Small Cell Lung CancerPhase 2NCT01441297
BIBF 1120 as Second Line Treatment for Small Cell Lung Cancer
A Phase 2 study testing BIBF 1120 in people with Small Cell Lung Cancer and Small Cell Lung Cancer Recurrent, run by Ji-youn Han at 1 site in South Korea.
Trial summary
Although chemotherapy is the primary treatment option for small cell lung cancer (SCLC), longterm survival is rare. SCLC is initially chemosensitive, but rapidly relapses in a chemoresistant form with an overall survival of <5%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer, Small Cell Lung Cancer Recurrent
- What is being tested?
- BIBF 1120
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSouth Korea
- Study dates
- Dec 2011to 31 Mar 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed SCLC
- Progression during or after prior first line chemotherapy.
- At least one target tumor lesion RECIST 1.1)
- Life expectancy of at least three months
- ECOG PS 0-2
- Written informed consent
Who cannot join
- Previous therapy with other VGFR inhibitors (other than bevacizumab)
- Persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy
- 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
- 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
- Concomitant yellow fever vaccination
- 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
Show all 32Show fewer
- 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 (more than one teaspoon of fresh blood per day)
- 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)
- 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 (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)
- Calculated creatinine clearance by Cockcroft Gault <45ml/min
- Proteinuria CTCAE grade 2 or greater
- Total bilirubin above the upper limit of normal
- 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.
- Prothrombin time and/or partial thromboplastin time greater than 50% deviation from normal limits
- Platelets <100000 platelets/μL (=mm3)
- Significant weight loss (> 10 %) within the past 6 weeks prior to treatment in the present trial
- Current peripheral neuropathy ≥ CTCAE(version4.0) Grade 2 except due to trauma
- Pre-existing ascites and/or clinically significant pleural effusion
- Major injuries and/or surgery within the past ten days prior to randomization with incomplete wound healing
- Serious infections requiring systemic antibiotic (e.g. antiviral, antimicrobial, antifungal) therapy
- Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
- Active or chronic hepatitis C and/or B infection
- Known human immunodeficiency virus (HIV) seropositivity
- serious illness or concomitant non-oncological disease or
- Pregnancy or breast feeding
- Active alcohol or drug abuse
- Other malignancy within the past three years
- Hypersensitivity to BIBF 1120 and/or the excipients of the trial drugs
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study Of BIBF 1120 as Second-line Treatment for Patients With Small Cell Lung Cancer
Although chemotherapy is the primary treatment option for small cell lung cancer (SCLC), longterm survival is rare. SCLC is initially chemosensitive, but rapidly relapses in a chemoresistant form with an overall survival of <5%. Consequently, novel therapies are urgently required and will likely arise from an improved understanding of the disease biology. Some preclinical studies have showed that fibroblast growth factor-2 induces proliferation and
Read the detailed description
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.
- Being tested
- BIBF 1120
- Keywords
- recurrent small cell lung cancer
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIBF 1120Drug
BIBF 1120 200mg bid, PO, daily until PD
| Study group | Role | What they receive |
|---|---|---|
| study arm | Experimental | BIBF 1120 study arm Receives: Drug: BIBF 1120 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
To assess the efficacy of BIBF1120 as second-line treatment in patients with recurrent small cell lung caner
Measured: every 8 weeks
Secondary outcomes (3)
Overall survival rate
Survival time will be calculated from the date of study treatment start to the date of death (or date last seen).
Measured: every 8 weeks
Progression free survival
Progression free survival will be calculated from the date of study treatment start to the first objective documentation of progressive disease or death.
Measured: every 8 weeks
Toxicity
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.
Measured: every 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2011 (estimated)
- Study startDec 2011
- Primary completion31 Oct 2015
- Study completion31 Mar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ji-youn Han
- Sponsor type
- Other government
- Collaborators
- National Cancer Center, Korea
- Responsible party
- Sponsor-investigator, Ji-youn Han, National Cancer Center, Korea
- Investigators
- Ji-Youn Han, PhD., Principal investigator, National Cancer Center, Korea
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01441297
- Sponsor's protocol ID
- NCCCTS-10-525
- Status last verified
- Aug 2017
- First submitted
- 23 Sep 2011
- Last updated
- 25 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Han JY, Kim HY, Lim KY, Hwangbo B, Lee JS. A phase II study of nintedanib in patients with relapsed small cell lung cancer. Lung Cancer. 2016 Jun;96:108-12. doi: 10.1016/j.lungcan.2016.04.002. Epub 2016 Apr 6.
PubMed 27133759
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study Of BIBF 1120 as Second-line Treatment for Patients With Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT01441297
- Acronym / sponsor ID
- NCCCTS-10-525
- Keywords
- recurrent small cell lung cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Ji-youn HanOther government
- Collaborators
- National Cancer Center, Korea
- Study start
- Dec 2011 (actual)
- Primary completion
- 31 Oct 2015 (actual)
- Study completion
- 31 Mar 2016 (actual)
- First posted
- 27 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Although chemotherapy is the primary treatment option for small cell lung cancer (SCLC), longterm survival is rare. SCLC is initially chemosensitive, but rapidly relapses in a chemoresistant form with an overall survival of <5%. Consequently, novel therapies are urgently required and will likely arise from an improved understanding of the disease biology. Some preclinical studies have showed that fibroblast growth factor-2 induces proliferation and
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| study arm | Experimental | Drug: BIBF 1120BIBF 1120 study arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically confirmed SCLC
- Progression during or after prior first line chemotherapy.
- At least one target tumor lesion RECIST 1.1)
- Life expectancy of at least three months
- ECOG PS 0-2
Key exclusion criteria (32 listed)
- Previous therapy with other VGFR inhibitors (other than bevacizumab)
- Persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy
- 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
- 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
- Concomitant yellow fever vaccination
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BIBF 1120BIBF 1120 200mg bid, PO, daily until PD | Drug | study arm |
Primary outcome
Overall response rate
Time frame: every 8 weeks
To assess the efficacy of BIBF1120 as second-line treatment in patients with recurrent small cell lung caner
3 secondary outcomes
Overall survival rate
Time frame: every 8 weeks
Progression free survival
Time frame: every 8 weeks
Toxicity
Time frame: every 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2017.
- Derived from this study: PubMed 27133759Han JY, Kim HY, Lim KY, Hwangbo B, Lee JS. A phase II study of nintedanib in patients with relapsed small cell lung cancer. Lung Cancer. 2016 Jun;96:108-12. doi: 10.1016/j.lungcan.2016.04.002. Epub 2016 Apr 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ji-Youn Han, PhD. principal investigator
National Cancer Center, Korea
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BIBF 1120 in people with Small Cell Lung Cancer and Small Cell Lung Cancer Recurrent, run by Ji-youn Han at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (time frame: every 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01441297, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2017.