Recurrent Non-small Cell Lung CancerPhase 2NCT01948141
Nintedanib in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed Up to Two Previous Chemotherapy Regimens
A Phase 2 study testing nintedanib in people with Recurrent Non-small Cell Lung Cancer and Squamous Cell Lung Cancer, run by Roswell Park Cancer Institute at 2 sites in United States.
Trial summary
This phase II trial studies how well nintedanib works in treating patients with advanced non-small cell lung cancer who have failed up to two previous chemotherapy regimens. Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Non-small Cell Lung Cancer, Squamous Cell Lung Cancer, Stage III Non-small Cell Lung Cancer
- What is being tested?
- nintedanib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesUnited States
- Study dates
- 30 Jan 2014to 16 Aug 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients with advanced histologically proven squamous cell carcinoma of the lung
- Patients who have failed at least 1 systemic chemotherapy regimen for metastatic disease, but not more than 2 regimens
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
- The pathologic tissue is available to determine FGFR1 amplification status
- Presence of either evaluable disease or measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Absolute neutrophil count (ANC) >= 1500/uL
Show all 14Show fewer
- Hemoglobin (HgB) >= 9 g/dL
- Platelets >= 100,000/uL
- Total bilirubin =< upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 1.5 x ULN (ALT and AST =< 2.5 x ULN is acceptable if there is liver metastasis)
- Calculated or measured creatinine clearance >= 45 mL/min
- Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment and have a negative serum or urine pregnancy test done =< 7 days prior to registration (for women of childbearing potential only)
- Life expectancy >= 12 weeks
- Willingness to provide the blood specimens as required by the protocol; please note that the willingness to participate pertains only to the patient and does not factor in the institution's ability to participate in any part of the translational component
Who cannot join
- Patients with any known endothelial growth factor receptor (EGFR) mutation and/or anaplastic lymphoma receptor tyrosine kinase (ALK) translocation
- Symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases or seizure disorder; patients with asymptomatic CNS metastases treated with whole brain radiation (WBRT) or gamma knife radiosurgery (GKR) may be enrolled >= 1 week after completion of WBRT/GKR provided toxicities are =< Common Toxicity Criteria (CTC) grade I at the time of registration and/or controlled with dexamethasone 2 mg once daily for at least 5 days at the time of study treatment; patients with symptomatic CNS metastases treated with WBRT/GKR may be enrolled >= 2 weeks after completion of WBRT/GKR provided toxicities are =< CTC grade 1 at the time of registration and neurologic symptoms controlled with dexamethasone =< 2 mg once daily for at least 1 week at the time of study treatment
- Patients receiving palliative radiation to skeletal metastases may be registered as early as 1 week after completion of radiation therapy provided toxicities are =< CTC grade I at the time of registration
- Any of the following prior therapies for malignancy:
- Systemic chemotherapy =< 4 weeks prior to registration
- Radiation therapy =< 4 weeks prior to registration (exceptions noted in the prior bullet); the site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease
Show all 34Show fewer
- Major surgery (i.e., laparotomy), open biopsy, or significant traumatic injury =< 4 weeks prior to registration; minor surgery =< 2 weeks prior to registration; insertion of a vascular access device is not considered major or minor surgery in this regard
- Other investigational agent =< 30 days prior to study treatment
- The following patients will be excluded from this study:
- Pregnant women
- Breastfeeding women
- Men or women who are sexually active and unwilling to use a medically acceptable method of contraception (e.g., such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial and for at least three months after end of active therapy; a highly effective method of birth control is defined as one which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly; patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least 2 years
- Second primary malignancy with the following exceptions which are allowed:
- Carcinoma in situ of the cervix
- Non-melanoma skin cancer
- History of low-grade (Gleason score =< 6) localized prostate cancer even if diagnosed < 5 years prior to registration
- Treated stage I breast cancer even if diagnosed =< 5 years prior to registration
- Other prior malignancy (including melanoma) allowed if it was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of BIBF 1120 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or extensive small bowel resection)
- Leptomeningeal disease
- Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded because of possible pharmacokinetic interactions with oral investigational agents
- Unwilling to, or unable to, comply with the protocol
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring systemic antimicrobial therapy (including history of active or chronic hepatitis C and/or hepatitis B infection), significant pulmonary symptoms at baseline due to disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Centrally located tumors with radiographic evidence (computed tomography [CT] or magnetic resonance imaging [MRI]) of local invasion of major blood vessels
- Significant weight loss (> 10% of baseline body mass) within past 6 months prior to inclusion into the study
- Coagulation parameters: International normalized ratio (INR) > 2, prothrombin time (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN
- Proteinuria by Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater
- Known inherited predisposition to bleeding or thrombosis
- Therapeutic anticoagulation (except for low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous device) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325 mg per day)
- Baseline hemoptysis, per clinician/investigator evaluation
- Active alcohol or drug abuse
- History of arterial or venous thrombotic/embolic events =< 12 months prior to registration
- Prior history with BIBF 1120 or any other vascular endothelial growth factor (VEGF)/VEGF receptor (R) inhibitor
- New York Heart Association (NYHA) class III or IV; NOTE: patients classified as NYHA class II controlled with treatment may participate, with increased monitoring
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
University Hospitals Case Medical Center
Cleveland, Ohio, 44106
About this study
Official title: FGFR1 Amplification as A Predictor of Efficacy in A Biomarker-Driven Phase II Study of BIBF 1120 in Advanced Squamous Cell Lung Cancer Patients Who Have Failed Up to Two Prior Chemotherapeutic Regimens
This phase II trial studies how well nintedanib works in treating patients with advanced non-small cell lung cancer who have failed up to two previous chemotherapy regimens. Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the 6-month progression-free survival (PFS) rate of fibroblast growth factor receptor 1 (FGFR1) amplified squamous cell lung cancer patients treated with BIBF 1120 (nintedanib).
SECONDARY OBJECTIVES:
- Compare the 6-month PFS rate for the entire FGFR1 amplified group versus the FGFR1 non-amplified patients.
II. Compare the 6-month PFS rate for each FGFR1 amplified group (low, intermediate, and high) versus historical controls and FGFR1 non-amplified patients.
III. To assess the following endpoints overall and by FGFR1 group: PFS, overall survival (OS), confirmed tumor response rate, and adverse events.
TERTIARY OBJECTIVES:
- The relation of FGFR1 gene copy number with PFS, OS, confirmed response rate, and adverse events.
II. The relationship fibroblast growth factor receptor (FGFR) polymorphisms with toxicity and efficacy.
OUTLINE:
Patients receive nintedanib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 8 weeks.
- Conditions
- Recurrent Non-small Cell Lung Cancer, Squamous Cell Lung Cancer, Stage III Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
- Being tested
- nintedanib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nintedanibDrug
Also called BIBF 1120, multitargeted tyrosine kinase inhibitor BIBF 1120, Tyrosine Kinase Inhibitor BIBF 1120, Vargatef
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (nintedanib) | Experimental | Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: nintedanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-month Progression Free Survival (PFS) Rate Within the Entire FGFR1 Amplified Group
The 6-month PFS rate was defined as the proportion of patients who were alive and progression-free at 6 months after start of study treatment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Measured: At 6 months
Secondary outcomes (7)
Compare the 6-month PFS Rate for the Entire FGFR1 Amplified Group Versus the FGFR1 Non-amplified Patients.
The 6-month PFS rate was defined as the proportion of patients who were alive and progression-free at 6 months after start of study treatment.
Measured: Time from study entry to the first of either disease progression or death, assessed at 6 months
Compare the 6-month PFS Rate for Each FGFR1 Amplified Group (Low, Intermediate, and High) Versus FGFR1 Non-amplified Patients.
The 6-month PFS rate was defined as the proportion of patients who were alive and progression-free at 6 months after start of study treatment.
Measured: Time from study entry to the first of either disease progression or death, assessed at 6 months
6-month PFS Rate for Each of the FGFRI Amplified Groups (Low, Intermediate, High) in Comparison to Historical Controls
The 6-month PFS rate was defined as the proportion of patients who were alive and progression-free at 6 months after start of study treatment.
Measured: Time from study entry to the first of either disease progression or death, assessed at 6 months
Overall Survival (OS)
Overall survival (OS) was defined as the time from study entry to death from any cause.
Measured: From study entry to death from any cause, assessed up to 3 years
Tumor Response Rate
Tumor Response rate was defined as the proportion of patients who had Complete Response (CR) or Partial Response (PR) by RECIST 1.1 Criteria. Complete Response (CR): Disappearance of all target lesions. Any lymph nodes must have a reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Up to 3 years
Incidence of Adverse Events (AEs)
Percentage of participants with adverse events. Incidence of Adverse Events (AEs) was Accessed by the National Cancer Institute (NCI) CTCAE Version 4.0.
Measured: Up to 30 days post-treatment
Progression Free Survival
Progression-free survival (PFS) was defined as the time from study entry to the first of either disease progression or death.
Measured: Time from study entry to the first of either disease progression or death, assessed up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2013 (estimated)
- Study start30 Jan 2014
- Primary completion16 Aug 2016
- Study completion16 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Roswell Park Cancer InstituteThe sponsor's other registered studies.
- 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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Boehringer Ingelheim
- Responsible party
- Sponsor
- Investigators
- Hongbin Chen, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01948141
- Sponsor's protocol ID
- I 225512
- Other IDs
- NCI-2013-01618, I 225512, P30CA016056
- Status last verified
- May 2017
- First submitted
- 18 Sep 2013
- Last updated
- 8 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FGFR1 Amplification as A Predictor of Efficacy in A Biomarker-Driven Phase II Study of BIBF 1120 in Advanced Squamous Cell Lung Cancer Patients Who Have Failed Up to Two Prior Chemotherapeutic Regimens
- ClinicalTrials.gov ID
- NCT01948141
- Acronym / sponsor ID
- I 225512
- Conditions
- Recurrent Non-small Cell Lung Cancer, Squamous Cell Lung Cancer, Stage III Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Boehringer Ingelheim
- Study start
- 30 Jan 2014 (actual)
- Primary completion
- 16 Aug 2016 (actual)
- Study completion
- 16 Aug 2016 (actual)
- First posted
- 23 Sep 2013 (estimated)
- Results
- Posted 8 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well nintedanib works in treating patients with advanced non-small cell lung cancer who have failed up to two previous chemotherapy regimens. Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the 6-month progression-free survival (PFS) rate of fibroblast growth factor receptor 1 (FGFR1) amplified squamous cell lung cancer patients treated with BIBF 1120 (nintedanib).
SECONDARY OBJECTIVES:
- Compare the 6-month PFS rate for the entire FGFR1 amplified group versus the FGFR1 non-amplified patients.
II. Compare the 6-month PFS rate for each FGFR1 amplified group (low, intermediate, and high) versus historical controls and FGFR1 non-amplified patients.
III. To assess the following endpoints overall and by FGFR1 group: PFS, overall survival (OS), confirmed tumor response rate, and adverse events.
TERTIARY OBJECTIVES:
- The relation of FGFR1 gene copy number with PFS, OS, confirmed response rate, and adverse events.
II. The relationship fibroblast growth factor receptor (FGFR) polymorphisms with toxicity and efficacy.
OUTLINE:
Patients receive nintedanib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 8 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (nintedanib) | Experimental | Drug: nintedanibPatients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients with advanced histologically proven squamous cell carcinoma of the lung
- Patients who have failed at least 1 systemic chemotherapy regimen for metastatic disease, but not more than 2 regimens
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
- The pathologic tissue is available to determine FGFR1 amplification status
- Presence of either evaluable disease or measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Key exclusion criteria (34 listed)
- Patients with any known endothelial growth factor receptor (EGFR) mutation and/or anaplastic lymphoma receptor tyrosine kinase (ALK) translocation
- Symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases or seizure disorder; patients with asymptomatic CNS metastases treated with whole brain radiation (WBRT) or gamma knife radiosurgery (GKR) may be enrolled >= 1 week after completion of WBRT/GKR provided toxicities are =< Common Toxicity Criteria (CTC) grade I at the time of registration and/or controlled with dexamethasone 2 mg once daily for at least 5 days at the time of study treatment; patients with symptomatic CNS metastases treated with WBRT/GKR may be enrolled >= 2 weeks after completion of WBRT/GKR provided toxicities are =< CTC grade 1 at the time of registration and neurologic symptoms controlled with dexamethasone =< 2 mg once daily for at least 1 week at the time of study treatment
- Patients receiving palliative radiation to skeletal metastases may be registered as early as 1 week after completion of radiation therapy provided toxicities are =< CTC grade I at the time of registration
- Any of the following prior therapies for malignancy:
- The following patients will be excluded from this study:
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 |
|---|---|---|
| nintedanibAlso: BIBF 1120, multitargeted tyrosine kinase inhibitor BIBF 1120, Tyrosine Kinase Inhibitor BIBF 1120, VargatefGiven PO | Drug | Treatment (nintedanib) |
Primary outcome
6-month Progression Free Survival (PFS) Rate Within the Entire FGFR1 Amplified Group
Time frame: At 6 months
The 6-month PFS rate was defined as the proportion of patients who were alive and progression-free at 6 months after start of study treatment. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
7 secondary outcomes
Compare the 6-month PFS Rate for the Entire FGFR1 Amplified Group Versus the FGFR1 Non-amplified Patients.
Time frame: Time from study entry to the first of either disease progression or death, assessed at 6 months
Compare the 6-month PFS Rate for Each FGFR1 Amplified Group (Low, Intermediate, and High) Versus FGFR1 Non-amplified Patients.
Time frame: Time from study entry to the first of either disease progression or death, assessed at 6 months
6-month PFS Rate for Each of the FGFRI Amplified Groups (Low, Intermediate, High) in Comparison to Historical Controls
Time frame: Time from study entry to the first of either disease progression or death, assessed at 6 months
Overall Survival (OS)
Time frame: From study entry to death from any cause, assessed up to 3 years
Tumor Response Rate
Time frame: Up to 3 years
Incidence of Adverse Events (AEs)
Time frame: Up to 30 days post-treatment
Progression Free Survival
Time frame: Time from study entry to the first of either disease progression or death, assessed up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Recurrent Non-small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingObservational study
Patient-Specific MRD Liquid Biopsy in Resected NSCLC: Plasma and Bronchial Washing ctDNA
Non-Small Cell Lung Cancer, Minimal Residual Disease
RecruitingPhase 3
Testing the Impact of an Anti-Cancer Drug, Atezolizumab, After Surgery to Prevent Early Stage Non-small Cell Lung Cancer From Returning, AASI-NSCLC Trial
Lung Non-Small Cell Carcinoma
RecruitingPhase 3
Osimertinib With or Without Bevacizumab as Initial Treatment for Patients With EGFR-Mutant Lung Cancer
Advanced Lung Non-Squamous Non-Small Cell Carcinoma, Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
RecruitingPhase 1
A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors
Metastatic Solid Tumor, Recurrent Solid Tumor
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.
Hongbin Chen principal investigator
Roswell Park Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing nintedanib in people with Recurrent Non-small Cell Lung Cancer and Squamous Cell Lung Cancer, run by Roswell Park Cancer Institute at 2 sites in United States.
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 14 inclusion and 34 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 8 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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?
Yes. Results are posted in the registry (first posted 8 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
6-month Progression Free Survival (PFS) Rate Within the Entire FGFR1 Amplified Group (time frame: At 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Jun 2017.