Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

BI 2536

Boehringer Ingelheim

The trial will be performed to evaluate whether BI 2536 may be effective in the treatment of advanced or metastatic NSCLC of stage IIIB or IV in patients who relapsed after or failed first-line therapy. A secondary aim is to identify the most suitable dosage schedule for the further Phase II and III clinical programme of BI 2536. To achieve this objective two dosage schedules are compared.

Efficacy and Safety of BI 2536 in Advanced or Metastatic Non Small Cell Lung Cancer

An Open, Randomised Clinical Phase II Trial to Investigate the Efficacy, Safety and Pharmacokinetics of a Single Dose of 200 mg of i.v. BI 2536 in Comparison to 50 mg of i.v. BI 2536 Administered on Days 1, 2 and 3 in Patients With Advanced or Metastatic Non Small Cell Lung Cancer

The best overall response was the best response recorded from start of treatment until the participant progressed, received any other anti-tumour therapy, died or until the individual participant's end of trial. Number of participants with 'Objective tumour response evaluated according to RECIST 1.0 by central review of the tumour images = Yes' are reported. Objective response is complete response (disappearance of all target lesions) or partial response (at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter). Changes in tumour measurements were confirmed by repeat assessments that had to be performed 6 weeks after the criteria for response had been first met.

Progression-free survival defined as time from date of randomisation until "date of imaging indicating progressive disease (PD) as assessed by the independent central imaging review (according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0)" or "date of investigator assessment of clinical progression" or "date of progressive disease recorded during the follow-up period" or "death date", whatever comes first. Participants without documented progression at the time of analysis were censored at the date of the last visit.

Per RECIST version 1.0 for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): PD, At least a 20% increase in the sum of the longest diameter (SoD) of target lesions taking as reference the smallest SoD of target lesions recorded since the treatment started or the appearance of one or more new lesions.

Overall survival defined as time from date of randomisation until date of death from any cause. Participants alive at the time of analysis were censored at the date of the last trial visit or last date of follow-up, whatever came last.

For participants who showed an overall tumour response of complete response (CR, disappearance of all target lesions) or partial response (PR, at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter), 'duration of overall response' was defined as the time from the first date where 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 the treatment started). Tumour response was evaluated based on local radiological images according to RECIST version 1.0 (agreed upon by independent review). The number of participants with an CR or PR who experienced the event 'recurrent or PD' is reported instead of the time-to-event data with unit of time as the number analyzed was too small to perform a Kaplan-Meier analysis.

The best overall response was the best response recorded from start of treatment until the participant progressed, received any other anti-tumour therapy, died or until the individual participant's end of trial. 'Objective tumour response evaluated according to RECIST 1.0 by investigator' is 'Yes' if the best overall response is either complete response (CR, disappearance of all target lesions) or partial response (PR, at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter). Otherwise it is 'No'. To be assigned a status of 'partial response' or 'complete response', changes in tumour measurements were confirmed by repeat assessments that had to be performed six weeks after the criteria for response had been first met.

Number of participants with 'Objective tumour response evaluated according to RECIST 1.0 by investigator = Yes' are reported.

Time to deterioration for cough \[days\] was defined as the time from randomization to deterioration in score for the symptom 'cough'. Participants were considered to have deteriorated if a 10-point increase from the baseline score at any time point after baseline was observed. Participants who died before deteriorating were analyzed as having deteriorated at the time of death. Participants with disease progression without deterioration in score were censored at the time of the last scale measurement. Participants with no QoL assessments were censored at day 1. The score for symptom 'cough' was based on Question 1 on the lung cancer module QLQ LC13 of the EORTC QLQ C30 Version 3.0. A linear transformation was used to standardize the raw scores, so that scores range from 0 to 100. A high score represents a higher ("worse") level of the symptom 'cough'.

Time to deterioration for dyspnoea \[days\] was defined as the time from randomization to deterioration in score for the symptom 'dyspnoea'. Participants were considered to have deteriorated if a 10-point increase from the baseline score at any time point after baseline was observed. Participants who died before deteriorating were analyzed as having deteriorated at the time of death. Participants with disease progression without deterioration in score were censored at the time of the last scale measurement. Participants with no QoL assessments were censored at day 1. The score for symptom 'dyspnoea' was based on the composite of Questions 3-5 on the lung cancer module QLQ LC13 of the EORTC QLQ C30 Version 3.0. A linear transformation was used to standardize the raw scores, so that scores range from 0 to 100. A high score represents a higher ("worse") level of the symptom 'dyspnoea'.

Time to deterioration for pain \[days\] was defined as the time from randomization to deterioration in score for the symptom 'pain'. Participants were considered to have deteriorated if a 10-point increase from the baseline score at any time point after baseline was observed. Participants who died before deteriorating were analyzed as having deteriorated at the time of death. Participants with disease progression without deterioration in score were censored at the time of the last scale measurement. Participants with no QoL assessments will be censored at day 1. The score for symptom 'pain' was based on the composite of Questions 9 and 19 of the EORTC QLQ C30 Version 3.0. A linear transformation was used to standardize the raw scores, so that scores range from 0 to 100. A high score represents a higher ("worse") level of the symptom 'pain'.

BI 2536 plasma concentrations after intravenous infusion of 200 milligram BI 2536 on day 1 in treatment course 1. Geometric Coefficient of Variation reported in percentage \[%\].

BI 2536 plasma concentrations after intravenous infusion of 50 / 60 milligram BI 2536 on day 1 in treatment course 1. Geometric Coefficient of Variation reported in percentage \[%\].

Number of participants with adverse events categorized by "common terminology criteria for adverse events (CTCAE) grades (version 3.0)" are reported.

Dose limiting toxicity was defined as drug related common terminology criteria for adverse events (CTCAE) grade 3 or greater non haematological toxicity (excluding untreated nausea, vomiting or diarrhoea) or drug related CTCAE grade 4 neutropenia for seven or more days and / or complicated by infection or CTCAE grade 4 thrombocytopenia. Number of participants with DLT is reported.

Number of participants with neutropenia of common terminology criteria for adverse events (CTCAE) grade 3 or 4.

Number of participants with thrombocytopenia of common terminology criteria for adverse events (CTCAE) grade 3 or 4.

Change from baseline in systolic/diastolic blood pressure at individual participant's end-of-trial visit.

Change from baseline in pulse rate at individual participant's end-of-trial visit.

All participants who received at least one dose of BI 2536 were included in the safety analyses.

A single dose of 200 mg BI 2536 on day one of each treatment course (comprising 21 days including the day of administration) was administered as an intravenous infusion over a period of 60 minutes. Each participant was planned to receive at least 2 treatment courses, in case of clinical benefit (i.e., at least stable disease and acceptable tolerability) the participants could continue therapy with the trial drug. Trial drug administration was stopped temporarily in case of dose limiting toxicity (DLT). Participants could continue therapy only if recovery from DLT (to CTCAE levels which allowed further therapy) occurred and only with a dose reduced by up to 50 mg. Dose reduction was allowed only once for a participant during the whole trial. If a participant had experienced a second episode of DLT with the reduced dose or the participant had not recovered from DLT then the participant was withdrawn from the trial. A participant who continued therapy with BI 2536 beyond course 2 could be treated with a higher dose in case of non-progression and good tolerability.

200 Milligram (mg) BI 2536 (Day 1)

A single dose of 50 mg BI 2536 on days 1, 2 and 3 of each treatment course (comprising 21 days including the days of administration) was administered as an intravenous infusion over a period of 60 minutes. Each participant was planned to receive at least 2 treatment courses, in case of clinical benefit (i.e., at least stable disease and acceptable tolerability) the participants could continue therapy with the trial drug. Trial drug administration was stopped temporarily in case of dose limiting toxicity (DLT). Participants could continue therapy only if recovery from DLT (to CTCAE levels which allowed further therapy) occurred and only with a dose reduced by up to 10 mg. Dose reduction was allowed only once for a participant during the whole trial. If a participant had experienced a second episode of DLT with the reduced dose or the participant had not recovered from DLT then the participant was withdrawn from the trial. A participant who continued therapy with BI 2536 beyond course 2 could be treated with a higher dose in case of non-progression and good tolerability.

50 Milligram BI 2536 (Day 1 - Day 3)

After implementation of protocol amendment 2 a single dose of 60 mg BI 2536 on days 1, 2 and 3 of each treatment course (comprising 21 days including the days of administration) was administered as an intravenous infusion over a period of 60 minutes. Each participant was planned to receive at least 2 treatment courses, in case of clinical benefit (i.e., at least stable disease and acceptable tolerability) the participants could continue therapy with the trial drug. Trial drug administration was stopped temporarily in case of dose limiting toxicity (DLT). Participants could continue therapy only if recovery from DLT (to CTCAE levels which allowed further therapy) occurred and only with a dose reduced by up to 10 mg. Dose reduction was allowed only once for a participant during the whole trial. If a participant had experienced a second episode of DLT with the reduced dose or the participant had not recovered from DLT then the participant was withdrawn from the trial. A participant who continued therapy with BI 2536 beyond course 2 could be treated with a higher dose in case of non-progression and good tolerability.

60 Milligram BI 2536 (Day 1 - Day 3)

A single dose of 50 mg or 60 mg (following implementation of protocol amendment 2) on days 1, 2 and 3 of each treatment course (comprising 21 days including the days of administration) was administered as an intravenous infusion over a period of 60 minutes. Each participant was planned to receive at least 2 treatment courses, in case of clinical benefit (i.e., at least stable disease and acceptable tolerability) the participants could continue therapy with the trial drug. Trial drug administration was stopped temporarily in case of dose limiting toxicity (DLT). Participants could continue therapy only if recovery from DLT (to CTCAE levels which allowed further therapy) occurred and only with a dose reduced by up to 10 mg. Dose reduction was allowed only once for a participant during the whole trial. If a participant had experienced a second episode of DLT with the reduced dose or the participant had not recovered from DLT then the participant was withdrawn from the trial. A participant who continued therapy with BI 2536 beyond course 2 could be treated with a higher dose in case of non-progression and good tolerability.

Combination of Treatment Group "50 mg BI 2536 (Day 1 - Day 3)" and "60 mg BI 2536 (Day 1 - Day 3)"

A single dose of 200 mg BI 2536 on day one of each treatment course (comprising 21 days including the day of administration) was administered as an intravenous infusion over a period of 60 minutes. Each participant was planned to receive at least 2 treatment courses, in case of clinical benefit (i.e., at least stable disease and acceptable tolerability) the participants could continue therapy. Trial drug administration was stopped temporarily in case of dose limiting toxicity (DLT). Participants could continue therapy only if recovery from DLT occurred and only with a dose reduced by up to 50 mg. Dose reduction was allowed only once for a participant during the whole trial. If a participant had experienced a second episode of DLT with the reduced dose or had not recovered from DLT then the participant was withdrawn from the trial. A participant who continued therapy with BI 2536 beyond course 2 could be treated with a higher dose in case of non-progression and good tolerability.

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated patients who were not randomized.

Boehringer Ingelheim , Call Center

Efficacy of BI 2536 was evaluated by comparing the tumour response rate of the present trial with the tumour response rate published for patients with the same stage of disease treated with placebo. For this, treatment groups 'BI 2536 200 mg' and 'combination of treatment group 50 mg BI 2536 (day 1 - day 3) and 60 mg BI 2536 (day 1 - day 3)' were pooled together and compared to historical placebo.

The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.

Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Central Review of the Tumour Images

Exploratory analysis. No formal hypotheses were tested.

200 Milligram BI 2536 (Day 1)

Combination of 50 mg BI 2536 (Day 1 - Day 3) and 60 mg BI 2536 (Day 1 - Day 3)

Progression Free Survival

Overall Survival

All participants who received at least one application of the BI drug BI 2536 (including treated participants who were not randomized) and who showed an 'overall tumour response of complete response or partial response'.

Duration of Overall Response

All participants who received at least one application of the BI drug BI 2536 (including treated participants who were not randomized) and had at least one post-baseline response evaluation.

Objective Tumour Response Evaluated According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.0) by Investigator

Time-to-deterioration for Symptom Score 'Cough' Assessed on Question 1 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0

Time-to-deterioration for Symptom Score 'Dyspnoea' Assessed on the Composite of Questions 3-5 on the Lung Cancer Module QLQ LC13 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0

Time-to-deterioration for Symptom Score 'Pain' Assessed on the Composite of Questions 9 and 19 of the European Organization for Research and Treatment Quality of Life (QoL) Questionnaire (EORTC QLQ) C30 Version 3.0

0.5 hour post-dose (planned time)

1 hour post-dose (planned time)

2 hour post-dose (planned time)

4 hour post-dose (planned time)

120 hour post-dose (planned time)

The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants that were not randomized.

Plasma concentrations below the limit of quantification were not used.

BI 2536 Plasma Concentrations After Intravenous Infusion of 200 Milligram BI 2536 on Day 1 in Treatment Course 1

23.92 hour post-dose (planned time)

25 hour post-dose (planned time)

47.92 hour post-dose (planned time)

48.5 hour post-dose (planned time)

49 hour post-dose (planned time)

50 hour post-dose (planned time)

52 hour post-dose (planned time)

The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.

Plasma concentrations below the limit of quantification were not used.

BI 2536 Plasma Concentrations After Intravenous Infusion of 50 / 60 Milligram BI 2536 on Day 1 in Treatment Course 1

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Incidence of Adverse Events Categorized by Common Terminology Criteria for Adverse Events (CTCAE) Grades

Incidence of Dose Limiting Toxicity (DLT)

The Treated Set comprised all participants who received at least one application of the BI drug BI 2536 including treated participants who were not randomized.

Participants with laboratory values that were out of range for CTCAE grading and were deemed possible clinically significant abnormal were excluded from the analyses.

Number of Participants With Neutropenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4

Number of Participants With Thrombocytopenia of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4

Change from baseline in systolic blood pressure

Change from baseline in diastolic blood pressure

All participants who received at least one application of the BI drug BI 2536 (including treated patients who were not randomized) and for whom data were collected for this endpoint at the end-of-trial visit.

Spots Global Cancer Trial Database for Efficacy and Safety of BI 2536 in Advanced or Metastatic Non Small Cell Lung Cancer

Trial Identification

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Study Description

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