EGFR Activating MutationPhase 2NCT02949843

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

A Phase 2 study testing Chemotherapy, Immunotherapy and Laboratory Biomarker Analysis in people with EGFR Activating Mutation and Recurrent Non-Small Cell Lung Carcinoma, run by Wake Forest University Health Sciences at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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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… Read more about this study

Who is it for?: Any age
Conditions the study is for: EGFR Activating Mutation, Recurrent Non-Small Cell Lung Carcinoma, Stage IV Non-Small Cell Lung Cancer
What is being tested?: Chemotherapy, Immunotherapy and Laboratory Biomarker Analysis
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 19 participants
Where: 1 siteUnited States
Study dates: 10 Mar 2017to 12 Jan 2021
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 Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Comprehensive Cancer Center of Wake Forest University
Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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

Read the detailed description

PRIMARY OBJECTIVES:

To estimate the objective response rate among patients with high PD-L1 expressing cancers after failure of targeted therapy.

SECONDARY OBJECTIVES:

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.

Conditions: EGFR Activating Mutation, Recurrent Non-Small Cell Lung Carcinoma, Stage IV Non-Small Cell Lung Cancer
Being tested: Chemotherapy, Immunotherapy, Laboratory Biomarker Analysis, Nivolumab, Pembrolizumab
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.

ChemotherapyDrug
Also called Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General
Receive other treatment
ImmunotherapyBiological
Also called Immunologically Directed Therapy
Receive other treatment
Laboratory Biomarker AnalysisOther
Correlative studies
NivolumabBiological
Also called BMS-936558, MDX-1106, NIVO, ONO-4538
Given IV
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
Targeted Molecular TherapyDrug
Also called molecularly targeted therapy
Receive drug targeting secondary mutation
Tyrosine Kinase InhibitorDrug
Also called Protein Tyrosine Kinase Inhibitors, PTK Inhibitors, TK Inhibitors
Given PO

Study groups in NCT02949843
Study group	Role	What they receive
Arm I (nivolumab, pembrolizumab)	Experimental	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. Receives: Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Biological: Pembrolizumab
Arm II (kinase inhibitor, chemotherapy, immunotherapy)	Experimental	Patients receive tyrosine kinase inhibitor therapy PO targeting the initial oncogenic driver or other treatment for about 3 weeks. Receives: Drug: Chemotherapy; Biological: Immunotherapy; Other: Laboratory Biomarker Analysis; Drug: Tyrosine Kinase Inhibitor
Arm III (kinase inhibitor, targeted therapy, other treatment)	Experimental	Patients receive tyrosine kinase inhibitor therapy PO targeting initial oncogenic driver, a drug targeting the secondary mutation, or other treatment for about 3 weeks. Receives: Drug: Chemotherapy; Biological: Immunotherapy; Other: Laboratory Biomarker Analysis; Drug: Targeted Molecular Therapy; Drug: Tyrosine Kinase Inhibitor

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Objective Response is defined as Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). This outcome applies only to Arm I. * Complete Response (CR): Disappearance of all target lesions, * Partial Response (PR): At least a 30% decrease in the sum of the target lesions Progressive Disease (PD): At least a 20% increase in the sum of the target lesions, Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease
Measured: Up to 1 year after failure of targeted therapy

Secondary outcomes (5)

Number of Participants With 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.
Measured: Adverse events were collected following each cycle of treatment (1-4) and up to 30 days after the last dose of study treatment. The average collection time from start of treatment was 7 weeks, with a range of 3 to 11 weeks.
Number of Mutations in Secondary Genes for Patients With PD-L1 Expression < 50%
This outcome applies to only Arms II and III.
Measured: Up to 1 year after failure of targeted therapy
Objective Response Rates for Patients Without High PD-L1 Expressing Cancers
Objective response rates will be estimated in the two PD-L1 expression < 50% arms. At the time of protocol development, the intention was to estimate confidence intervals for each of these rates, and to make an exploratory comparison 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). Due to the low numbers of patients evaluable for response, these analyses were not performed.
Measured: Up to 3 years after failure of targeted therapy
Overall Survival
Estimated using Kaplan-Meier methods and survival rates will be compared using log-rank tests.
Note: Log-rank tests will not be used due to the very low sample size.
Measured: From date of progression on primary targeted treatment to death, assessed up to 3 years.
Rate of Tobacco Use and Mutation Burden Based on PD-L1 Expression at Time of Progression
Smoking History was defined as Never, Former or Current
Measured: Assessed at enrollment into study.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Mar 201712 Jan 2021

First posted31 Oct 2016 (estimated)
Study start10 Mar 2017
Primary completion8 Jan 2018
Study completion12 Jan 2021

Why it stopped: Slow accrual, closed by IRB

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.
Other trials for EGFR Activating MutationStudies of the same condition, open and under way.
More trials run by Wake Forest University Health SciencesThe 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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02949843
Sponsor's protocol ID: IRB00041150
Other IDs: NCI-2016-01589, CCCWFU 62716, P30CA012197
Status last verified: Jun 2024
First submitted: 27 Oct 2016
Last updated: 28 Jun 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 28 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02949843
Acronym / sponsor ID: IRB00041150
Conditions: EGFR Activating Mutation, Recurrent Non-Small Cell Lung Carcinoma, Stage IV Non-Small Cell Lung Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Slow accrual, closed by IRB
Enrolment: 19 participants (actual)
Lead sponsor: Wake Forest University Health SciencesUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 10 Mar 2017 (actual)
Primary completion: 8 Jan 2018 (actual)
Study completion: 12 Jan 2021 (actual)
First posted: 31 Oct 2016 (estimated)
Results: Posted 28 Jun 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

To estimate the objective response rate among patients with high PD-L1 expressing cancers after failure of targeted therapy.

SECONDARY OBJECTIVES:

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.

After completion of study treatment, patients are followed up for a minimum of 30 days.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Arm I (nivolumab, pembrolizumab)	Experimental	Other: Laboratory Biomarker Analysis, Biological: Nivolumab, Biological: PembrolizumabPatients receive nivolumab IV over 60 minutes every 2 weeks or pembrolizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.
Arm II (kinase inhibitor, chemotherapy, immunotherapy)	Experimental	Drug: Chemotherapy, Biological: Immunotherapy, Other: Laboratory Biomarker Analysis, Drug: Tyrosine Kinase InhibitorPatients receive tyrosine kinase inhibitor therapy PO targeting the initial oncogenic driver or other treatment for about 3 weeks.
Arm III (kinase inhibitor, targeted therapy, other treatment)	Experimental	Drug: Chemotherapy, Biological: Immunotherapy, Other: Laboratory Biomarker Analysis, Drug: Targeted Molecular Therapy, Drug: Tyrosine Kinase InhibitorPatients receive tyrosine kinase inhibitor therapy PO targeting initial oncogenic driver, a drug targeting the secondary mutation, or other treatment for about 3 weeks.

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

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

Key exclusion criteria (4 listed)

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

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
ChemotherapyAlso: Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, GeneralReceive other treatment	Drug	Arm II (kinase inhibitor, chemotherapy, immunotherapy), Arm III (kinase inhibitor, targeted therapy, other treatment)
ImmunotherapyAlso: Immunologically Directed TherapyReceive other treatment	Biological	Arm II (kinase inhibitor, chemotherapy, immunotherapy), Arm III (kinase inhibitor, targeted therapy, other treatment)
Laboratory Biomarker AnalysisCorrelative studies	Other	Arm I (nivolumab, pembrolizumab), Arm II (kinase inhibitor, chemotherapy, immunotherapy), Arm III (kinase inhibitor, targeted therapy, other treatment)
NivolumabAlso: BMS-936558, MDX-1106, NIVO, ONO-4538Given IV	Biological	Arm I (nivolumab, pembrolizumab)
PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV	Biological	Arm I (nivolumab, pembrolizumab)
Targeted Molecular TherapyAlso: molecularly targeted therapyReceive drug targeting secondary mutation	Drug	Arm III (kinase inhibitor, targeted therapy, other treatment)
Tyrosine Kinase InhibitorAlso: Protein Tyrosine Kinase Inhibitors, PTK Inhibitors, TK InhibitorsGiven PO	Drug	Arm II (kinase inhibitor, chemotherapy, immunotherapy), Arm III (kinase inhibitor, targeted therapy, other treatment)

Primary outcome

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 1 year after failure of targeted therapy
Objective Response is defined as Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). This outcome applies only to Arm I. * Complete Response (CR): Disappearance of all target lesions, * Partial Response (PR): At least a 30% decrease in the sum of the target lesions Progressive Disease (PD): At least a 20% increase in the sum of the target lesions, Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease

5 secondary outcomes

Number of Participants With Adverse Events Measured Using Common Terminology Criteria for Adverse Events Version 4.0
Time frame: Adverse events were collected following each cycle of treatment (1-4) and up to 30 days after the last dose of study treatment. The average collection time from start of treatment was 7 weeks, with a range of 3 to 11 weeks.
Number of Mutations in Secondary Genes for Patients With PD-L1 Expression < 50%
Time frame: Up to 1 year after failure of targeted therapy
Objective Response Rates for Patients Without High PD-L1 Expressing Cancers
Time frame: Up to 3 years after failure of targeted therapy
Overall Survival
Time frame: From date of progression on primary targeted treatment to death, assessed up to 3 years.
Rate of Tobacco Use and Mutation Burden Based on PD-L1 Expression at Time of Progression
Time frame: Assessed at enrollment into study.

Results and safety

Results posted to the registry on 28 Jun 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm I (Nivolumab, Pembrolizumab)	1	1
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)	2	1
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)	3	2

Primary outcome: 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 1 year after failure of targeted therapy. Count of participants. Unit: Participants

Measure	Arm I (Nivolumab, Pembrolizumab) n = 1	Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy) n = 0	Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment) n = 0
Partial Response	1	0	0
Stable Disease	0	0	0

Population analysed: This outcome applies only to Arm I.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected following each cycle of treatment (1-4), and up to 30 days following the last dose of study treatment. The average collection time from start of treatment was 7 weeks, with a range of 3 to 11 weeks. One patient refused additional treatment after the initial progression and was not followed for adverse events, but was followed for mortality.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm I (Nivolumab, Pembrolizumab)	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Arm II (Kinase Inhibitor, Chemotherapy, Immunotherapy)	1 of 1 (100%)	1 of 1 (100%)	2 of 2
Arm III (Kinase Inhibitor, Targeted Therapy, Other Treatment)	2 of 3 (66.7%)	3 of 3 (100%)	2 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

William Petty principal investigator

Wake Forest University Health Sciences

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 8 inclusion and 4 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: stopped early, as of the sponsor's last update on 28 Jun 2024. 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 28 Jun 2024). 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?

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 1 year after failure of targeted therapy). 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 NCT02949843.

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 28 Jun 2024.