Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer and Pre-existing Autoimmune Disease

February 14, 2023 updated by: Alliance Foundation Trials, LLC.

Safety, Activity, and Pharmacology of Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer and Pre-existing Autoimmune Disease

The purpose of this study is to explore the safety, tolerability and activity of Nivolumab, a PD-1 inhibitor, in cohorts of patients with autoimmune disease. Two cohorts of patients will be enrolled, based on autoimmune disease type.

Patients will be screened within 28 days prior to the start of dosing. Eligible patients will be enrolled in either of the two cohorts. Patients will receive treatment every two weeks, in an outpatient setting. One cycle is a 28-day period, with Nivolumab given on days 1 and 15 of a 28-day cycle. Subjects will be permitted to continue treatment beyond initial RECIST 1.1.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to explore the safety, tolerability and activity of Nivolumab, a PD-1 inhibitor, in cohorts of patients with autoimmune disease. Two cohorts of patients will be enrolled, based on autoimmune disease type as outlined below. Entry into cohorts 1 and 2 will start simultaneously and enroll independently.

Cohort 1: Rheumatoid arthritis, psoriasis, giant cell arteritis/polymyalgia rheumatica, systemic lupus erythematosis Cohort 2: Other autoimmune diseases (ulcerative colitis, Crohn's disease, multiple sclerosis). Patients must be discussed with PI prior to enrollment.

Patients will be screened within 28 days prior to the start of dosing. Eligible patients will be enrolled in either of the two cohorts. Patients will receive treatment every two weeks, in an outpatient setting. One cycle is a 28-day period, with Nivolumab given on days 1 and 15 of a 28-day cycle. Subjects will be permitted to continue treatment beyond initial RECIST 1.1. For each cohort, all patients will be dosed at 240 mg IV. There will be no dose de-escalation or escalation from this dose level.

Participants will be followed with telephone follow up for two years after removal from protocol therapy or until death, whichever occurs first. Phone calls will be placed every six months and survival follow up obtained. Participants removed from protocol therapy for unacceptable adverse event(s) will be followed until resolution or stabilization of the adverse event, in addition to the follow up for two years after removal from protocol therapy or until death, whichever occurs first.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • St. Joseph Mercy Hospital
    • Minnesota
      • Saint Louis Park, Minnesota, United States, 55416
        • Metro Minnesota Community Oncology Research Consortium
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Norris Cotton Cancer Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Wexner Medical Center - Thoracic Oncology Clinic
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Cancer Institute Franz Clinic
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Hillman Cancer Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Clinical Science Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age > 18
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  3. Metastatic, locally advanced or recurrent NSCLC, not amenable to curative therapy.
  4. Patients should have received at least one platinum-based chemotherapy regimen for recurrent or metastatic disease or have received platinum-based chemotherapy as part of adjuvant or neoadjuvant therapy and experienced progression of disease within 6 months of completing therapy.
  5. Patients with tumor genetic alterations such as EGFR, ALK, ROS1 or BRAF V600E alterations for which there is FDA-approved targeted therapy must have been treated with the appropriate targeted inhibitors in prior therapy
  6. No limit on number of prior therapies
  7. Ability to provide written, informed consent
  8. Patients must be on a stable regimen of treatment for their autoimmune condition without need for addition of new medications or escalating doses of preexisting medications in the previous 12 weeks prior to study entry

  9. In addition, patients with the following autoimmune diseases must have baseline disease activity scores as follows (please see Appendix A):

    • For rheumatoid arthritis: DAS28 < 5.1
    • For polymyalgia rheumatica: PMR-AS < 17
    • For Sjogrens: ESSDAI < 14
    • For ulcerative colitis: SSCAI < 5
    • For Crohn's disease: CDAI < 450
    • For systemic lupus erythroderma: SLEDAI-2K < 20
    • For multiple sclerosis: EDSS < 5.5

  10. Adequate organ and marrow function as defined by:

    • absolute neutrophil count ≥ 1,500/mcL
    • platelets ≥ 100,000/mcL
    • total bilirubin ≤ 2.5 × institutional upper limit of normal
    • AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal, OR
    • AST(SGOT)/ALT(SGPT ) ≤5 × institutional upper limit of normal if liver metastases are present
    • Creatinine within normal institutional limits OR
    • Creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
  11. Non-pregnant and non-nursing.
  12. Women of childbearing potential (WOCBP) must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses > 1 year.
  13. Male patients must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.

Exclusion Criteria:

  1. No chemotherapy or radiotherapy within two weeks of study entry. Prior targeted therapy is allowed as long as at least 5 half-lives have elapsed since last dose.
  2. All adverse events (other than alopecia) from prior therapy must be resolved to Grade 1 or less.
  3. Patients who are known to be HIV positive are excluded due to the known immunologic alterations associated with the disease. HIV testing is not required.
  4. No uncontrolled intercurrent illness such as active infection, or psychiatric illness or social situation that in the judgment of the investigator would limit compliance with study requirements
  5. No active interstitial lung disease (ILD) or pneumonitis, or a history of ILD or pneumonitis requiring treatment with corticosteroids
  6. No live vaccine within 30 days of start of study treatment
  7. No carcinomatous meningitis or untreated CNS metastases
  8. No history of significant cardiac disease or presence of an abnormality in electrocardiograms that, in the investigator's opinion, is medically exclusionary or clinically meaningful
  9. No other active malignancy
  10. No known history of or positivity for active hepatitis B or C. HBV DNA and/or HCV RNA must be undetectable and HBsAg must be negative at the time of screening
  11. No active unstable angina and/or congestive heart failure, or myocardial infarction within 6 months prior to protocol participation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nivolumab: Autoimmune Diseases Cohort 1

Arms determined by autoimmune type. First cohort consists of patients with:

Rheumatoid arthritis, psoriasis, giant cell arteritis/polymyalgia rheumatica, systemic lupus erythematosis

If a patient has more than one autoimmune condition, if all the conditions are within either cohort 1 or 2 above, the patient will be assigned to that cohort. If the patient has conditions from both cohort 1 and 2, the patient will be grouped in cohort 2.
Drug: Nivolumab

Nivolumab will be given as an IV infusion every two weeks, in an outpatient setting. One cycle is a 28-day period, with Nivolumab given on days 1 and 15 of a 28-day cycle.

For each cohort, all patients will be dosed at 240 mg IV. There will be no dose de-escalation or escalation from this dose level.
Experimental: Nivolumab: Autoimmune Diseases Cohort 2

Arms determined by autoimmune type. Second cohort consists of patients with:

Other autoimmune diseases (ulcerative colitis, Crohn's disease, multiple sclerosis). Patients must be discussed with PI prior to enrollment.

If a patient has more than one autoimmune condition, if all the conditions are within either cohort 1 or 2 above, the patient will be assigned to that cohort. If the patient has conditions from both cohort 1 and 2, the patient will be grouped in cohort 2.
Drug: Nivolumab

Nivolumab will be given as an IV infusion every two weeks, in an outpatient setting. One cycle is a 28-day period, with Nivolumab given on days 1 and 15 of a 28-day cycle.

For each cohort, all patients will be dosed at 240 mg IV. There will be no dose de-escalation or escalation from this dose level.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-Limiting Toxicity (DLT)
Time Frame: 48 Months
The DLT determination period is the first six weeks after cycle 1 day 1. Dose limiting toxicities are further defined in the trial protocol.
48 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: 48 Months
Overall response rate is defined to be the best objective status recorded from the start of the treatment until disease progression/recurrence
48 Months
Progression-Free Survival
Time Frame: 48 Months
Progression-free survival will be evaluated for each cohort using Kaplan-Meier estimator.
48 Months
Overall Survival
Time Frame: 48 Months
Overall survival will be evaluated for each cohort using Kaplan-Meier estimator.
48 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance Foundation Trials, LLC.

Collaborators

Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 27, 2019

Primary Completion (Actual)

March 18, 2021

Study Completion (Actual)

March 18, 2021

Study Registration Dates

First Submitted

August 31, 2018

First Submitted That Met QC Criteria

August 31, 2018

First Posted (Actual)

September 4, 2018

Study Record Updates

Last Update Posted (Actual)

February 15, 2023

Last Update Submitted That Met QC Criteria

February 14, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AFT-42

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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