Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02949843
Other study ID # IRB00041150
Secondary ID NCI-2016-01589CC
Status Terminated
Phase Phase 2
First received
Last updated
Start date March 10, 2017
Est. completion date January 12, 2021

Study information

Verified date January 2021
Source Wake Forest University Health Sciences
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase II trial studies how well targeted therapy works in treating patients with incurable non-small cell lung cancer with a genetic mutation. Giving drugs that target other genetic mutations or other specific proteins may work better when a patient has cancer caused by a driver mutation and the treatment that targets that mutation stops working.


Description:

PRIMARY OBJECTIVES: I. To estimate the objective response rate among patients with high PD-L1 expressing cancers after failure of targeted therapy. SECONDARY OBJECTIVES: I. To compare the overall survival for patients receiving treatment targeting primary mutations, secondary mutations, or immunotherapy at the time of progression on tyrosine kinase inhibitor therapy. II. To assess the incidence of secondary mutations in this population according to smoking status. III. To evaluate the response rates of patients treated using these different approaches. IV. To correlate outcomes with specific secondary genetic changes. OUTLINE: Patients are assigned to 1 of 3 treatment arms. ARM I (PD-L1 >= 50%): Patients receive nivolumab intravenously (IV) over 60 minutes every 2 weeks or pembrolizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity. ARM II (PD-L1 < 50% without secondary oncogenic driver): Patients receive tyrosine kinase inhibitor therapy orally (PO) targeting the initial oncogenic driver or other treatment for about 3 weeks. ARM III (PD-L1 < 50% with secondary oncogenic driver): Patients receive tyrosine kinase inhibitor therapy PO targeting initial oncogenic driver, a drug targeting the secondary mutation, or other treatment for about 3 weeks. After completion of study treatment, patients are followed up for a minimum of 30 days.


Recruitment information / eligibility

Status Terminated
Enrollment 19
Est. completion date January 12, 2021
Est. primary completion date January 8, 2018
Accepts healthy volunteers No
Gender All
Age group N/A and older
Eligibility Inclusion Criteria: - Patients must have histologically or cytologically confirmed incurable non-small cell lung cancer that harbors an activating mutation in EGFR, MET, BRAF, V600E, RET, HER2, translocation in Alk, or translocation in ROS-1 - Patients must be receiving treatment or planning to start treatment with a tyrosine kinase inhibitor targeting the activated gene - Patients may not be receiving the treatment targeting the activated gene as part of a clinical treatment trial other than the Precision Oncology Trial - Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 - Total bilirubin =< 1.5 X institutional upper limit of normal - Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal - Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately - Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document Exclusion Criteria: - Emergent need for palliative radiation - Patients may not be receiving any other investigational agents for the treatment of non-small cell lung cancer - Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded; breastfeeding should be discontinued

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Chemotherapy
Receive other treatment
Biological:
Immunotherapy
Receive other treatment
Other:
Laboratory Biomarker Analysis
Correlative studies
Biological:
Nivolumab
Given IV
Pembrolizumab
Given IV
Drug:
Targeted Molecular Therapy
Receive drug targeting secondary mutation
Tyrosine Kinase Inhibitor
Given PO

Locations

Country Name City State
United States Comprehensive Cancer Center of Wake Forest University Winston-Salem North Carolina

Sponsors (2)

Lead Sponsor Collaborator
Wake Forest University Health Sciences National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Objective response rate in patients with high PD-L1 expressing cancers after failure of targeted therapy defined as complete or partial response according to the investigator's assessment A Simon's two-stage design will be used. Up to 3 years
Secondary Incidence of adverse events measured using Common Terminology Criteria for Adverse Events version 4.0 Toxicities for each group will be estimated and described using counts and frequencies by grade, location and relatedness. Up to 30 days after the last dose of study treatment
Secondary Incidence of mutations in secondary genes for patients with PD-L1 expression < 50% Up to 3 years
Secondary Objective response rates for patients without high PD-L1 expressing cancers Objective response rates will be estimates in the two PD-L1 expression < 50% arms. Confidence intervals for each of these rates will be estimated. An exploratory comparison will be made among the three groups comparing complete response/partial response versus stable disease/progressive disease among the groups using a Fisher's exact test (for the 2x3 table). Up to 3 years
Secondary Objective response rates for the combined population to historical controls receiving second or third line targeted agents Objective response rates will be estimates in the two PD-L1 expression < 50% arms. Confidence intervals for each of these rates will be estimated. An exploratory comparison will be made among the three groups comparing complete response/partial response versus stable disease/progressive disease among the groups using a Fisher's exact test (for the 2x3 table). Up to 3 years
Secondary Overall survival Estimated using Kaplan-Meier methods and survival rates will be compared using log-rank tests. From date of progression on primary targeted treatment to death, assessed up to 3 years
Secondary Rate of tobacco use and mutation burden based on PD-L1 expression at time of progression Up to 3 years
Secondary Smoking status defined as current, former, never Whether smoking status is related to the prevalence of any mutations identified (present/absent) will be examined using Cochran-Maentel Haenzel tests. These tests will be performed overall and then separately in the three arms. At baseline
See also
  Status Clinical Trial Phase
Completed NCT01664754 - Exemestane, Pemetrexed Disodium, and Carboplatin in Treating Post-Menopausal Women With Stage IV Non-Small Cell Lung Cancer Phase 1
Completed NCT02451930 - A Study of the Combination of Necitumumab (LY3012211) and Pembrolizumab (MK3475) in Participants With NSCLC Phase 1
Withdrawn NCT02106559 - Photodynamic Therapy During Surgery in Treating Patients With Pleural Malignancy N/A
Completed NCT02364609 - Pembrolizumab and Afatinib in Patients With Non-small Cell Lung Cancer With Resistance to Erlotinib Phase 1
Terminated NCT02495896 - Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors Phase 1
Completed NCT01935336 - Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers Phase 2
Withdrawn NCT01971489 - Buparlisib, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Advanced Solid Tumors Phase 1
Completed NCT01839955 - Erlotinib Hydrochloride and Quinacrine Dihydrochloride in Stage IIIB-IV Non-Small Cell Lung Cancer Phase 1
Terminated NCT01193868 - RO4929097 in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Recently Completed Treatment With Front-Line Chemotherapy Phase 2
Completed NCT00963807 - Trial Comparing the Use of FLT PET to Standard CT to Assess Treatment Response of Neoadjuvant Docetaxel and Cisplatin in Stage IB-IIIA Resectable NSCLC Phase 2
Completed NCT00986674 - Carboplatin and Paclitaxel Combined With Cetuximab and/or IMC-A12 in Patients With Advanced Non-Small Cell Lung Cancer Phase 2
Completed NCT00085280 - Erlotinib in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer N/A
Completed NCT00087412 - S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer Phase 2
Completed NCT00052338 - Bortezomib Plus Gemcitabine and Carboplatin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer Phase 1
Completed NCT00006929 - Suramin, Paclitaxel, and Carboplatin in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer Phase 2
Completed NCT02879994 - Pembrolizumab in Treating Patients With EGFR Mutant, Tyrosine Kinase Inhibitor Naive Advanced Non-Small Cell Lung Cancer Phase 2
Completed NCT03305380 - Radiomics to Identify Patients at Risk for Developing Pneumonitis, Differentiate Immune Checkpoint Inhibitor-induced Pneumonitis From Other Lung Inflammation and Distinguish Tumour Pseudo-progression From Real Tumour Growth
Completed NCT02728596 - S1415CD, Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER) N/A
Completed NCT02858869 - Pembrolizumab and Stereotactic Radiosurgery for Melanoma or Non-Small Cell Lung Cancer Brain Metastases Phase 1
Completed NCT02897375 - Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors Phase 1