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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00979576
First received: September 17, 2009
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

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/m2) 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/m2) as compared to pemetrexed (500 mg/m2) + placebo


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: BIBF 1120 M + Pemetrexed
Drug: BIBF 1120 H + Pemetrexed
Drug: BIBF 1120 RD + Pemetrexed
Drug: BIBF 1120 L + Pemetrexed
Drug: BIBF 1120 Placebo + Pemetrexed
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Phase I part: Maximum Tolerated Dose (MTD) in combination therapy of BIBF 1120 and pemetrexed (500 mg/m2) and Adverse Events (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Phase II part: Progression Free Survival (PFS) [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase I part: Pharmacokinetic (PK), Tumor response and Safety laboratory parameters [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Phase II part: Tumor response, Overall Survival (OS), Clinical improvement, AE according to CTCAE, Safety laboratory parameters, Quality of Life (QOL) and PK [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: October 2009
Estimated Study Completion Date: May 2014
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBF 1120 BID + Pemetrexed
Phase I part: Find MTD by using low, medium or high BIBF 1120 twice daily and 500mg/m2 pemetrexed once every 3 weeks
Drug: BIBF 1120 M + Pemetrexed
BIBF 1120 medium dose bid+ Pemetrexed 500 mg/m2
Drug: BIBF 1120 H + Pemetrexed
BIBF 1120 high dose bid+ Pemetrexed 500 mg/m2
Drug: BIBF 1120 L + Pemetrexed
BIBF 1120 low dose bid+ Pemetrexed 500 mg/m2
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/m2
Experimental: BIBF 1120 BID(Placebo) + Pemetrexed
Phase II part: Comparator arm
Drug: BIBF 1120 Placebo + Pemetrexed
placebo BIBF 1120 bid + Pemetrexed 500 mg/m2

  Eligibility

Ages Eligible for Study:   20 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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/mm3
    • Platelet count >=100 000/mm3
    • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00979576

Locations
Japan
1199.28.003 Boehringer Ingelheim Investigational Site
Chiba,Kashiwa, Japan
1199.28.002 Boehringer Ingelheim Investigational Site
Miyakojima-ku, Osaka, Japan
1199.28.001 Boehringer Ingelheim Investigational Site
Osaka-Sayama, Osaka, Japan
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00979576     History of Changes
Other Study ID Numbers: 1199.28
Study First Received: September 17, 2009
Last Updated: April 2, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on April 15, 2014