BI 2536 Second Line Monotherapy in SCLC

Study Overview
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Brief Summary
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Open label, uncontrolled Phase II trial to assess the efficacy and safety of BI 2536 in second line treatment in sensitive-relapse SCLC patients.

Official Title
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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

Conditions
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Carcinoma, Small Cell

Intervention / Treatment
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* Drug: BI 2536


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 2536<br>Total Patients | Drug: BI 2536<br>* Intravenous Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Scans during screening (day -28 till day 0) and day 1 of every other (even numbered) 21 day treatment cycle. Up to 40 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Scans during screening (day -28 till day 0) and day 1 of every other (even numbered) 21 day treatment cycle. Up to 40 weeks. | 
| 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. | From the start of treatment till death or discontinuation, up to 36 weeks. | 
| 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). | Scans during screening (day -28 till day 0) and day 1 of every other (even numbered) 21 day treatment cycle. Up to 40 weeks. | 
| 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. | From the start of treatment till the last infusion + 21 days, up to 36 weeks. | 
| 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. | From the start of treatment till the last treatment + 21 days, up to 36 weeks. | 
| 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). | From the start of treatment till the last treatment + 21 days, up to 36 weeks. |