Trial of BI 6727 (Volasertib) Monotherapy and BI 6727 in Combination With Pemetrexed Compared to Pemetrexed Monotherapy in Advanced NSCLC
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: pemetrexed; pemetrexed; BI 6727
Intervention description: 500 mg/m^2 i.v. on day 1 of 21 day cycle; 500 mg/m^2 i.v. on day 1 of 21 day cycle; BI 6727 i.v. on day 1 of a 21 day cycle
Intervention MeSH terms: Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 143.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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