Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
Exploratory evaluation of safety, tolerability, pharmacokinetics (PK), maximum tolerated dose (MTD), and efficacy of BI 2536 administered in combination with pemetrexed
Interventions
DRUGBI 2536
DRUGPemetrexed
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
1. Pathologic or cytologic confirmed diagnosis of NSCLC 2. Recurrent, advanced or metastatic NSCLC that had progressed following 1 prior chemotherapy regimen for advanced disease. Patients could have received prior adjuvant chemotherapy as long as the disease free interval was longer than 1 year. 3. Measurable disease by 1 or more techniques (CT, MRI) according to RECIST criteria 4. Male or female aged 18 years or older 5. Life expectancy of at least 3 months 6. Eastern Cooperative Oncology Group (ECOG) performance score 0-2 7. Written informed consent that was consistent with International Conference on Harmonization (ICH) - Good Clinical Practice (GCP) guidelines
Exclusion criteria
1. Treatment with an investigational drug in another clinical study within the 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 28 days prior to Day 1 of treatment period 1 of this trial 3. Any persisting toxicities that were deemed to be clinically significant from the previous therapy 4. Received more than 1 prior chemotherapy regimen for advanced disease (not including prior adjuvant therapy). Patients could have received prior epidermal growth factor receptor tyrosine kinase inhibitors 5. 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 had received prior whole brain irradiation and whose brain metastases were stable according to the criteria above were not 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 have limited compliance with trial requirement or which were considered relevant for the evaluation of the efficacy or safety of the trial drug 9. Unable or unwilling to interrupt concomitant administration of NSAIDS 5 days prior to the day of and up to 2 days after the administration of pemetrexed 10. Received prior therapy with pemetrexed 11. Absolute neutrophil count (ANC) ≤1 500/μL, platelet count ≤100 000/μL, or haemoglobin \<9 mg/dL 12. Total bilirubin \>1.5 mg/dL (26 μmol/L), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥2.5 x the upper limit of normal (ULN), except in cases of known liver metastasis where a maximum 5 x ULN was acceptable 13. Serum creatinine level \>1.5 mg/dL and or creatinine clearance \<45 mL/min 14. Sexually active and unwilling to use a medically acceptable method of contraception 15. Pregnancy or breast feeding 16. Known or suspected active alcohol or drug abuse 17. Unable to comply with the protocol 18. Any known hypersensitivity to the trial drugs or their excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) of BI 2536 in combination with pemetrexed | up to 3 weeks | by occurrence of dose limiting toxicities (DLT) |
| Number of patients with adverse events during combination therapy | up to 20 weeks | according to common terminology criteria for adverse events (CTCAE) 3.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | up to 2 years | — |
| Overall survival | up to 2 years | — |
| Objective tumor response after combination therapy | up to 20 weeks | according to Response Evaluation Criteria in Solid Tumours (RECIST) |
| Change in Eastern Cooperative Oncology Group (ECOG) performance score | baseline, up to 1 year | — |
| Number of patients with abnormal laboratory findings | up to 20 weeks | — |
| Duration of objective tumor response after combination therapy | up to 1 year | — |
Outcome results
None listed