Nintedanib in Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer

NCT02299141 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 201412116
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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, 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.

Conditions

Carcinoma, Non-Small-Cell Lung; Nonsmall Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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

  After 2 cycles of therapy (approximately Day 56)

Secondary Outcomes (4)

• Median Progression-free Survival (PFS)

  12 months follow-up minimum

• Response Rate by Mutation Type

  At the time of response (approximately day 56)

• Unique Genetic Variations Associated With Extreme Responders (Both Non-responders and Responders)

  Baseline and at the time of response (approximately Day 56)

• Genetic Mechanisms of Secondary Resistance

  At the time of progression (estimated to be 8 months)

Study Arms (1)

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.

Drug: Nintedanib

Interventions

Nintedanib DRUG

Also known as: Ofev, BIBF 1120, Vargatef

Nintedanib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (2)

• 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

  BACKGROUND

• 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.

  PMID: 38983151 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

nintedanib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Ramaswamy Govindan
• Organization: Washington University School of Medicine

rgovindan@wustl.edu

314-362-5654

Study Officials

• Ramaswamy Govindan, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2014
• First Posted: November 24, 2014
• Study Start: May 7, 2015
• Primary Completion: January 9, 2020
• Study Completion: April 23, 2025
• Last Updated: June 24, 2025
• Results First Posted: February 21, 2021

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)