Trial of BI 6727 (Volasertib) Monotherapy and BI 6727 in Combination With Pemetrexed Compared to Pemetrexed Monotherapy in Advanced NSCLC
- Registration Number
- NCT00824408
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 143
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description pemetrexed pemetrexed 500 mg/m\^2 i.v. on day 1 of a 21 day cycle BI 6727 +pemetrexed BI 6727 BI 6727 plus 500 mg/\^m2 pemetrexed i.v. on day 1 of 21 day cycle BI 6727 +pemetrexed pemetrexed BI 6727 plus 500 mg/\^m2 pemetrexed i.v. on day 1 of 21 day cycle
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Time From the Date of Randomization to Date of Disease Progression or Death, Whichever Occurred First. 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
Name Time Method Frequency of Patients With Possible Clinically Significant Abnormalities From first drug infusion until 21 days after last drug infusion, up to 1100 days Frequency of patients with possible clinically significant abnormalities
Objective Tumor Response, Defined as Complete Response (CR), and Partial Response (PR), Evaluated According to RECIST Criteria. 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.
Overall Survival (OS) From randomization until time of death Overall survival (OS) was defined as the duration of time from randomization to time of death.
Duration of Overall Response 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.
Occurrence and Intensity of AEs Graded According to CTCAE. 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).
Occurence of DLT 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.Total Clearance (CL) of Volasertib 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
Cmax of Pemetrexed 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
Cmax of Volasertib 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.
CL of Pemetrexed 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
Vss of Pemetrexed 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
Vss of Volasertib 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
Trial Locations
- Locations (12)
1230.5.00106 Boehringer Ingelheim Investigational Site
🇨🇦Montreal, Quebec, Canada
1230.5.00118 Boehringer Ingelheim Investigational Site
🇧🇸Nassau, Bahamas
1230.5.00114 Boehringer Ingelheim Investigational Site
🇨🇦Kelowna, British Columbia, Canada
1230.5.00104 Boehringer Ingelheim Investigational Site
🇨🇦Edmonton, Alberta, Canada
1230.5.00109 Boehringer Ingelheim Investigational Site
🇨🇦Surrey, British Columbia, Canada
1230.5.00107 Boehringer Ingelheim Investigational Site
🇨🇦Vancouver, British Columbia, Canada
1230.5.00105 Boehringer Ingelheim Investigational Site
🇨🇦Hamilton, Ontario, Canada
1230.5.00119 Boehringer Ingelheim Investigational Site
🇨🇦Kitchener, Ontario, Canada
1230.5.00102 Boehringer Ingelheim Investigational Site
🇨🇦Montreal, Quebec, 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