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

Sponsor

Alliance Foundation Trials, LLC. (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03656627

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Locations

Arms

40.1

Anticipated Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Diseases Non-small Cell Lung Cancer Rheumatoid Arthritis Psoriasis Giant Cell Arteritis Polymyalgia Rheumatica Systemic Lupus Erythematosus Crohn Disease Multiple Sclerosis Ulcerative Colitis	Drug: Nivolumab	Phase 1

Detailed Description

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.

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 Design

Study Type:

Interventional

Actual Enrollment :

7 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 27, 2019

Anticipated Primary Completion Date :

Oct 31, 2022

Anticipated Study Completion Date :

Oct 31, 2022

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures

Dose-Limiting Toxicity (DLT) [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.

Secondary Outcome Measures

Overall Response Rate [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 [48 Months]
Progression-free survival will be evaluated for each cohort using Kaplan-Meier estimator.
Overall Survival [48 Months]
Overall survival will be evaluated for each cohort using Kaplan-Meier estimator.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age > 18
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Metastatic, locally advanced or recurrent NSCLC, not amenable to curative therapy.
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.
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
No limit on number of prior therapies
Ability to provide written, informed consent
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
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

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.

Non-pregnant and non-nursing.
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.
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:

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.
All adverse events (other than alopecia) from prior therapy must be resolved to Grade 1 or less.
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.
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
No active interstitial lung disease (ILD) or pneumonitis, or a history of ILD or pneumonitis requiring treatment with corticosteroids
No live vaccine within 30 days of start of study treatment
No carcinomatous meningitis or untreated CNS metastases
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
No other active malignancy
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
No active unstable angina and/or congestive heart failure, or myocardial infarction within 6 months prior to protocol participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago Medical Center	Chicago	Illinois	United States	60637
2	Marlene and Stewart Greenebaum Comprehensive Cancer Center/University of Maryland School of Medicine	Baltimore	Maryland	United States	21201
3	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
4	St. Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
5	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
6	Dartmouth Hitchcock Norris Cotton Cancer Center	Lebanon	New Hampshire	United States	03756
7	Atlantic Health System/Morristown Medical Center	Morristown	New Jersey	United States	07962
8	The Ohio State University Wexner Medical Center - Thoracic Oncology Clinic	Columbus	Ohio	United States	43210
9	Providence Cancer Institute Franz Clinic	Portland	Oregon	United States	97213
10	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
11	University of Wisconsin Clinical Science Center	Madison	Wisconsin	United States	53792