks ]
    Percentage of participants with dose limiting toxicities (DLTs) during the first treatment cycle.

  2. Objective Response Rate [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]

    Objective response was defined as the proportion of participants having at least a best response of complete response (CR) or partial response (PR) determined based on RECIST criteria, version 1.0 (V1.0).

    Tumour response was documented using appropriate techniques


  3. Duration of Objective Response [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]

    Duration of objective response was defined as the time from first documented confirmed complete response (CR) or partial response (PR) to first evidence of progressive disease (PD) or death from any cause, whichever occurred first, determined based on RECIST V1.0 criteria.

    Tumour response was documented using appropriate techniques


  4. Best Overall Response [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]
    Best overall response was defined as the best response obtained since the start of study treatment until disease progression, determined based on RECIST V1.0 criteria.

  5. Disease Control Rate [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]
    Percentage of participants with confirmed disease control, defined as the proportion of patients with a best overall response of at least stable disease (SD), determined based on RECIST V1.0 criteria.

  6. Duration of Disease Control [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]
    Duration of Disease control was defined as the time from the start of study treatment to the time of disease progression or death, whichever occurred first.

  7. Progression-free Survival [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]
    Progression-free survival based on RECIST V1.0 criteria was defined as the time from start of treatment to the date of evidence of progressive disease (PD) or death from any cause, whichever occurred first.

  8. Incidence and Intensity of Adverse Events According to CTCAE Version 3.0 [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]
    Incidence and intensity of adverse events according to common terminology criteria for adverse events (CTCAE) version 3.0

  9. Percentage of Participants With Serious Adverse Events [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]
    Percentage of participants with serious adverse events (AEs)

  10. Percentage of Participants With Significant Adverse Events [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]

    Percentage of participants with significant adverse events (AEs): dose limiting toxicity (DLT) was defined as significant AE.

    DLTs (i.e. significant AEs) per protocol were:

    • drug related CTCAE grade 3 or 4 non haematological toxicity (except vomiting or diarrhoea responding to supportive treatment and ototoxicity)
    • drug related CTCAE grade 4 neutropenia for seven or more days and / or complicated by infection
    • drug related CTCAE Grade 4 thrombocytopenia
    • drug related febrile neutropenia grade 3 (ANC<1000/mm³ and fever≥ 38.5°C)

  11. Total Plasma Clearance After Intravascular Administration (CL) [ Time Frame: 1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion ]
    Total plasma clearance after intravascular administration (CL) of Volasertib in combination with cisplatin or carboplatin during treatment cycle 1.

  12. Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss) [ Time Frame: 1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion ]
    Apparent volume of distribution at steady state following intravascular administration (Vss) of Volasertib in combination with cisplatin or carboplatin during treatment cycle 1.

  13. Change From Baseline in Pulse Rate [ Time Frame: Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]
    Change from baseline in pulse rate at last value on treatment

  14. Change From Baseline in Neutrophils [ Time Frame: Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]
    Change from baseline in neutrophils with the maximum value on treatment

  15. Change From Baseline in Platelets [ Time Frame: Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]
    Change from baseline in platelets with the maximum value on treatment

  16. Frequency of Participants (%) With Possible Clinically Significant Abnormalities for Neutrophils [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]
    Frequency of participants (%) with possible clinically significant abnormalities for neutrophils: : defined as neutrophils >=CTCAE grade 2 (CTCAE v3.0), with worsening from baseline. The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).

  17. Frequency of Participants (%) With Possible Clinically Significant Abnormalities for Platelets [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]

    Frequency of participants (%) with possible clinically significant abnormalities for platelets : defined as platelets >=CTCAE grade 2 (based on CTCAE v3.0), with worsening from baseline.

    The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).


  18. Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Platelets Based on Last Value on Treatment [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]

    Percentage of participants with transitions relative to the baseline CTC grade (version 3) for platelets based on last value on treatment.

    Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).


  19. Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Neutrophils Based on Last Value on Treatment [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]

    Percentage of participants with transitions relative to the baseline CTC grade (version 3) for neutrophils based on last value on treatment.

    Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE)


  20. Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Platelets Based on Worst Value on Treatment [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]

    Percentage of participants with transitions relative to the baseline CTC grade (version 3) for platelets based on worst value on treatment.

    Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).


  21. Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Neutrophils Based on Worst Value on Treatment [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]

    Percentage of participants with transitions relative to the baseline CTC grade (version 3) for neutrophils based on worst value on treatment.

    Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE)


  22. Worst CTCAE Grade on Treatment for Platelets [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]
    Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for platelets (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).

  23. Worst CTCAE Grade on Treatment for Neutrophils [ Time Frame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days ]
    Worst Common terminology criteria for adverse events (CTCAE) grade on treatment for neutrophils (CTC version 3). The CTCAE scale measures the severity of adverse events which goes from 1 (mild AE) to 5 (death related AE).



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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, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment
  2. Indication for a treatment with platinum therapy as judged by the investigator
  3. Age 18 years or older
  4. Written informed consent consistent with ICH-GCP and local legislation
  5. ECOG performance score lower or equal 2
  6. Recovery from CTCAE Grade 2 - 4 therapy-related toxicities from previous systemic anti-cancer therapies or radiotherapies (except alopecia grade 2)

Exclusion criteria:

  1. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
  2. Pregnancy or breastfeeding
  3. Active infectious disease or known chronic Hepatitis B/Hepatitis C infection and HIV I/II
  4. Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the past 6 months
  5. Second malignancy currently requiring another anti-cancer therapy
  6. ANC less than 1500 / mm3
  7. Platelet count less than 100 000 / mm3
  8. Bilirubin greater than 1.5 mg / dl (> 26 micromol / L, SI unit equivalent) (except Gilbert's syndrome)
  9. Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal)
  10. Serum creatinine greater than 1.5 mg / dl (> 132 micromol / L, SI unit equivalent) or creatinine clearance <70ml/min (as calculated according to Cockcroft-Gault formula for GFR estimate)
  11. Known history of relevant QT-prolongation, e.g. long QT-syndrome
  12. Pre-existing clinically relevant hearing loss
  13. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
  14. Treatment with other investigational drugs or participation in another clinical interventional trial within the past four weeks before start of therapy or concomitantly with this trial
  15. Systemic anti-cancer therapy or radiotherapy within the past four weeks before start of therapy or concomitantly with this trial. This restriction does not apply to steroids and bisphosphonates.
  16. Patients unable to comply with the protocol
  17. Active alcohol or drug abuse

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): NCT00969761


Locations
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Belgium
1230.6.3201 Boehringer Ingelheim Investigational Site
Bruxelles, Belgium
1230.6.3202 Boehringer Ingelheim Investigational Site
Leuven, Belgium
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: NCT00969761     History of Changes
Other Study ID Numbers: 1230.6
2008-003926-40 ( EudraCT Number: EudraCT )
First Posted: September 1, 2009    Key Record Dates
Results First Posted: January 31, 2019
Last Update Posted: January 31, 2019
Last Verified: August 2018
Additional relevant MeSH terms:
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Cisplatin
Carboplatin
Antineoplastic Agents