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

NCT02949843 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB00041150NCI-2016-01589CCCWFU 62716P30CA012197
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

EGFR Activating Mutation; Recurrent Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (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

  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

  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

  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%

  Up to 1 year after failure of targeted therapy

• Objective Response Rates for Patients Without High PD-L1 Expressing Cancers

  Up to 3 years after failure of targeted therapy

• Overall Survival

  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

  Assessed at enrollment into study.

Study Arms (3)

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.

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.

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.

Drug: Chemotherapy; Biological: Immunotherapy; Other: Laboratory Biomarker Analysis; Drug: Targeted Molecular Therapy; Drug: Tyrosine Kinase Inhibitor

Interventions

Chemotherapy DRUG

Receive other treatment

Also known as: Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General

Arm II (kinase inhibitor, chemotherapy, immunotherapy); Arm III (kinase inhibitor, targeted therapy, other treatment)

Immunotherapy BIOLOGICAL

Receive other treatment

Also known as: Immunologically Directed Therapy

Arm II (kinase inhibitor, chemotherapy, immunotherapy); Arm III (kinase inhibitor, targeted therapy, other treatment)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (nivolumab, pembrolizumab); Arm II (kinase inhibitor, chemotherapy, immunotherapy); Arm III (kinase inhibitor, targeted therapy, other treatment)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm I (nivolumab, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Arm I (nivolumab, pembrolizumab)

Targeted Molecular Therapy DRUG

Receive drug targeting secondary mutation

Also known as: molecularly targeted therapy

Arm III (kinase inhibitor, targeted therapy, other treatment)

Tyrosine Kinase Inhibitor DRUG

Given PO

Also known as: Protein Tyrosine Kinase Inhibitors, PTK Inhibitors, TK Inhibitors

Arm II (kinase inhibitor, chemotherapy, immunotherapy); Arm III (kinase inhibitor, targeted therapy, other treatment)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy; Immunotherapy; Adjuvants, Immunologic; Nivolumab; pembrolizumab; Molecular Targeted Therapy; Tyrosine Kinase Inhibitors

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Immunomodulation; Biological Therapy; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action

Results Point of Contact

• Title: William Petty
• Organization: Wake Forest Baptist Comprehensive Cancer Center

wpetty@wakehealth.edu

3367163313

Study Officials

• William Petty

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2016
• First Posted: October 31, 2016
• Study Start: March 10, 2017
• Primary Completion: January 8, 2018
• Study Completion: January 12, 2021
• Last Updated: June 28, 2024
• Results First Posted: June 28, 2024

Record last verified: 2024-06

Locations

US (1)