Clinical trial NCT03656627: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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
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
Lead sponsor: Alliance Foundation Trials, LLC.
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-09-04
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Dose-Limiting Toxicity (DLT)
timeFrame: 48 Months
Secondary outcomes:
measure: Overall Response Rate
timeFrame: 48 Months
measure: Progression-Free Survival
timeFrame: 48 Months
measure: Overall Survival
timeFrame: 48 Months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Saint Louis Park
country: United States
facility: Metro Minnesota Community Oncology Research Consortium
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Norris Cotton Cancer Center
state: New Hampshire
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center - Thoracic Oncology Clinic
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Institute Franz Clinic
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin Clinical Science Center
state: Wisconsin
Study officials:
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