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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00824408
• Date of registration: 15/01/2009
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim
• Public title: Trial of BI 6727 (Volasertib) Monotherapy and BI 6727 in Combination With Pemetrexed Compared to Pemetrexed Monotherapy in Advanced NSCLC
• Scientific 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
• Date of first enrolment: March 2009
• Target sample size: 143
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00824408
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

Australia, Bahamas, Canada

Contacts

• Name: Boehringer Ingelheim
• Affiliation: Boehringer Ingelheim

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Carcinoma, Non-Small-Cell Lung

Intervention(s)

Drug: pemetrexed

Drug: BI 6727

Primary Outcome(s)

Progression Free Survival (PFS) Time From the Date of Randomization to Date of Disease Progression or Death, Whichever Occurred First. [Time Frame: From randomization until disease progression or death]

Secondary Outcome(s)

Occurrence and Intensity of AEs Graded According to CTCAE. [Time Frame: From first drug infusion until 21 days after last drug infusion, up to 1100 days]

Vss of Volasertib [Time Frame: 5 minutes (min) before the start of Volasertib infusion and 1 hour (h), 2h, 4h, 24h, 168h and 336h after the start of Volasertib infusion]

Frequency of Patients With Possible Clinically Significant Abnormalities [Time Frame: From first drug infusion until 21 days after last drug infusion, up to 1100 days]

Overall Survival (OS) [Time Frame: From randomization until time of death]

Objective Tumor Response, Defined as Complete Response (CR), and Partial Response (PR), Evaluated According to RECIST Criteria. [Time Frame: From first drug infusion until 21 days after last drug infusion, up to 1100 days]

Cmax of Pemetrexed [Time Frame: 5 minutes before pemetrexed infusion, at the end of the infusion and 1.5 hours (h), 2.5h, 4.5h and 25.5h after the end of pemetrexed infusion]

Duration of Overall Response [Time Frame: From the time measurement criteria were met for CR or PR (whichever was first recorded) until the first date that recurrent or progressive disease was objectively documented]

Occurence of DLT [Time Frame: Patients were treated for repeated 21-day treatment cycles until disease progression or intolerability of the trial drug, whichever occurred first.]

Vss of Pemetrexed [Time Frame: 5 minutes before pemetrexed infusion, at the end of the infusion and 1.5 hours (h), 2.5h, 4.5h and 25.5h after the end of pemetrexed infusion]

CL of Pemetrexed [Time Frame: 5 minutes before pemetrexed infusion, at the end of the infusion and 1.5 hours (h), 2.5h, 4.5h and 25.5h after the end of pemetrexed infusion]

Cmax of Volasertib [Time Frame: 5 minutes (min) before the start of Volasertib infusion and 1 hour (h), 2h, 4h, 24h, 168h and 336h after the start of Volasertib infusion]

Total Clearance (CL) of Volasertib [Time Frame: 5 minutes (min) before the start of Volasertib infusion and 1 hour (h), 2h, 4h, 24h, 168h and 336h after the start of Volasertib infusion]

Secondary ID(s)

1230.5

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 20/09/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00824408