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

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ClinicalTrials.gov Identifier: NCT03656627
Recruitment Status : Recruiting
First Posted : September 3, 2018
Last Update Posted : October 14, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Alliance Foundation Trials, LLC.

Tracking Information
First Submitted Date  ICMJE August 31, 2018
First Posted Date  ICMJE September 3, 2018
Last Update Posted Date October 14, 2019
Actual Study Start Date  ICMJE June 27, 2019
Estimated Primary Completion Date October 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03656627 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 31, 2018)
  • 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
  • Progression-Free Survival [ Time Frame: 48 Months ]
    Progression-free survival will be evaluated for each cohort using Kaplan-Meier estimator.
  • Overall Survival [ Time Frame: 48 Months ]
    Overall survival will be evaluated for each cohort using Kaplan-Meier estimator.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer and Pre-existing Autoimmune Disease
Official Title  ICMJE Safety, Activity, and Pharmacology of Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer and Pre-existing Autoimmune Disease
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Autoimmune Diseases
  • Non-small Cell Lung Cancer
  • Rheumatoid Arthritis
  • Psoriasis
  • Giant Cell Arteritis
  • Polymyalgia Rheumatica
  • Systemic Lupus Erythematosus
  • Crohn Disease
  • Multiple Sclerosis
  • Ulcerative Colitis
Intervention  ICMJE 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.

Study Arms  ICMJE
  • 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.

    Intervention: Drug: Nivolumab
  • 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.

    Intervention: Drug: Nivolumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 31, 2018)
72
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2022
Estimated Primary Completion Date October 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Director of Project Management 617-525-8627 info@alliancefoundationtrials.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03656627
Other Study ID Numbers  ICMJE AFT-42
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Alliance Foundation Trials, LLC.
Study Sponsor  ICMJE Alliance Foundation Trials, LLC.
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE Not Provided
PRS Account Alliance Foundation Trials, LLC.
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP