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Targeted Therapy in Treating Patients With Incurable Non-Small Cell Lung Cancer With Genetic Mutations

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ClinicalTrials.gov Identifier: NCT02949843
Recruitment Status : Active, not recruiting
First Posted : October 31, 2016
Last Update Posted : August 8, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief 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.

Condition or disease Intervention/treatment Phase
EGFR Activating Mutation Recurrent Non-Small Cell Lung Carcinoma Stage IV Non-Small Cell Lung Cancer Drug: Chemotherapy Biological: Immunotherapy Other: Laboratory Biomarker Analysis Biological: Nivolumab Biological: Pembrolizumab Drug: Targeted Molecular Therapy Drug: Tyrosine Kinase Inhibitor Phase 2

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Pilot Study Evaluating Strategies to Overcome Resistance at the Time of Progression for Patients With Non-small Cell Lung Cancers Harboring Major Oncogenic Drivers
Actual Study Start Date : March 10, 2017
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Arm I (nivolumab, pembrolizumab)
Patients receive nivolumab IV over 60 minutes every 2 weeks or pembrolizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Experimental: Arm II (kinase inhibitor, chemotherapy, immunotherapy)
Patients receive tyrosine kinase inhibitor therapy PO targeting the initial oncogenic driver or other treatment for about 3 weeks.
Drug: Chemotherapy
Receive other treatment
Other Names:
  • Chemo
  • Chemotherapy (NOS)
  • Chemotherapy, Cancer, General

Biological: Immunotherapy
Receive other treatment
Other Name: Immunologically Directed Therapy

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Tyrosine Kinase Inhibitor
Given PO
Other Names:
  • Protein Tyrosine Kinase Inhibitors
  • PTK Inhibitors
  • TK Inhibitors

Experimental: Arm III (kinase inhibitor, targeted therapy, other treatment)
Patients receive tyrosine kinase inhibitor therapy PO targeting initial oncogenic driver, a drug targeting the secondary mutation, or other treatment for about 3 weeks.
Drug: Chemotherapy
Receive other treatment
Other Names:
  • Chemo
  • Chemotherapy (NOS)
  • Chemotherapy, Cancer, General

Biological: Immunotherapy
Receive other treatment
Other Name: Immunologically Directed Therapy

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Targeted Molecular Therapy
Receive drug targeting secondary mutation
Other Name: molecularly targeted therapy

Drug: Tyrosine Kinase Inhibitor
Given PO
Other Names:
  • Protein Tyrosine Kinase Inhibitors
  • PTK Inhibitors
  • TK Inhibitors




Primary Outcome Measures :
  1. 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 [ Time Frame: Up to 3 years ]
    A Simon's two-stage design will be used.


Secondary Outcome Measures :
  1. Incidence of adverse events measured using Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days after the last dose of study treatment ]
    Toxicities for each group will be estimated and described using counts and frequencies by grade, location and relatedness.

  2. Incidence of mutations in secondary genes for patients with PD-L1 expression < 50% [ Time Frame: Up to 3 years ]
  3. Objective response rates for patients without high PD-L1 expressing cancers [ Time Frame: Up to 3 years ]
    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).

  4. Objective response rates for the combined population to historical controls receiving second or third line targeted agents [ Time Frame: Up to 3 years ]
    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).

  5. Overall survival [ Time Frame: From date of progression on primary targeted treatment to death, assessed up to 3 years ]
    Estimated using Kaplan-Meier methods and survival rates will be compared using log-rank tests.

  6. Rate of tobacco use and mutation burden based on PD-L1 expression at time of progression [ Time Frame: Up to 3 years ]
  7. Smoking status defined as current, former, never [ Time Frame: At baseline ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02949843


Locations
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United States, North Carolina
Comprehensive Cancer Center of Wake Forest University
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Investigators
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Principal Investigator: William Petty Wake Forest University Health Sciences

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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT02949843     History of Changes
Other Study ID Numbers: IRB00041150
NCI-2016-01589 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CCCWFU 62716 ( Other Identifier: Comprehensive Cancer Center of Wake Forest University )
P30CA012197 ( U.S. NIH Grant/Contract )
First Posted: October 31, 2016    Key Record Dates
Last Update Posted: August 8, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Nivolumab
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents