Clinical trial NCT02949843: Targeted Therapy in Treating Patients With Incurable Non-Small Cell Lung Cancer With Genetic Mutations
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: EGFR Activating Mutation
Recurrent Non-Small Cell Lung Carcinoma
Stage IV Non-Small Cell Lung Cancer
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-10-31
Enrollment: 19
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
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
timeFrame: Up to 1 year after failure of targeted therapy
Secondary outcomes:
measure: Number of Participants With Adverse Events Measured Using Common Terminology Criteria for Adverse Events Version 4.0
timeFrame: 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.
measure: Number of Mutations in Secondary Genes for Patients With PD-L1 Expression < 50%
timeFrame: Up to 1 year after failure of targeted therapy
measure: Objective Response Rates for Patients Without High PD-L1 Expressing Cancers
timeFrame: Up to 3 years after failure of targeted therapy
measure: Overall Survival
timeFrame: From date of progression on primary targeted treatment to death, assessed up to 3 years.
measure: Rate of Tobacco Use and Mutation Burden Based on PD-L1 Expression at Time of Progression
timeFrame: Assessed at enrollment into study.
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center of Wake Forest University
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: William Petty
role: PRINCIPAL_INVESTIGATOR
References: