Clinical trial NCT00824408: Trial of BI 6727 (Volasertib) Monotherapy and BI 6727 in Combination With Pemetrexed Compared to Pemetrexed Monotherapy in Advanced NSCLC
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-01-16
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Progression Free Survival (PFS) Time From the Date of Randomization to Date of Disease Progression or Death, Whichever Occurred First.
timeFrame: From randomization until disease progression or death
Secondary outcomes:
measure: Objective Tumor Response, Defined as Complete Response (CR), and Partial Response (PR), Evaluated According to RECIST Criteria.
timeFrame: From first drug infusion until 21 days after last drug infusion, up to 1100 days
measure: Overall Survival (OS)
timeFrame: From randomization until time of death
measure: Duration of Overall Response
timeFrame: 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
measure: Occurrence and Intensity of AEs Graded According to CTCAE.
timeFrame: From first drug infusion until 21 days after last drug infusion, up to 1100 days
measure: Occurence of DLT
timeFrame: Patients were treated for repeated 21-day treatment cycles until disease progression or intolerability of the trial drug, whichever occurred first.
measure: Frequency of Patients With Possible Clinically Significant Abnormalities
timeFrame: From first drug infusion until 21 days after last drug infusion, up to 1100 days
measure: Cmax of Volasertib
timeFrame: 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
measure: Total Clearance (CL) of Volasertib
timeFrame: 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
measure: Vss of Volasertib
timeFrame: 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
measure: Cmax of Pemetrexed
timeFrame: 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
measure: CL of Pemetrexed
timeFrame: 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
measure: Vss of Pemetrexed
timeFrame: 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
Other outcomes:
Locations:
city: Nassau
country: Bahamas
facility: 1230.5.00118 Boehringer Ingelheim Investigational Site
city: Edmonton
country: Canada
facility: 1230.5.00104 Boehringer Ingelheim Investigational Site
state: Alberta
city: Kelowna
country: Canada
facility: 1230.5.00114 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Surrey
country: Canada
facility: 1230.5.00109 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: 1230.5.00107 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Hamilton
country: Canada
facility: 1230.5.00105 Boehringer Ingelheim Investigational Site
state: Ontario
city: Kitchener
country: Canada
facility: 1230.5.00119 Boehringer Ingelheim Investigational Site
state: Ontario
city: Oshawa
country: Canada
facility: 1230.5.00116 Boehringer Ingelheim Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: 1230.5.00108 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1230.5.00110 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: 1230.5.00102 Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: 1230.5.00106 Boehringer Ingelheim Investigational Site
state: Quebec
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Ellis PM, Leighl NB, Hirsh V, Reaume MN, Blais N, Wierzbicki R, Sadrolhefazi B, Gu Y, Liu D, Pilz K, Chu Q. A Randomized, Open-Label Phase II Trial of Volasertib as Monotherapy and in Combination With Standard-Dose Pemetrexed Compared With Pemetrexed Monotherapy in Second-Line Treatment for Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2015 Nov;16(6):457-65. doi: 10.1016/j.cllc.2015.05.010. Epub 2015 Jun 2.