BIBF 1120 as Second Line Treatment for Small Cell Lung Cancer
Recruitment status was Recruiting
Small Cell Lung Cancer
Small Cell Lung Cancer Recurrent
Drug: BIBF 1120
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study Of BIBF 1120 as Second-line Treatment for Patients With Small Cell Lung Cancer|
- Overall response rate [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]To assess the efficacy of BIBF1120 as second-line treatment in patients with recurrent small cell lung caner
- Overall survival rate [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]Survival time will be calculated from the date of study treatment start to the date of death (or date last seen).
- Progression free survival [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]Progression free survival will be calculated from the date of study treatment start to the first objective documentation of progressive disease or death.
- Toxicity [ Time Frame: every 4 weeks ] [ Designated as safety issue: Yes ]Safety will be evaluated by the frequency, severity, and relationship of adverse events graded by NCI Common Toxicity Criteria (CTC) version 4.0 that occur during the treatment and follow-up periods.
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||January 2014|
|Estimated Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: study arm
BIBF 1120 study arm
Drug: BIBF 1120
BIBF 1120 200mg bid, PO, daily until PD
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01441297
|Contact: Ji-Youn Han, PhD.||+firstname.lastname@example.org|
|Contact: Sung Jin Yoon, RNemail@example.com|
|Korea, Republic of|
|National Cancer Center||Recruiting|
|Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769|
|Contact: Ji-youn Han, M.D., Ph.D. +82-31-920-1154 firstname.lastname@example.org|
|Contact: Sung Jin Yoon, RN +82-31-920-0405 email@example.com|
|Principal Investigator:||Ji-Youn Han, PhD.||National Cancer Center, Korea|