Carcinoma, Non-Small-Cell LungPhase 2NCT02299141
Nintedanib in Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer
A Phase 2 study testing Nintedanib in people with Carcinoma, Non-Small-Cell Lung and Non-Small Cell Lung Cancer, run by Washington University School of Medicine at 1 site in United States.
Trial summary
There has been limited benefit with angiogenesis inhibitor drugs in molecularly unselected patients in non-small cell lung cancer (NSCLC). The investigators propose that patients who are molecularly selected for treatment with nintedanib based on the presence of mutations in the following genes: VEGFR1-3, PDGFR-A… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung, Non-Small Cell Lung Cancer, Nonsmall Cell Lung Cancer
- What is being tested?
- Nintedanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 7 May 2015to 23 Apr 2025
- 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
- Histologically confirmed diagnosis of advanced (metastatic or unresectable) NSCLC with mutations, rearrangement and fusion involving RET oncogene, or abnormalities (non-synonymous SNV or amplification) in the nintedanib target genes VEGFR1-3, TP53, PDGFR-A, PDGFR-B, and FGFR1-3. CLIA certified lab testing for nintedanib target genes using cell free DNA from peripheral blood and/or assays performed on tumor tissues are acceptable.
- Patients with EGFR mutations or ALK rearrangements must have disease progression on appropriate FDA-approved therapy for these genomic aberrations prior to enrollment.
- Disease progression on platinum-doublet chemotherapy prior to enrollment.
- At least one measurable lesion or evaluable disease. Measurable disease is defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with CT scan, as ≥20 mm by chest x-ray, or ≥10 mm with calipers by clinical exam.
- Prior treatment of cancer (chemotherapy, radiation therapy, and surgery) is allowed if completed at least 3 weeks prior to start of treatment with nintedanib and if all treatment-related toxicities are resolved.
- At least 18 years of age.
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- ECOG performance status 0-1
- Normal bone marrow and organ function as defined below:
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Hemoglobin ≥ 9.0 g/dL
- INR < 2.0
- PT and PTT < 50% of deviation from IULN
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 1.5 x IULN for patients without liver metastases and ≤ 2.5 x IULN for patients with liver metastases
- Urine protein < 2+
- Creatinine within normal institutional limits OR Creatinine clearance > 45 mL/min for patients with creatinine levels above institutional normal
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 3 months after the end of treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Who cannot join
- Prior treatment with VEGFR tyrosine kinase inhibitors.
- A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
- Currently receiving any other investigational agents, or received an investigational agent within 3 weeks of the first dose of nintedanib.
- Radiotherapy to the target lesion within the past 3 months prior to baseline imaging.
- Symptomatic brain metastases. Patients with known brain metastases are eligible if the metastases are asymptomatic and previously treated.
- Leptomeningeal disease.
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- Radiographic evidence of cavitary or necrotic tumors.
- Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to nintedanib or other agents used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure > NYHA II, active coronary artery disease, unstable angina pectoris, serious cardiac arrhythmia, uncontrolled hypertension (defined as systolic pressures > 150 mmHg or diastolic pressure > 90 mmHg), pericardial effusion, uncontrolled seizure disorder, or psychiatric illness/social situations that would limit compliance with study requirements.
- Major injuries and/or surgery with then past 4 weeks prior to the start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period.
- History of clinically significant hemorrhagic or thromboembolic event in the past 6 months.
- Known inherited predisposition to bleeding or thrombosis.
- History of cardiac infarction within the past 12 months prior to the start of study treatment.
- Receiving therapeutic anticoagulation (except 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 QD).
- Pregnant and/or breastfeeding. Patients of childbearing potential must have a negative pregnancy test within 14 days of study entry.
- Significant weight loss (> 10% of BW) within past 6 months prior to inclusion into the trial.
- Known active or chronic hepatitis B or C infection.
- Active alcohol or drug abuse.
- Gastrointestinal disorder or abnormality that would interfere with absorption of the study drug.
- Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with nintedanib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Pilot Study of Nintedanib in Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
There has been limited benefit with angiogenesis inhibitor drugs in molecularly unselected patients in non-small cell lung cancer (NSCLC). The investigators propose that patients who are molecularly selected for treatment with nintedanib based on the presence of mutations in the following genes: VEGFR1-3, PDGFR-A, PDGFR-B, FGFR1-3, and TP53, will have clinically meaningful benefit in terms of response rate (RR) and progression-free survival (PFS). Furthermore the investigators plan to correlate outcomes with specific mutations and evaluate mechanisms of resistance.
- 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 Ofev, BIBF 1120, Vargatef
| Study group | Role | What they receive |
|---|---|---|
| Nintedanib | Experimental | -Nintedanib will be administered orally at a dose of 200 mg twice daily during each 28 day cycle. Starting with cycle 64, cycles will last 12 weeks. Receives: Drug: Nintedanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate (RR)
- RR = Partial response plus complete response using RECIST 1.1
- Complete response (CR) = disappearance of all target lesions, non-target lesions, and normalization of tumor marker level
- Partial response (PR) = at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline of sum diameters
Measured: After 2 cycles of therapy (approximately Day 56)
Secondary outcomes (4)
Median Progression-free Survival (PFS)
- PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
- Progressive disease (PD) = at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, appearance of one or more non-target lesion(s) and/or unequivocal progression of existing non-target lesions
Measured: 12 months follow-up minimum
Response Rate by Mutation Type
Measured: At the time of response (approximately day 56)
Unique Genetic Variations Associated With Extreme Responders (Both Non-responders and Responders)
Correlate baseline genetic mutations with treatment response and progression of disease
Measured: Baseline and at the time of response (approximately Day 56)
Genetic Mechanisms of Secondary Resistance
Genomic analysis at time of progression after treatment with nintedanib (after response (complete response/partial response/stable disease) lasting for 6 months or longer) will provide some unique insights into mechanisms underlying acquired resistance.
Measured: At the time of progression (estimated to be 8 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2014 (estimated)
- Study start7 May 2015
- Primary completion9 Jan 2020
- Study completion23 Apr 2025
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Comprehensive Cancer Network
- Responsible party
- Sponsor
- Investigators
- Ramaswamy Govindan, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02299141
- Sponsor's protocol ID
- 201412116
- Status last verified
- Jun 2025
- First submitted
- 17 Nov 2014
- Last updated
- 24 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Waqar SN, Rawat U, Morgensztern D, et al.; A pilot study of nintedanib in molecularly selected patients with advanced non-small cell lung cancer (NSCLC) (NCT02299141). J. Clin. Oncol. 38:15_suppl, e21694-e21694; (2020) URL: https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.e21694
Auberle C, Gao F, Sloan M, Morgensztern D, Winkler L, Ward JP, Devarakonda S, Rearden TP, Govindan R, Waqar SN. A pilot study of nintedanib in molecularly selected patients with advanced non-small cell lung cancer. J Thorac Dis. 2024 Jun 30;16(6):3782-3793. doi: 10.21037/jtd-23-1717. Epub 2024 Jun 12.
PubMed 38983151
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Nintedanib in Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT02299141
- Acronym / sponsor ID
- 201412116
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Comprehensive Cancer Network
- Study start
- 7 May 2015 (actual)
- Primary completion
- 9 Jan 2020 (actual)
- Study completion
- 23 Apr 2025 (actual)
- First posted
- 24 Nov 2014 (estimated)
- Results
- Posted 21 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There has been limited benefit with angiogenesis inhibitor drugs in molecularly unselected patients in non-small cell lung cancer (NSCLC). The investigators propose that patients who are molecularly selected for treatment with nintedanib based on the presence of mutations in the following genes: VEGFR1-3, PDGFR-A, PDGFR-B, FGFR1-3, and TP53, will have clinically meaningful benefit in terms of response rate (RR) and progression-free survival (PFS). Furthermore the investigators plan to correlate outcomes with specific mutations and evaluate mechanisms of resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nintedanib | Experimental | Drug: Nintedanib-Nintedanib will be administered orally at a dose of 200 mg twice daily during each 28 day cycle. Starting with cycle 64, cycles will last 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologically confirmed diagnosis of advanced (metastatic or unresectable) NSCLC with mutations, rearrangement and fusion involving RET oncogene, or abnormalities (non-synonymous SNV or amplification) in the nintedanib target genes VEGFR1-3, TP53, PDGFR-A, PDGFR-B, and FGFR1-3. CLIA certified lab testing for nintedanib target genes using cell free DNA from peripheral blood and/or assays performed on tumor tissues are acceptable.
- Patients with EGFR mutations or ALK rearrangements must have disease progression on appropriate FDA-approved therapy for these genomic aberrations prior to enrollment.
- Disease progression on platinum-doublet chemotherapy prior to enrollment.
- At least one measurable lesion or evaluable disease. Measurable disease is defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with CT scan, as ≥20 mm by chest x-ray, or ≥10 mm with calipers by clinical exam.
- Prior treatment of cancer (chemotherapy, radiation therapy, and surgery) is allowed if completed at least 3 weeks prior to start of treatment with nintedanib and if all treatment-related toxicities are resolved.
Key exclusion criteria (21 listed)
- Prior treatment with VEGFR tyrosine kinase inhibitors.
- A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
- Currently receiving any other investigational agents, or received an investigational agent within 3 weeks of the first dose of nintedanib.
- Radiotherapy to the target lesion within the past 3 months prior to baseline imaging.
- Symptomatic brain metastases. Patients with known brain metastases are eligible if the metastases are asymptomatic and previously treated.
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: Ofev, BIBF 1120, Vargatef | Drug | Nintedanib |
Primary outcome
Response Rate (RR)
Time frame: After 2 cycles of therapy (approximately Day 56)
* RR = Partial response plus complete response using RECIST 1.1 * Complete response (CR) = disappearance of all target lesions, non-target lesions, and normalization of tumor marker level * Partial response (PR) = at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline of sum diameters
4 secondary outcomes
Median Progression-free Survival (PFS)
Time frame: 12 months follow-up minimum
Response Rate by Mutation Type
Time frame: At the time of response (approximately day 56)
Unique Genetic Variations Associated With Extreme Responders (Both Non-responders and Responders)
Time frame: Baseline and at the time of response (approximately Day 56)
Genetic Mechanisms of Secondary Resistance
Time frame: At the time of progression (estimated to be 8 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundWaqar SN, Rawat U, Morgensztern D, et al.; A pilot study of nintedanib in molecularly selected patients with advanced non-small cell lung cancer (NSCLC) (NCT02299141). J. Clin. Oncol. 38:15_suppl, e21694-e21694; (2020) URL: https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.e21694
- Derived from this study: PubMed 38983151Auberle C, Gao F, Sloan M, Morgensztern D, Winkler L, Ward JP, Devarakonda S, Rearden TP, Govindan R, Waqar SN. A pilot study of nintedanib in molecularly selected patients with advanced non-small cell lung cancer. J Thorac Dis. 2024 Jun 30;16(6):3782-3793. doi: 10.21037/jtd-23-1717. Epub 2024 Jun 12.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Ramaswamy Govindan, M.D. principal investigator
Washington University School of Medicine
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 Nintedanib in people with Carcinoma, Non-Small-Cell Lung and Non-Small Cell Lung Cancer, run by Washington University School of Medicine at 1 site 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 20 inclusion and 21 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 24 Jun 2025. 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 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 21 Feb 2021). 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?
Response Rate (RR) (time frame: After 2 cycles of therapy (approximately Day 56)). 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 NCT02299141, which also lists 2 linked publications.
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 24 Jun 2025.