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

NCT00824408 | Completed Phase 2 Results

• 1 other identifier: 1230.5
• Study Type: interventional
• Target: 143
• Locations: 2 countries
• Sites: 12

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

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

  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).

  From randomization until disease progression or death

Secondary Outcomes (12)

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

  From first drug infusion until 21 days after last drug infusion, up to 1100 days

• Overall Survival (OS)

  From randomization until time of death

• Duration of Overall Response

  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

• Occurrence and Intensity of AEs Graded According to CTCAE.

  From first drug infusion until 21 days after last drug infusion, up to 1100 days

• Occurence of DLT

  Patients were treated for repeated 21-day treatment cycles until disease progression or intolerability of the trial drug, whichever occurred first.

Study Arms (2)

BI 6727 +pemetrexed

EXPERIMENTAL

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

Drug: pemetrexed; Drug: BI 6727

pemetrexed

ACTIVE COMPARATOR

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

Drug: pemetrexed

Interventions

pemetrexed DRUG

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

BI 6727 +pemetrexed

BI 6727 DRUG

BI 6727 i.v. on day 1 of a 21 day cycle

BI 6727 +pemetrexed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologic or cytologic confirmed diagnosis of NSCLC
• 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)
• Patients who are eligible for pemetrexed as second line chemotherapy
• Measurable disease by one or more techniques (CT, MRI) according to RECIST
• Patients aged 18 years or older
• Life expectancy of at least three (3) months
• Eastern Cooperative Oncology Group (ECOG) performance Score 0-2
• Written informed consent that is consistent with ICH-GCP guidelines and local legislation

You may not qualify if:

• 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
• 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
• Any persisting toxicities which are deemed to be clinically significant from the previous therapy
• 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.
• Patients who are unwilling or unable to take folic acid and vitamin B12 supplementation
• 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.
• Other active malignancy diagnosed within the past 3 years (other than non melanomatous skin cancer and cervical intraepithelial neoplasia)
• 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
• 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
• Patients who have received prior therapy with pemetrexed
• Absolute neutrophil count (ANC) less than 1,500/mm3
• Platelet count less than 100,000/mm3
• Hemoglobin \<90g/L
• Total bilirubin \>26µmol/L
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (12)

1230.5.00104 Boehringer Ingelheim Investigational Site

Edmonton, Alberta, Canada

Location

1230.5.00114 Boehringer Ingelheim Investigational Site

Kelowna, British Columbia, Canada

Location

1230.5.00109 Boehringer Ingelheim Investigational Site

Surrey, British Columbia, Canada

Location

1230.5.00107 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

Location

1230.5.00105 Boehringer Ingelheim Investigational Site

Hamilton, Ontario, Canada

Location

1230.5.00119 Boehringer Ingelheim Investigational Site

Kitchener, Ontario, Canada

Location

1230.5.00116 Boehringer Ingelheim Investigational Site

Oshawa, Ontario, Canada

Location

1230.5.00108 Boehringer Ingelheim Investigational Site

Ottawa, Ontario, Canada

Location

1230.5.00110 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1230.5.00102 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

1230.5.00106 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

1230.5.00118 Boehringer Ingelheim Investigational Site

Nassau, The Bahamas

Location

Related Publications (1)

• 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.

  PMID: 26100229 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed; BI 6727

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2009
• First Posted: January 16, 2009
• Study Start: March 1, 2009
• Primary Completion: September 1, 2012
• Study Completion: August 1, 2015
• Last Updated: September 20, 2016
• Results First Posted: September 20, 2016

Record last verified: 2016-07

Locations

CA (11); TH (1)