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

A Phase I/II Study of Continuous, Concomitant Oral Treatment With BIBF 1120 and Pemetrexed - a Phase I, Open-label, Dose-escalation Study & a Phase II, 2 Arm, Randomized, Double-blind, Placebo-controlled Study in Japanese Patients With Stage IIIB/IV or Recurrent Non-small-cell Lung Cancer After Failure of Chemotherapy

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

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: BIBF 1120 M + Pemetrexed; Drug: BIBF 1120 H + Pemetrexed; Drug: BIBF 1120 L + Pemetrexed; Drug: BIBF 1120 RD + Pemetrexed; Drug: BIBF 1120 Placebo + Pemetrexed

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba,Kashiwa, Japan
    • 1199.28.003 Boehringer Ingelheim Investigational Site
  • Miyakojima-ku, Osaka, Japan
    • 1199.28.002 Boehringer Ingelheim Investigational Site
  • Osaka-Sayama, Osaka, Japan
    • 1199.28.001 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Male or female patients of age >=20 and <=74 years at informed consent
2. Histologically or cytologically confirmed, Non Small Cell Lung Cancer (NSCLC) of stage IIIB or IV or recurrent NSCLC
3. Relapse or failure of 1 first-line prior chemotherapy
4. Life expectancy of at least 3 months
5. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1

6. 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%
7. Patient has given written informed consent which must be consistent with ICH-GCP and local legislation.

Exclusion criteria:

1. 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)
2. 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) .
3. 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)
4. Previous therapy with other vascular endothelial growth factor receptor (VEGFR) inhibitors or vascular endothelial growth factor (VEGF) ligand inhibitors for treatment of NSCLC
5. Previous therapy with BIBF 1120 and/or pemetrexed for treatment of NSCLC and any contraindications for therapy with pemetrexed
6. Patients who have active brain metastases
7. Leptomeningeal disease
8. 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).
9. Radiographic evidence of cavitary or necrotic tumors
10. Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels
11. History of clinically significant haemoptysis within the past 3 months
12. History of major thrombotic or clinically relevant major bleeding event in the past 6 months
13. Known inherited predisposition to bleeding or thrombosis
14. Significant cardiovascular diseases
15. Significant weight loss (>10%) within the past 6 weeks prior to treatment in the present trial
16. Current peripheral neuropathy CTCAE grade 2 or greater except due to trauma
17. Pre-existing ascites and/or clinically significant pleural effusion
18. Major injuries and/or surgery within the past 4 weeks prior to randomisation with incomplete wound healing
19. Clinically serious infections
20. Decompensated diabetes mellitus
21. Contraindication to high dose steroid therapy
22. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
23. Patients who have active or chronic hepatitis C and/or B infection and diagnosis of human immunodeficiency virus (HIV) infection
24. Other malignancy other than basal cell skin cancer, carcinoma in situ or intra-mucosal cancer that were judged to be cured by adequate treatment and disease-free interval is more than 5 years
25. History of serious drug hypersensitivity
26. Serious illness or concomitant non-oncological disease such as neurologic-, psychiatric-, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation
27. Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy
28. Patients who are sexually active and unwilling to use a medically acceptable method of contraception
29. Pregnancy or breast feeding
30. Active alcohol or drug abuse
31. Patients unable to comply with the protocol
32. Other patients judged ineligible for enrolment in the study by the investigator or subinvestigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIBF 1120 BID + Pemetrexed; 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; BIBF 1120 medium dose bid+ Pemetrexed 500 mg/m^2; Drug: BIBF 1120 H + Pemetrexed; BIBF 1120 high dose bid+ Pemetrexed 500 mg/m^2; Drug: BIBF 1120 L + Pemetrexed; BIBF 1120 low dose bid+ Pemetrexed 500 mg/m^2
Experimental: BIBF 1120 BID (RD) + Pemetrexed; PHase II part: Study arm	Drug: BIBF 1120 RD + Pemetrexed; confirmed dose of BIBF 1120 bid + Pemetrexed 500 mg/m^2
Experimental: BIBF 1120 BID(Placebo) + Pemetrexed; Phase II part: Comparator arm	Drug: BIBF 1120 Placebo + Pemetrexed; placebo BIBF 1120 bid + Pemetrexed 500 mg/m^2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Number of participants with complete response (CR) or partial response (PR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.0	Every 6 weeks after start of study treatment until end of treatment, up to 992 days
Disease Control Rate	Number of participants with complete response (CR), partial response (PR) or stable disease (SD) according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.0	Every 6 weeks after start of study treatment until end of treatment, up to 992 days
Duration of Disease Control	Duration of disease control was defined as the time period from the first study drug administration to the progressive disease (PD) or death of patients, whichever occurred earlier.	From first study drug administration until PD or death, up to 1003 days
Number of Participants With Clinically Relevant Abnormalities in Laboratory Parameters	Number of participants with clinically relevant abnormalities in laboratory parameters reported as adverse events which occurred in >= 20% of patients	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	Area under the concentration-time curve of nintedanib in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)	5 minutes (min) before nintedanib administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23h 55min after nintedanib administration in cycle 1
Cmax of Nintedanib	Maximum measured concentration of nintedanib in plasma (Cmax)	5 minutes (min) before nintedanib administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23h 55min after nintedanib administration in cycle 1
AUC0-inf of Pemetrexed	Area under the concentration-time curve of pemetrexed in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)	5 minutes (min) before pemetrexed administration and 10min, 40min, 1 hour (h), 2h, 4h, 6h, 23h 55min, 47h 55min after pemetrexed administration in cycles 1 and 2
Cmax of Pemetrexed	Maximum measured concentration of pemetrexed in plasma (Cmax)	5 minutes (min) before pemetrexed administration and 10min, 40min, 1 hour (h), 2h, 4h, 6h, 23h 55min, 47h 55min after pemetrexed administration in cycles 1 and 2

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2009
• Primary Completion (Actual): February 16, 2015
• Study Completion (Actual): February 16, 2015

Study Registration Dates

• First Submitted: September 17, 2009
• First Submitted That Met QC Criteria: September 17, 2009
• First Posted (Estimated): September 18, 2009

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Protein Kinase Inhibitors; Pemetrexed; Nintedanib
• Other Study ID Numbers: 1199.28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datatransparency