Expired Study
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Saint Louis, Missouri 63110


Purpose:

There has been limited benefit with angiogenesis inhibitor drugs when used with molecularly selected 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 (VEGFR1-3, PDGFR-A, PDGFR-B, and FGFR1-3) will have clinically meaningful benefits in terms of response rate (RR) and progression-free survival (PFS). Furthermore the investigators plan to perform exome sequencing of paired tumor (pre and post treatment) in order to better define molecular marker predictors for response and resistance.


Criteria:

Inclusion Criteria: - 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 - 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). Exclusion Criteria: - 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). - 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.


Study is Available At:


Original ID:

201412116


NCT ID:

NCT02299141


Secondary ID:


Study Acronym:


Brief Title:

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


Official Title:

A Pilot Study of Nintedanib in Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)


Overall Status:

Active, not recruiting


Study Phase:

Phase 2


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Washington University School of Medicine


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

20


Enrollment Type:

Actual


Overall Contact Information

Official Name:Ramaswamy Govindan, M.D.
Principal Investigator
Washington University School of Medicine

Study Dates

Start Date:May 7, 2015
Completion Date:August 31, 2020
Completion Type:Anticipated
Primary Completion Date:January 9, 2020
Primary Completion Type:Actual
Verification Date:January 2020
Last Changed Date:January 10, 2020
First Received Date:November 17, 2014

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Unique genetic variations associated with extreme responses (both non-responders and responders)
Time Frame:At the time of progression (estimated to be 8 months)
Safety Issues:False
Description:Unbiased exome and transcriptome sequencing performed on tumor samples at time of diagnosis in responders and non-responders will help us identify unique variations that confer susceptibility to nintedanib.
Outcome Type:Secondary Outcome
Measure:Genetic mechanisms of secondary resistance
Time Frame:At the time of progression (estimated to be 8 months)
Safety Issues:False
Description: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.
Outcome Type:Secondary Outcome
Measure:Response rate of specific genetic mutation statuses
Time Frame:At the time of progression (estimated to be 8 months)
Safety Issues:False
Description:The association between response and specific mutation status will be assessed by permutation analysis. Taking the relationship between FGFR1 expression and RR as an example, for instance, we first compute the observed test statistics, e.g., the sample me
Outcome Type:Secondary Outcome
Measure:Progression-free survival (PFS)
Time Frame:At the time of progression (estimated to be 8 months)
Safety Issues:False
Description: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
Outcome Type:Primary Outcome
Measure:Response rate (RR)
Time Frame:After 2 cycles of therapy (approximately Day 56)
Safety Issues:False
Description: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 dia

Study Interventions

Intervention Type:Drug
Name:Nintedanib
Arm Name:Nintedanib
Other Name:Ofev

Study Arms

Study Arm Type:Experimental
Arm Name:Nintedanib
Description:-Nintedanib will be administered orally at a dose of 200 mg twice daily during each 28 day cycle

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Washington University School of Medicine
Agency Class:Other
Agency Type:Collaborator
Agency Name:National Comprehensive Cancer Network

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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