Carcinoma, Small Cell
Conditions
Brief summary
Open label, uncontrolled Phase II trial to assess the efficacy and safety of BI 2536 in second line treatment in sensitive-relapse SCLC patients.
Interventions
DRUGBI 2536
Intravenous Infusion
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histologically or cytologically confirmed, -sensitive-relapse- SCLC defined by a relapse 60 days or more after cessation of prior first-line chemotherapy. * Patients with at least one measurable lesion, with longest diameter to be recorded as 20 mm or greater. * Life expectancy of at least three months and ECOG performance score of 2 or less and written informed consent that must be consistent with ICH-GCP Guidelines.
Exclusion criteria
* More than one prior regimen of chemotherapy, mixed small cell/large cell or combined small cell histology. * Symptomatic brain metastases or leptomeningeal disease * Patients with ascites, patients who have any other life-threatening illness or organ system dysfunction, or other malignancies diagnosed within the past five (5) years (other than non melanomatous skin cancer) * Absolute neutrophil count (ANC) \<1,500/µl, platelet count \<100,000/µl, or hemoglobin \<9 mg/dl * Total bilirubin \>1.5 x ULN, aspartame amino transferase (AST) and/or alanine amino transferase (ALT) \>2.5 x ULN, or aspartate amino transferase (AST) and/or alanine amino transferase (ALT) \>5 x ULN in case of known liver metastases, serum creatinine \>2.0 mg/dl (\>176 µmol/L, SI Unit equivalent) * Chemo-, hormone- (other than Megace®) or immunotherapy within the past 4 weeks or within less than 4 half-life times of the previous drug prior to treatment with the trial drug * Radiation therapy within the past 2 weeks prior to or during treatment with the trial drug * Patients with any serious active infection (i.e., requiring an IV antibiotic, antifungal, or antiviral agents), patients with known HIV, hepatitis-B or -C infection * Known or suspected active drug or alcohol abuse * Treatment with any other investigational drug within the past 4 weeks or within less than 4 half-life times of the investigational drug * Patients with a known pre-existing coagulopathy or requiring therapeutic anticoagulation with warfarin (Coumadin ®) * Patients with neuropathy (sensory or motor) CTCAE 3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Tumor Response | Scans during screening (day -28 till day 0) and day 1 of every other (even numbered) 21 day treatment cycle. Up to 40 weeks. | Objective tumor response by investigator was assessed for patients who completed at least two courses of BI 2536 treatment. Tumor images from CT (computed tomography) scan and MRI (magnetic resonance imaging) were evaluated using Response evaluation criteria in solid tumors (RECIST) criteria to determine best tumor response. Objective response (OR) was defined as 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From the start of treatment till death or discontinuation, up to 36 weeks. | Overall survival (OS) was reported as number of participants with event. Overall survival is the time from first treatment to death. In case there was no occurrence of death or progression during follow-up, the time was censored. Median survival time was not calculated due to the low number of deaths in the trial. |
| Duration of Overall Response | Scans during screening (day -28 till day 0) and day 1 of every other (even numbered) 21 day treatment cycle. Up to 40 weeks. | The duration of overall objective response (OR) was measured from the time measurement criteria were met for complete response (CR) or partial response (PR) (whichever was first recorded) until the first date that recurrent or progressive disease was objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) or death any cause. OR is defined as either: CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter). |
| Progression Free Survival (PFS) | Scans during screening (day -28 till day 0) and day 1 of every other (even numbered) 21 day treatment cycle. Up to 40 weeks. | Progression free survival (PFS) was defined as the duration of time from start of treatment to time of progression (or death any cause). Patients who did not experience progression or death during the trial were censored at the date of last tumor assessment visit at which the patient was evaluated and did not experience progressive disease. Patients who dropped out before any evaluation of response, radiological, clinical, or pathological, were censored at the start of treatment. Progressive Disease (PD) was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. |
| Number of Participants With Dose Limiting Toxicity | From the start of treatment till the last treatment + 21 days, up to 36 weeks. | Number of Participants with Dose Limiting Toxicity. Dose limiting toxicity was defined as: * drug related CTCAE Grade 3 or greater non-hematological toxicity (excluding untreated nausea, vomiting or diarrhea) * drug related CTCAE Grade 4 neutropenia for 7 or more days or complicated by infection * CTCAE Grade 4 thrombocytopenia. |
| Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | From the start of treatment till the last treatment + 21 days, up to 36 weeks. | Number of participants with an increase in common terminology criteria (CTC) Grade classification for hematological and clinical chemistry laboratory measures. Changes from Baseline in laboratory measures were classified according to CTC Grades 1-4. Results summarizes the number of patients who had a change in laboratory value that represented an increase in CTC Grade classification during the study (based on maximum Grade). |
| Occurrence and Intensity of Adverse Events Graded According to CTCAE | From the start of treatment till the last infusion + 21 days, up to 36 weeks. | Occurrence and intensity of adverse events graded according to common terminology criteria of adverse event (CTCAE) version 3.0. |
Countries
Canada, United States
Participant flow
Recruitment details
This is an open-label Phase II trial to investigate the efficacy, safety, and pharmacokinetics of a single dose of 200 mg i.v. BI 2536 administered every 21 days in patients with sensitive relapse small cell lung cancer using an uncontrolled, Gehan two-stage trial design with an early stopping rule based on patient response.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| BI 2536 200 mg Patients received a single intravenous infusion of 200 milligram (mg) BI 2536 on day 1 of each 21 day treatment cycle. Beyond the second treatment cycle patients may either be treated with the original dose or may receive a higher dose in case of clinical benefit and good tolerability. BI 2536 dosing can be increased in steps of 50 mg. Dose escalations may be repeated after every other course. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Consent withdrawn | 1 |
| Overall Study | Progressive disease | 20 |
| Overall Study | Withdrew, overdose of study treatment | 1 |
Baseline characteristics
| Characteristic | BI 2536 200 mg |
|---|---|
| Age, Continuous | 60.0 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 23 |
| other Total, other adverse events | 21 / 23 |
| serious Total, serious adverse events | 5 / 23 |
Outcome results
Primary
Number of Participants With Objective Tumor Response
Objective tumor response by investigator was assessed for patients who completed at least two courses of BI 2536 treatment. Tumor images from CT (computed tomography) scan and MRI (magnetic resonance imaging) were evaluated using Response evaluation criteria in solid tumors (RECIST) criteria to determine best tumor response. Objective response (OR) was defined as 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).
Time frame: Scans during screening (day -28 till day 0) and day 1 of every other (even numbered) 21 day treatment cycle. Up to 40 weeks.
Population: Treated set (TS): includes all patients who were documented to have taken at least one application of BI 2536. Four patients were excluded from this endpoint due to not having completed two treatment cycles (21 days each).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BI 2536 200 mg | Number of Participants With Objective Tumor Response | Complete response | 0 Participants |
| BI 2536 200 mg | Number of Participants With Objective Tumor Response | Partial response | 0 Participants |
Secondary
Duration of Overall Response
The duration of overall objective response (OR) was measured from the time measurement criteria were met for complete response (CR) or partial response (PR) (whichever was first recorded) until the first date that recurrent or progressive disease was objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) or death any cause. OR is defined as either: CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter).
Time frame: Scans during screening (day -28 till day 0) and day 1 of every other (even numbered) 21 day treatment cycle. Up to 40 weeks.
Population: Analysis of duration of overall response was not conducted, as there were no responders
Secondary
Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures
Number of participants with an increase in common terminology criteria (CTC) Grade classification for hematological and clinical chemistry laboratory measures. Changes from Baseline in laboratory measures were classified according to CTC Grades 1-4. Results summarizes the number of patients who had a change in laboratory value that represented an increase in CTC Grade classification during the study (based on maximum Grade).
Time frame: From the start of treatment till the last treatment + 21 days, up to 36 weeks.
Population: Treated set (TS): includes all patients who were documented to have taken at least one application of BI 2536.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Lymphocytes | CTC Grade 1 | 3 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Lymphocytes | CTC Grade 2 | 4 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Lymphocytes | CTC Grade 3 | 6 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Lymphocytes | CTC Grade 4 | 1 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Lymphocytes | no increase in CTC grade | 9 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Neutrophil | CTC Grade 1 | 0 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Neutrophil | CTC Grade 2 | 4 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Neutrophil | CTC Grade 3 | 6 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Neutrophil | CTC Grade 4 | 11 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Neutrophil | no increase in CTC grade | 2 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Aspartate aminotransferase | CTC Grade 1 | 4 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Aspartate aminotransferase | CTC Grade 2 | 0 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Aspartate aminotransferase | CTC Grade 3 | 2 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Aspartate aminotransferase | CTC Grade 4 | 0 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Aspartate aminotransferase | no increase in CTC grade | 17 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Alanine aminotransferase | CTC Grade 1 | 4 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Alanine aminotransferase | CTC Grade 2 | 1 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Alanine aminotransferase | CTC Grade 3 | 1 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Alanine aminotransferase | CTC Grade 4 | 0 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Alanine aminotransferase | no increase in CTC grade | 17 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Haemoglobin | CTC Grade 1 | 5 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Haemoglobin | CTC Grade 2 | 9 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Haemoglobin | CTC Grade 3 | 1 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Haemoglobin | CTC Grade 4 | 1 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Haemoglobin | no increase in CTC grade | 7 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Platelets | CTC Grade 1 | 10 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Platelets | CTC Grade 2 | 1 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Platelets | CTC Grade 3 | 3 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Platelets | CTC Grade 4 | 1 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Platelets | no increase in CTC grade | 8 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | White blood cell count | CTC Grade 1 | 1 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | White blood cell count | CTC Grade 2 | 8 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | White blood cell count | CTC Grade 3 | 11 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | White blood cell count | CTC Grade 4 | 3 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | White blood cell count | no increase in CTC grade | 0 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Creatinine | CTC Grade 1 | 1 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Creatinine | CTC Grade 2 | 0 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Creatinine | CTC Grade 3 | 0 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Creatinine | CTC Grade 4 | 0 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Creatinine | no increase in CTC grade | 22 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Bilirubin, total | CTC Grade 1 | 0 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Bilirubin, total | CTC Grade 2 | 0 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Bilirubin, total | CTC Grade 3 | 2 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Bilirubin, total | CTC Grade 4 | 0 Participants |
| BI 2536 200 mg | Number of Participants With an Increase in CTC Grade Classification for Hematological and Clinical Chemistry Laboratory Measures | Bilirubin, total | no increase in CTC grade | 21 Participants |
Secondary
Number of Participants With Dose Limiting Toxicity
Number of Participants with Dose Limiting Toxicity. Dose limiting toxicity was defined as: * drug related CTCAE Grade 3 or greater non-hematological toxicity (excluding untreated nausea, vomiting or diarrhea) * drug related CTCAE Grade 4 neutropenia for 7 or more days or complicated by infection * CTCAE Grade 4 thrombocytopenia.
Time frame: From the start of treatment till the last treatment + 21 days, up to 36 weeks.
Population: Treated set (TS): includes all patients who were documented to have taken at least one application of BI 2536.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BI 2536 200 mg | Number of Participants With Dose Limiting Toxicity | 4 Participants |
Secondary
Occurrence and Intensity of Adverse Events Graded According to CTCAE
Occurrence and intensity of adverse events graded according to common terminology criteria of adverse event (CTCAE) version 3.0.
Time frame: From the start of treatment till the last infusion + 21 days, up to 36 weeks.
Population: Treated set (TS): includes all patients who were documented to have taken at least one application of BI 2536.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BI 2536 200 mg | Occurrence and Intensity of Adverse Events Graded According to CTCAE | CTCAE grade 1 | 1 Participants |
| BI 2536 200 mg | Occurrence and Intensity of Adverse Events Graded According to CTCAE | CTCAE grade 2 | 4 Participants |
| BI 2536 200 mg | Occurrence and Intensity of Adverse Events Graded According to CTCAE | CTCAE grade 3 | 8 Participants |
| BI 2536 200 mg | Occurrence and Intensity of Adverse Events Graded According to CTCAE | CTCAE grade 4 | 6 Participants |
| BI 2536 200 mg | Occurrence and Intensity of Adverse Events Graded According to CTCAE | CTCAE grade 5 | 2 Participants |
Secondary
Overall Survival
Overall survival (OS) was reported as number of participants with event. Overall survival is the time from first treatment to death. In case there was no occurrence of death or progression during follow-up, the time was censored. Median survival time was not calculated due to the low number of deaths in the trial.
Time frame: From the start of treatment till death or discontinuation, up to 36 weeks.
Population: Treated set (TS): includes all patients who were documented to have taken at least one application of BI 2536..
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BI 2536 200 mg | Overall Survival | 5 Participants |
Secondary
Progression Free Survival (PFS)
Progression free survival (PFS) was defined as the duration of time from start of treatment to time of progression (or death any cause). Patients who did not experience progression or death during the trial were censored at the date of last tumor assessment visit at which the patient was evaluated and did not experience progressive disease. Patients who dropped out before any evaluation of response, radiological, clinical, or pathological, were censored at the start of treatment. Progressive Disease (PD) was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Scans during screening (day -28 till day 0) and day 1 of every other (even numbered) 21 day treatment cycle. Up to 40 weeks.
Population: Treated set (TS): includes all patients who were documented to have taken at least one application of BI 2536.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 2536 200 mg | Progression Free Survival (PFS) | 43 days |