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

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00824408
• Other study ID #: 1230.5
• Status: Active, not recruiting
• Phase: Phase 2
• First received: January 15, 2009
• Last updated: October 7, 2014
• Start date: March 2009
• Est. completion date: January 2015

Study information

• Verified date: October 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 143
• Est. completion date: January 2015
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• pemetrexed
500 mg/m^2 i.v. on day 1 of 21 day cycle
• pemetrexed
500 mg/m^2 i.v. on day 1 of 21 day cycle
• BI 6727
BI 6727 i.v. on day 1 of a 21 day cycle

Locations

Country	Name	City	State
Bahamas	1230.5.00118 Boehringer Ingelheim Investigational Site	Nassau
Canada	1230.5.00104 Boehringer Ingelheim Investigational Site	Edmonton	Alberta
Canada	1230.5.00105 Boehringer Ingelheim Investigational Site	Hamilton	Ontario
Canada	1230.5.00114 Boehringer Ingelheim Investigational Site	Kelowna	British Columbia
Canada	1230.5.00119 Boehringer Ingelheim Investigational Site	Kitchener	Ontario
Canada	1230.5.00102 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1230.5.00106 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1230.5.00116 Boehringer Ingelheim Investigational Site	Oshawa	Ontario
Canada	1230.5.00108 Boehringer Ingelheim Investigational Site	Ottawa	Ontario
Canada	1230.5.00109 Boehringer Ingelheim Investigational Site	Surrey	British Columbia
Canada	1230.5.00110 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1230.5.00107 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Bahamas,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival time (PFS) from the date of randomization to the earlier date of disease progression or death.		12 months	No
Secondary	Objective tumor response, defined as complete response (CR), and partial response (PR), evaluated according to RECIST; Overall survival; Duration of overall response; Pharmacokinetic characteristics of BI 6727 and pemetrexed;occurence and intensity of AE		8 months	No