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Trial of BI 6727 (Volasertib) Monotherapy and BI 6727 in Combination With Pemetrexed Compared to Pemetrexed Monotherapy in Advanced NSCLC

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ClinicalTrials.gov Identifier: NCT00824408
Recruitment Status : Completed
First Posted : January 16, 2009
Results First Posted : September 20, 2016
Last Update Posted : September 20, 2016
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:

The trial objective will be to evaluate whether BI 6727 monotherapy or in combination with pemetrexed may be effective in the treatment of advanced or metastatic NSCLC in patients who relapsed after or failed first-line platinum based therapy.

The secondary objectives are to identify the acceptable dose of BI 6727 in combination with pemetrexed and to characterize the pharmacokinetic profiles of BI 6727 alone. Arm A, BI6727 monotherapy arm is closed to further recruitment.


Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: pemetrexed Drug: BI 6727 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 143 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomised Open-label Phase II Trial of BI 6727 Monotherapy and BI 6727 in Combination With Standard Dose Pemetrexed Compared to Pemetrexed Monotherapy in Second Line Non-small Cell Lung Cancer
Study Start Date : March 2009
Actual Primary Completion Date : September 2012
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: BI 6727 +pemetrexed
BI 6727 plus 500 mg/^m2 pemetrexed i.v. on day 1 of 21 day cycle
Drug: pemetrexed
500 mg/m^2 i.v. on day 1 of 21 day cycle

Drug: BI 6727
BI 6727 i.v. on day 1 of a 21 day cycle

Active Comparator: pemetrexed
500 mg/m^2 i.v. on day 1 of a 21 day cycle
Drug: pemetrexed
500 mg/m^2 i.v. on day 1 of 21 day cycle




Primary Outcome Measures :
  1. Progression Free Survival (PFS) Time From the Date of Randomization to Date of Disease Progression or Death, Whichever Occurred First. [ Time Frame: From randomization until disease progression or death ]

    Disease progression was defined according to the Response Evaluation Criteria in Solid Tumours (RECIST)) criteria. Progression-free survival time was calculated as the duration from the date of randomization to the date of disease progression or death, whichever occured first. For patients with known date of progression (or death): PFS [days] = min (date of progression, date of death) - date of randomization + 1 day. For patients without progression or death, PFS was censored at the last imaging date that showed no disease progression: PFS [days, censored] = date of last imaging showing no progression - date randomization + 1 day.

    The number of participants analysed displays the number of patients with an event (progression).



Secondary Outcome Measures :
  1. Objective Tumor Response, Defined as Complete Response (CR), and Partial Response (PR), Evaluated According to RECIST Criteria. [ Time Frame: From first drug infusion until 21 days after last drug infusion, up to 1100 days ]
    Objective tumor response, defined as complete response (CR), and partial response (PR), evaluated according to RECIST criteria. Evaluation of target lesions: Complete Response (CR): disappearance of all target lesions. Partial Response (PR): ≥30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Evaluation of nontarget lesions: Complete Response (CR): disappearance of all nontarget lesions.

  2. Overall Survival (OS) [ Time Frame: From randomization until time of death ]
    Overall survival (OS) was defined as the duration of time from randomization to time of death.

  3. Duration of Overall Response [ Time Frame: From the time measurement criteria were met for CR or PR (whichever was first recorded) until the first date that recurrent or progressive disease was objectively documented ]
    The duration of overall response was measured from the time measurement criteria were met for CR or PR (whichever was first recorded) until the first date that recurrent or progressive disease (PD) was objectively documented (taking as reference for PD the smallest measurements recorded since treatment began). The duration of overall CR was measured from the time measurement criteria were first met for CR until the first date that recurrent disease was objectively documented. Duration of disease control is presented here.

  4. Occurrence and Intensity of AEs Graded According to CTCAE. [ Time Frame: From first drug infusion until 21 days after last drug infusion, up to 1100 days ]
    All patients were carefully monitored during and after each treatment cycle. Adverse events (AEs) were recorded and were graded according to the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE).

  5. Occurence of DLT [ Time Frame: Patients were treated for repeated 21-day treatment cycles until disease progression or intolerability of the trial drug, whichever occurred first. ]

    Occurence of Dose-limiting toxicity (DLT). A DLT was defined as one or more of the following:

    • treatment-related CTCAE Grade 3 or 4 nonhematological toxicity (except emesis or diarrhea responding to supportive treatment).
    • treatment-related CTCAE Grade 4 neutropenia for ≥7 days and/or complicated by infection.
    • CTCAE Grade 4 thrombocytopenia.

  6. Frequency of Patients With Possible Clinically Significant Abnormalities [ Time Frame: From first drug infusion until 21 days after last drug infusion, up to 1100 days ]
    Frequency of patients with possible clinically significant abnormalities

  7. Cmax of Volasertib [ Time Frame: 5 minutes (min) before the start of Volasertib infusion and 1 hour (h), 2h, 4h, 24h, 168h and 336h after the start of Volasertib infusion ]
    Cmax - maximum measured concentration of volasertib in plasma.

  8. Total Clearance (CL) of Volasertib [ Time Frame: 5 minutes (min) before the start of Volasertib infusion and 1 hour (h), 2h, 4h, 24h, 168h and 336h after the start of Volasertib infusion ]
    CL - total clearance of volasertib in plasma after IV administration

  9. Vss of Volasertib [ Time Frame: 5 minutes (min) before the start of Volasertib infusion and 1 hour (h), 2h, 4h, 24h, 168h and 336h after the start of Volasertib infusion ]
    Vss - apparent volume of distribution at steady state following IV administration of volasertib

  10. Cmax of Pemetrexed [ Time Frame: 5 minutes before pemetrexed infusion, at the end of the infusion and 1.5 hours (h), 2.5h, 4.5h and 25.5h after the end of pemetrexed infusion ]
    Cmax - maximum measured concentration of pemetrexed in plasma

  11. CL of Pemetrexed [ Time Frame: 5 minutes before pemetrexed infusion, at the end of the infusion and 1.5 hours (h), 2.5h, 4.5h and 25.5h after the end of pemetrexed infusion ]
    CL - total clearance of pemetrexed in plasma after IV administration

  12. Vss of Pemetrexed [ Time Frame: 5 minutes before pemetrexed infusion, at the end of the infusion and 1.5 hours (h), 2.5h, 4.5h and 25.5h after the end of pemetrexed infusion ]
    Vss - apparent volume of distribution at steady state following IV administration of pemetrexed



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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. Pathologic or cytologic confirmed diagnosis of NSCLC
  2. Recurrent, advanced or metastatic NSCLC that has progressed following one prior platinum based chemotherapy regimen (not counting adjuvant or neoadjuvant chemotherapy if completed more than 12 months prior to platinum based therapy)
  3. Patients who are eligible for pemetrexed as second line chemotherapy
  4. Measurable disease by one or more techniques (CT, MRI) according to RECIST
  5. Patients aged 18 years or older
  6. Life expectancy of at least three (3) months
  7. Eastern Cooperative Oncology Group (ECOG) performance Score 0-2
  8. Written informed consent that is consistent with ICH-GCP guidelines and local legislation

Exclusion criteria:

  1. Treatment with an investigational drug in another clinical study within the past 28 days prior to the start of therapy or concomitantly with this study
  2. Anti-cancer therapy for NSCLC (except radiotherapy for palliative reasons) within the past 28 days prior to Treatment Day 1 of Cycle 1 of this trial
  3. Any persisting toxicities which are deemed to be clinically significant from the previous therapy
  4. Patients who have received more than one prior chemotherapy regimen for advanced disease (not including prior adjuvant therapy). Patients may have received prior epidermal growth factor receptor tyrosine kinase inhibitors.
  5. Patients who are unwilling or unable to take folic acid and vitamin B12 supplementation
  6. Active brain metastases (stable for <28 days, symptomatic, or requiring concurrent steroids). Patients who have received prior whole brain irradiation and whose brain metastases are stable according to the criteria above will not be excluded.
  7. Other active malignancy diagnosed within the past 3 years (other than non melanomatous skin cancer and cervical intraepithelial neoplasia)
  8. Concomitant intercurrent illnesses including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situation that would limit compliance with trial requirement or which are considered relevant for the evaluation of the efficacy or safety of the trial drug
  9. Patients unable or unwilling to interrupt concomitant administration of NSAIDS 5 days prior to, the day of and 2 days after the administration of pemetrexed, with the exception of lose dose aspirin 81mg daily
  10. Patients who have received prior therapy with pemetrexed
  11. Absolute neutrophil count (ANC) less than 1,500/mm3
  12. Platelet count less than 100,000/mm3
  13. Hemoglobin <90g/L
  14. Total bilirubin >26µmol/L
  15. Alanine amino transferase (ALT) and/or aspartate amino transferase (AST) less than 2.5 X ULN, except in case of known liver metastasis where maximum 5 X ULN is acceptable
  16. Serum creatinine level >133µmol/L and/or creatinine clearance (measured or calculated) <45 ml/min
  17. Clinically relevant QTc prolongation
  18. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
  19. Pregnancy or breast feeding
  20. Known or suspected active alcohol or drug abuse
  21. Patients unable to comply with the protocol
  22. Any known hypersensitivity to the trial drugs or their excipients
  23. Patients with NSCLC of confirmed Squamous histology

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): NCT00824408


Locations
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Bahamas
1230.5.00118 Boehringer Ingelheim Investigational Site
Nassau, Bahamas
Canada, Alberta
1230.5.00104 Boehringer Ingelheim Investigational Site
Edmonton, Alberta, Canada
Canada, British Columbia
1230.5.00114 Boehringer Ingelheim Investigational Site
Kelowna, British Columbia, Canada
1230.5.00109 Boehringer Ingelheim Investigational Site
Surrey, British Columbia, Canada
1230.5.00107 Boehringer Ingelheim Investigational Site
Vancouver, British Columbia, Canada
Canada, Ontario
1230.5.00105 Boehringer Ingelheim Investigational Site
Hamilton, Ontario, Canada
1230.5.00119 Boehringer Ingelheim Investigational Site
Kitchener, Ontario, Canada
1230.5.00116 Boehringer Ingelheim Investigational Site
Oshawa, Ontario, Canada
1230.5.00108 Boehringer Ingelheim Investigational Site
Ottawa, Ontario, Canada
1230.5.00110 Boehringer Ingelheim Investigational Site
Toronto, Ontario, Canada
Canada, Quebec
1230.5.00102 Boehringer Ingelheim Investigational Site
Montreal, Quebec, Canada
1230.5.00106 Boehringer Ingelheim Investigational Site
Montreal, Quebec, Canada
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: NCT00824408     History of Changes
Other Study ID Numbers: 1230.5
First Posted: January 16, 2009    Key Record Dates
Results First Posted: September 20, 2016
Last Update Posted: September 20, 2016
Last Verified: July 2016
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors