Clinical Trials /

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

NCT03656627

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. 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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: AFT-42
  • NCT ID: NCT03656627

Conditions

  • Autoimmune Diseases
  • Non-small Cell Lung Cancer
  • Rheumatoid Arthritis
  • Psoriasis
  • Giant Cell Arteritis
  • Polymyalgia Rheumatica
  • Systemic Lupus Erythematosus
  • Crohn Disease
  • Multiple Sclerosis
  • Ulcerative Colitis

Interventions

DrugSynonymsArms
NivolumabNivolumab: Autoimmune Diseases Cohort 1

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab: Autoimmune Diseases Cohort 1ExperimentalArms 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.
  • Nivolumab
Nivolumab: Autoimmune Diseases Cohort 2ExperimentalArms 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.
  • Nivolumab

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Alliance Foundation Trials, LLC.

Trial Keywords

  • Autoimmune Diseases
  • Non-small Cell Lung Cancer
  • Ulcerative Colitis
  • Multiple Sclerosis
  • Crohn Disease
  • Systemic Lupus Erythematosus
  • Polymyalgia Rheumatica
  • Giant Cell Arteritis
  • Psoriasis
  • Rheumatoid Arthritis
  • Nivolumab
  • Opdivo

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