Nivolumab in Treating Patients With Advanced Metastatic Non-small Cell Lung Cancer

NCT03121417 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: IRB00090380NCI-2016-02017Winship3286-16-CA209-461
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial is studying blood and tumor tissue from patients with advanced non-small cell lung cancer who are treated with nivolumab to better understand how nivolumab works. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread by turning on the immune system (T cells). We want to study the effects of nivolumab on the immune system (T cells) by collecting blood samples and samples from patients' tumors.

Conditions

Recurrent Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  The response rates to nivolumab treatment will be compared between two groups of patients (positive vs negative) stratified by the status of PD-1+Ki-67+CD8 T cells. The objective disease response (ORR) is determined radiographically by Response Criteria in Solid Tumors version 1.1 (RECIST 1.1).

  Up to 3 years after study start

Secondary Outcomes (3)

• Change in T cell population in the peripheral blood assessed by flow cytometry

  Baseline up to 16 weeks after study start

• Progression Free Survival (PFS)

  Every 12 weeks until disease progression or up to 3 years

• Overall survival (OS)

  Every 3 months up to 3 years after drug discontinuation

Study Arms (1)

Treatment (nivolumab)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unexpected toxicity

Biological: Nivolumab

Interventions

Nivolumab BIOLOGICAL

240 mg given IV

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

Treatment (nivolumab)

Eligibility Criteria

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

You may qualify if:

• Subjects must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent form in accordance with regulatory and institutional guidelines; this must be obtained before the performance of any protocol related procedures that are not part of normal subject care
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study
• Histologically confirmed stage IV or recurrent non-small cell lung cancer (NSCLC) per the 7th International Association for the Study of Lung Cancer classification with squamous or non-squamous histology
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2; patients with PS 2 are being included as the primary endpoint of the study is correlation of blood based biomarkers with response; nivolumab is currently approved for both squamous and non-squamous NSCLC
• Disease progression following frontline platinum doublet therapy given for metastatic or recurrent disease; there is no restriction on prior lines of therapy following receipt of initial platinum doublet therapy
• Continuation maintenance therapy following platinum-based chemotherapy will not be considered as a separate line of therapy
• Prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation therapy given for locally advanced disease is considered first-line platinum therapy only if recurrent disease developed within 6 months of completing therapy
• Patients with activating epidermal growth factor receptor (EGFR) mutations must have received an EGFR tyrosine kinase inhibitor directed therapy prior to platinum therapy
• Patients with anaplastic lymphoma kinase (ALK) translocations must have received an ALK tyrosine kinase inhibitor directed therapy prior to platinum therapy
• Prior systemic chemotherapy or other investigational therapy must have been completed at least two weeks prior to administration of nivolumab
• Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Subject willing to undergo biopsy prior to treatment with investigational therapy for fresh tissue immune cell analysis and would consider biopsy at disease progression (progression biopsy is not mandated); biopsy should be obtained with core needle; fine needle aspirates are not sufficient; if prior archival tissue is available, it should be submitted
• Prior palliative radiotherapy must have been completed at least 2 weeks prior to registration; subjects with symptomatic tumor lesions at baseline that may require palliative radiotherapy within 4 weeks of randomization are strongly encouraged to receive palliative radiotherapy prior to randomization
• White blood cell (WBC) ≥ 2000/µL
• Neutrophils ≥ 1500/µL

You may not qualify if:

• Subjects with untreated central nervous system (CNS) metastases or carcinomatous meningitis are excluded
• Subjects with CNS metastases are only eligible if the CNS metastases are treated with radiotherapy and/or surgery and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment); in addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent)
• Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before registration
• Subjects with an active, known or suspected autoimmune disease; subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of registration; inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
• Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
• Ongoing or planned administration of anti-cancer therapies other than nivolumab
• Anti-cancer therapy, including an investigational agent, less than 14 days prior to the first dose of nivolumab
• Prisoners or subjects who are involuntarily incarcerated
• Any other serious or uncontrolled medical disorder, active infection, physical exam finding, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a subject's ability to comply with the study requirements, substantially increase risk to the subject, or impact the interpretability of study results
• Drugs with a predisposition to hepatoxicity should be used with caution

Sponsors & Collaborators

• Emory University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Rathi Pillai, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 17, 2017
• First Posted: April 20, 2017
• Study Start: July 21, 2017
• Primary Completion: March 9, 2019
• Study Completion: March 9, 2019
• Last Updated: May 21, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)