Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Pemetrexed

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

BI 6727 plus 500 mg/\^m2 pemetrexed i.v. on day 1 of 21 day cycle

500 mg/m\^2 i.v. on day 1 of a 21 day cycle

500 mg/m\^2 i.v. on day 1 of 21 day cycle

pemetrexed

BI 6727

Boehringer Ingelheim

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.

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

Disease progression was defined according to the Response Evaluation Criteria in Solid Tumours (RECIST)) criteria. Progression-free survival time was calculated as the duration from the date of randomization to the date of disease progression or death, whichever occured first. For patients with known date of progression (or death): PFS \[days\] = min (date of progression, date of death) - date of randomization + 1 day. For patients without progression or death, PFS was censored at the last imaging date that showed no disease progression: PFS \[days, censored\] = date of last imaging showing no progression - date randomization + 1 day.

The number of participants analysed displays the number of patients with an event (progression).

Objective tumor response, defined as complete response (CR), and partial response (PR), evaluated according to RECIST criteria. Evaluation of target lesions: Complete Response (CR): disappearance of all target lesions. Partial Response (PR): ≥30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Evaluation of nontarget lesions: Complete Response (CR): disappearance of all nontarget lesions.

Overall survival (OS) was defined as the duration of time from randomization to time of death.

The duration of overall response was measured from the time measurement criteria were met for CR or PR (whichever was first recorded) until the first date that recurrent or progressive disease (PD) was objectively documented (taking as reference for PD the smallest measurements recorded since treatment began). The duration of overall CR was measured from the time measurement criteria were first met for CR until the first date that recurrent disease was objectively documented. Duration of disease control is presented here.

All patients were carefully monitored during and after each treatment cycle. Adverse events (AEs) were recorded and were graded according to the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE).

Occurence of Dose-limiting toxicity (DLT). A DLT was defined as one or more of the following:

* treatment-related CTCAE Grade 3 or 4 nonhematological toxicity (except emesis or diarrhea responding to supportive treatment).
* treatment-related CTCAE Grade 4 neutropenia for ≥7 days and/or complicated by infection.
* CTCAE Grade 4 thrombocytopenia.

Frequency of patients with possible clinically significant abnormalities

Cmax - maximum measured concentration of volasertib in plasma.

CL - total clearance of volasertib in plasma after IV administration

Vss - apparent volume of distribution at steady state following IV administration of volasertib

Cmax - maximum measured concentration of pemetrexed in plasma

CL - total clearance of pemetrexed in plasma after IV administration

Vss - apparent volume of distribution at steady state following IV administration of pemetrexed

Patients received Volasertib 250 mg and pemetrexed 500 mg/m2 administered intravenously (i.v.) on day 1 of each 21 day cycle.

Run-in Phase: Volasertib 250 mg + Pemetrexed 500 mg/m2

Patients received Volasertib 300 mg and pemetrexed 500 mg/m2 administered intravenously (i.v.) on day 1 of each 21 day cycle

Run-in Phase: Volasertib 300 mg + Pemetrexed 500 mg/m2

Patients received Volasertib 300 mg administered intravenously (i.v.) on day 1 of each 21 day cycle

Randomization Phase: Volasertib 300 mg

Patients received Volasertib 300 mg and Pemetrexed 500 mg/m2 intravenously (i.v.) on day 1 of each 21 day cycle

Randomization Phase: Volasertib 300 mg + Pemetrexed 500 mg/m2

Patients received Pemetrexed 500 mg/m2 administered intravenously (i.v.) on day 1 of each 21 day cycle

Randomization Phase: Pemetrexed 500 mg/m2

Total

Age, Continuous

Sex: Female, Male

Randomized set, which included all patients randomised in the randomisation phase, whether treated or not

Boehringer Ingelheim Call Center

Hazard ratio and 95% confidence interval (CI) from Cox proportional-hazards regression model, stratified by histology (Nonsquamous vs. NOS). P-value from log-rank test stratified by histology (one-sided for volasertib 300 mg + pemetrexed 500 mg/m2 vs. pemetrexed 500 mg; two-sided for volasertib 300 mg vs. pemetrexed 500 mg/m2).

Hazard ratio and 95% CI from Cox proportional-hazards regression model, stratified by histology (Nonsquamous vs. NOS). P-value from log-rank test stratified by histology (one-sided for volasertib 300 mg + pemetrexed 500 mg/m2 vs. pemetrexed 500 mg/m2; two-sided for volasertib 300 mg vs. pemetrexed 500 mg/m2).

Randomized phase II set, which included all patients who were randomized as part of phase II of the study (not the run in phase)

Progression Free Survival (PFS) Time From the Date of Randomization to Date of Disease Progression or Death, Whichever Occurred First.

Complete response (CR)

Partial response (PR)

Objective Tumor Response, Defined as Complete Response (CR), and Partial Response (PR), Evaluated According to RECIST Criteria.

Randomized phase II set, including only patients who died.

Overall Survival (OS)

Duration of Overall Response

CTCAE Grade 1

CTCAE Grade 2

CTCAE Grade 3

CTCAE Grade 4

CTCAE Grade 5

Treated set, which included all patients who were dispensed and were documented to have taken at least one dose of investigational treatment.

Occurrence and Intensity of AEs Graded According to CTCAE.

Treated set, run-in phase, first course only

Occurence of DLT

Haemoglobin - Low

White blood cell ct. - Low

White blood cell ct. - High

Platelets - Low

Platelets - High

Neutrophils - Low

Lymphocytes - Low

AST/GOT, SGOT - High

ALT/GPT, SGPT - High

Alkaline phosphatase - High

Creatinine - High

Bilirubin, total - High

Frequency of Patients With Possible Clinically Significant Abnormalities

Volasertib 250 mg + Pemetrexed 500 mg/m2

Volasertib 300 mg + Pemetrexed 500 mg/m2

Patient received Volasertib 300 mg administered intravenously on day 1 of each 21 day cycle.

Volasertib 300 mg

Pharmacokinetic (PK) set, which included all patients in the treated set with volasertib monotherapy or combined with pemetrexed and provided at least 1 blood sample for measurement of volasertib (BI 6727) or pemetrexed. Including patients with evaluable data

Cmax of Volasertib

PK set including patients with evaluable data

Total Clearance (CL) of Volasertib

Vss of Volasertib

Cmax of Pemetrexed

CL of Pemetrexed

Vss of Pemetrexed

Patients received Volasertib 300 mg administered intravenously on day 1 of each 21 day cycle

Randomized Phase: Volasertib 300 mg

Patients received Volasertib 300 mg and Pemetrexed 500 mg/m2 intravenously on day 1 of each 21 day cycle

Spots Global Cancer Trial Database for Trial of BI 6727 (Volasertib) Monotherapy and BI 6727 in Combination With Pemetrexed Compared to Pemetrexed Monotherapy in Advanced NSCLC

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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