BIBF 1120 in Combination With Pemetrexed in Advanced Non Small Cell Lung Cancer (NSCLC)

NCT00979576 | Terminated Phase 1 Results

• 1 other identifier: 1199.28
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

Brief Summary

The objectives of this trial are to estimate the following in Japanese patients with advanced NSCLC of stage IIIB/IV or with recurrence after failure of first-line chemotherapy. Phase I part The objective of the phase I part is to define the Maximum Tolerated Dose (MTD) of BIBF 1120 at a dose level up to twice daily 200 mg with standard dose of pemetrexed (500 mg/m\^2) and to determine the Recommended Dose (RD) for the phase II part. Phase II, to investigate the efficacy and safety of BIBF 1120 in combination with pemetrexed (500 mg/m\^2) as compared to pemetrexed (500 mg/m\^2) + placebo

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities

  Number of participants with dose limiting toxicity (DLT) in combination therapy of BIBF 1120 and pemetrexed during the first course

  During the first course, 21 days

• Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses

  Number of patients with adverse events according to worst Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 for all courses. CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE) or 5 (death related to AE).

  Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days

Secondary Outcomes (8)

• Overall Response Rate

  Every 6 weeks after start of study treatment until end of treatment, up to 992 days

• Disease Control Rate

  Every 6 weeks after start of study treatment until end of treatment, up to 992 days

• Duration of Disease Control

  From first study drug administration until PD or death, up to 1003 days

• Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters

  Between first administration of pemetrexed and 28 days after last administration of pemetrexed and/or BIBF 1120, up to 1020 days

• AUC0-inf of Nintedanib

  5 minutes (min) before nintedanib administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23h 55min after nintedanib administration in cycle 1

Study Arms (3)

BIBF 1120 BID + Pemetrexed

EXPERIMENTAL

Phase I part: Find MTD by using low, medium or high BIBF 1120 twice daily and 500mg/m\^2 pemetrexed once every 3 weeks

Drug: BIBF 1120 M + Pemetrexed; Drug: BIBF 1120 H + Pemetrexed; Drug: BIBF 1120 L + Pemetrexed

BIBF 1120 BID (RD) + Pemetrexed

EXPERIMENTAL

PHase II part: Study arm

Drug: BIBF 1120 RD + Pemetrexed

BIBF 1120 BID(Placebo) + Pemetrexed

EXPERIMENTAL

Phase II part: Comparator arm

Drug: BIBF 1120 Placebo + Pemetrexed

Interventions

BIBF 1120 M + Pemetrexed DRUG

BIBF 1120 medium dose bid+ Pemetrexed 500 mg/m\^2

BIBF 1120 BID + Pemetrexed

BIBF 1120 H + Pemetrexed DRUG

BIBF 1120 high dose bid+ Pemetrexed 500 mg/m\^2

BIBF 1120 BID + Pemetrexed

BIBF 1120 RD + Pemetrexed DRUG

confirmed dose of BIBF 1120 bid + Pemetrexed 500 mg/m\^2

BIBF 1120 BID (RD) + Pemetrexed

BIBF 1120 L + Pemetrexed DRUG

BIBF 1120 low dose bid+ Pemetrexed 500 mg/m\^2

BIBF 1120 BID + Pemetrexed

BIBF 1120 Placebo + Pemetrexed DRUG

placebo BIBF 1120 bid + Pemetrexed 500 mg/m\^2

BIBF 1120 BID(Placebo) + Pemetrexed

Eligibility Criteria

• Age: 20 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients of age \>=20 and \<=74 years at informed consent
• Histologically or cytologically confirmed, Non Small Cell Lung Cancer (NSCLC) of stage IIIB or IV or recurrent NSCLC
• Relapse or failure of 1 first-line prior chemotherapy
• Life expectancy of at least 3 months
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
• Patients who have sufficient baseline organ function over 4 weeks and whose laboratory data meet the following criteria at the enrolment
• Haemoglobin \>=9.0 g/dL
• Absolute neutrophil count (ANC) \>=1500/mm\^3
• Platelet count \>=100 000/mm\^3
• Total bilirubin under the upper limit of normal
• AST/SGOT and/or ALT/GPT \<=1.5 x upper limit of normal (if related to liver metastases \<=2.5 x upper limit of normal also)
• Proteinuria Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less
• Calculated creatinine clearance by Cockcroft Gault \>=45 mL/min
• Prothrombin time-international normalized ratio (PT-INR) and/or partial thromboplastin time (PTT) greater than 50% deviation from normal limits
• arterial oxgen pressure (PaO2) \>=60 torr or oxygen saturation by pulse-oximeter SpO2 \>=92%

You may not qualify if:

• Patients who have received treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with this trial or who have not recovered from side effects of such therapy (except for alopecia)
• Patients who have received chemo-, hormone-, immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug or who have not recovered from side effects of such therapy (except for alopecia) .
• Patients who have received radiotherapy within the following period Phase I part: the past 4 weeks prior to treatment with the trial drug (in case of palliative radiotherapy such as for extremities, within the past 2 weeks prior to treatment with the trial drug)
• Previous therapy with other vascular endothelial growth factor receptor (VEGFR) inhibitors or vascular endothelial growth factor (VEGF) ligand inhibitors for treatment of NSCLC
• Previous therapy with BIBF 1120 and/or pemetrexed for treatment of NSCLC and any contraindications for therapy with pemetrexed
• Patients who have active brain metastases
• Leptomeningeal disease
• Patients with distinct or suspected pulmonary fibrosis or interstitial lung disease by the CT findings, or patients with a previous history of pulmonary fibrosis or interstitial lung disease (except irradiation-pneumonitis appearing radiation field with past radiotherapy).
• Radiographic evidence of cavitary or necrotic tumors
• Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels
• History of clinically significant haemoptysis within the past 3 months
• History of major thrombotic or clinically relevant major bleeding event in the past 6 months
• Known inherited predisposition to bleeding or thrombosis
• Significant cardiovascular diseases
• Significant weight loss (\>10%) within the past 6 weeks prior to treatment in the present trial

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (3)

1199.28.003 Boehringer Ingelheim Investigational Site

Chiba,Kashiwa, Japan

Location

1199.28.002 Boehringer Ingelheim Investigational Site

Miyakojima-ku, Osaka, Japan

Location

1199.28.001 Boehringer Ingelheim Investigational Site

Osaka-Sayama, Osaka, Japan

Location

Related Publications (1)

• Daga H, Takeda K, Okada H, Miyazaki M, Ueda S, Kaneda H, Okamoto I, Yoh K, Goto K, Konishi K, Sarashina A, Tanaka T, Kaiser R, Nakagawa K. Phase I study of nintedanib in combination with pemetrexed as second-line treatment of Japanese patients with advanced non-small cell lung cancer. Cancer Chemother Pharmacol. 2015 Dec;76(6):1225-33. doi: 10.1007/s00280-015-2896-3. Epub 2015 Nov 11.

  PMID: 26560486 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed

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

Limitations and Caveats

The trial was planned to comprise of two parts, with the phase II being based on the results of another study. The other study was stopped early due to futility analysis therefore only phase I of the study was completed.

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 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2009
• First Posted: September 18, 2009
• Study Start: October 16, 2009
• Primary Completion: February 16, 2015
• Study Completion: February 16, 2015
• Last Updated: March 6, 2025
• Results First Posted: November 20, 2014

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

JP (3)