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A Phase II Study Of BIBF 1120 as Second-line Treatment for Patients With Small Cell Lung Cancer

Phase 2
18 Years
Open (Enrolling)
Small Cell Lung Cancer, Small Cell Lung Cancer Recurrent

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Trial Information

A Phase II Study Of BIBF 1120 as Second-line Treatment for Patients With Small Cell Lung Cancer

Chemotherapy is the primary treatment option for patients with small cell lung cancer
(SCLC), leading to a 5-year survival of about 20% in limited disease (LD), and less than 5%
in extensive disease (ED). Although initial tumor response rate to chemotherapy is very high
(up to 96% for LD and up to 65% in ED), SCLC relapses in approximately 4 months in ED and 12
months in LD. Despite the administration of second-line chemotherapy, the overall median
survival of patients with limited and extensive disease is approximately 18 and 9 months,
respectively. In the setting of second-line therapy, response rates to chemotherapy range
between 15 and 25%, with median survival in the range of 4-6 months. Second-line therapeutic
options include cyclophosphamide, doxorubicin and vincristine (CAV) given every 3 weeks or
topotecan, which have similar response rates, time to progression and survival in the two
treatment arms (topotecan 24%, 13 and 24.7 weeks; CAV 18%, 12 and 22 weeks, respectively).
However, both treatments have substantial toxicities, with 9% of patients on trial
withdrawing for toxicity reasons. Treatment-associated mortality was as high as 4.7%
(possibly and definitely related), and many patients required transfusion support. Thus,
while these treatments have acceptable activity second-line, more active and less toxic
treatments are required for this patient population.

The next generation of anti-angiogenic drugs aims to improve clinical efficacy by targeting
multiple angiogenic factors. This approach was validated by a recent analysis of BIBF 1120,
which inhibits vascular endothelial growth factor receptors (VEGFRs), platelet-derived
growth factor receptors (PDGFRs) and the fibroblast growth factor receptors (FGFRs). BIBF
1120 resulted in growth inhibition of tumours in syngeneic rats and human tumour xenografts
in nude mice. It also displayed a favourable cellular duration of action and pharmacodynamic
profile and was well-tolerated. These data complement early-phase clinical data suggesting
that BIBF 1120 might be an effective anti-angiogenic agent. Some preclinical studies have
showed that fibroblast growth factor-2 induces proliferation and chemoresistance in SCLC
cells. In addition, the selective fibroblast growth factor receptor (FGFR) inhibitor
PD173074 blocks H-510 and H-69 SCLC proliferation and clonogenic growth in a dose-dependent
fashion and prevents FGF-2-induced chemoresistance. BIBF1120 is a novel, orally available,
potent triple angiokinase inhibitor that predominantly blocks the FGFR in addition to
vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor
(PDGFR). Therefore, the investigators will conduct a phase II trial to evaluate the efficacy
of BIBF1120 in patients with recurrent SCLC.

Inclusion Criteria:

1. Histologically confirmed SCLC

2. Progression during or after prior first line chemotherapy.

3. At least one target tumor lesion RECIST 1.1)

4. Life expectancy of at least three months

5. ECOG PS 0-2

6. Written informed consent

Exclusion Criteria:

1. Previous therapy with other VGFR inhibitors (other than bevacizumab)

2. Persistence of clinically relevant therapy related toxicities from previous
chemotherapy and/or radiotherapy

3. Chemo-, hormone-, immunotherapy with monoclonal antibodies, treatment with tyrosine
kinase inhibitors, or radiotherapy (except for brain and extremities) within the past
3 weeks prior to treatment with the trial drug i.e., the minimum time elapsed since
the last anticancer therapy and the first administration of BIBF 1120 must be 3 weeks

4. Treatment with other investigational drugs or treatment in another clinical trial
within the past three weeks before start of therapy or concomitantly with this trial

5. Concomitant yellow fever vaccination

6. Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or
leptomeningeal disease. Patients should have completed surgery or radiation therapy
for existing brain metastases, should not have documented increase in size over the
previous 3 months and should be asymptomatic off steroids

7. Radiographic evidence of cavitary or necrotic tumors

8. Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of
major blood vessels

9. History of clinically significant haemoptysis within the past 3 months (more than one
teaspoon of fresh blood per day)

10. Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed
for maintenance of an indwelling intravenous device) or antiplatelet therapy (except
for chronic low-dose therapy with acetylsalicylic acid ≤325mg per day)

11. History of major thrombotic or clinically relevant major bleeding event in the past 6

12. Known inherited predisposition to bleeding or thrombosis

13. Significant cardiovascular diseases (i.e., hypertension not controlled by medical
therapy, unstable angina, history of myocardial infarction within the past 12 months,
congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion)

14. Calculated creatinine clearance by Cockcroft Gault <45ml/min

15. Proteinuria CTCAE grade 2 or greater

16. Total bilirubin above the upper limit of normal

17. ALT and/or AST > 2.5 x upper limit of normal in the presence of live metastasis or
ALT and/or AST >1.5 x upper limit of normal in patients without liver metastasis.

18. Prothrombin time and/or partial thromboplastin time greater than 50% deviation from
normal limits

19. Platelets <100000 platelets/μL (=mm3)

20. Significant weight loss (> 10 %) within the past 6 weeks prior to treatment in the
present trial

21. Current peripheral neuropathy ≥ CTCAE(version4.0) Grade 2 except due to trauma

22. Pre-existing ascites and/or clinically significant pleural effusion

23. Major injuries and/or surgery within the past ten days prior to randomization with
incomplete wound healing

24. Serious infections requiring systemic antibiotic (e.g. antiviral, antimicrobial,
antifungal) therapy

25. Gastrointestinal disorders or abnormalities that would interfere with absorption of
the study drug

26. Active or chronic hepatitis C and/or B infection

27. Known human immunodeficiency virus (HIV) seropositivity

28. serious illness or concomitant non-oncological disease or

29. Pregnancy or breast feeding

30. Active alcohol or drug abuse

31. Other malignancy within the past three years

32. Hypersensitivity to BIBF 1120 and/or the excipients of the trial drugs

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall response rate

Outcome Description:

To assess the efficacy of BIBF1120 as second-line treatment in patients with recurrent small cell lung caner

Outcome Time Frame:

every 8 weeks

Safety Issue:


Principal Investigator

Ji-Youn Han, PhD.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Center, Korea


South Korea: Korea Food and Drug Administration (KFDA)

Study ID:




Start Date:

December 2011

Completion Date:

January 2014

Related Keywords:

  • Small Cell Lung Cancer
  • Small Cell Lung Cancer Recurrent
  • recurrent small cell lung cancer
  • Lung Neoplasms
  • Small Cell Lung Carcinoma