Trial of BI 6727 (Volasertib) Monotherapy and BI 6727 in Combination With Pemetrexed Compared to Pemetrexed Monotherapy in Advanced NSCLC

A Randomised Open-label Phase II Trial of BI 6727 Monotherapy and BI 6727 in Combination With Standard Dose Pemetrexed Compared to Pemetrexed Monotherapy in Second Line Non-small Cell Lung Cancer

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.

Inclusion criteria:

1. Pathologic or cytologic confirmed diagnosis of NSCLC
2. Recurrent, advanced or metastatic NSCLC that has progressed following one prior platinum based chemotherapy regimen (not counting adjuvant or neoadjuvant chemotherapy if completed more than 12 months prior to platinum based therapy)
3. Patients who are eligible for pemetrexed as second line chemotherapy
4. Measurable disease by one or more techniques (CT, MRI) according to RECIST
5. Patients aged 18 years or older
6. Life expectancy of at least three (3) months
7. Eastern Cooperative Oncology Group (ECOG) performance Score 0-2
8. Written informed consent that is consistent with ICH-GCP guidelines and local legislation

Exclusion criteria:

1. Treatment with an investigational drug in another clinical study within the past 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 past 28 days prior to Treatment Day 1 of Cycle 1 of this trial
3. Any persisting toxicities which are deemed to be clinically significant from the previous therapy
4. Patients who have received more than one prior chemotherapy regimen for advanced disease (not including prior adjuvant therapy). Patients may have received prior epidermal growth factor receptor tyrosine kinase inhibitors.
5. Patients who are 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 have received prior whole brain irradiation and whose brain metastases are stable according to the criteria above will not be 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 limit compliance with trial requirement or which are considered relevant for the evaluation of the efficacy or safety of the trial drug
9. Patients unable or unwilling to interrupt concomitant administration of NSAIDS 5 days prior to, the day of and 2 days after the administration of pemetrexed, with the exception of lose dose aspirin 81mg daily
10. Patients who have received prior therapy with pemetrexed
11. Absolute neutrophil count (ANC) less than 1,500/mm3
12. Platelet count less than 100,000/mm3
13. Hemoglobin <90g/L
14. Total bilirubin >26µmol/L
15. Alanine amino transferase (ALT) and/or aspartate amino transferase (AST) less than 2.5 X ULN, except in case of known liver metastasis where maximum 5 X ULN is acceptable
16. Serum creatinine level >133µmol/L and/or creatinine clearance (measured or calculated) <45 ml/min
17. Clinically relevant QTc prolongation
18. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
19. Pregnancy or breast feeding
20. Known or suspected active alcohol or drug abuse
21. Patients unable to comply with the protocol
22. Any known hypersensitivity to the trial drugs or their excipients
23. Patients with NSCLC of confirmed Squamous histology