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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03656627
• Other study ID #: AFT-42
• Status: Terminated
• Phase: Phase 1
• Start date: June 27, 2019
• Est. completion date: March 18, 2021

Study information

• Verified date: February 2023
• Source: Alliance Foundation Trials, LLC.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: March 18, 2021
• Est. primary completion date: March 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Alliance Foundation Trials, LLC.	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

References & Publications (21)

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Leeb BF, Bird HA. A disease activity score for polymyalgia rheumatica. Ann Rheum Dis. 2004 Oct;63(10):1279-83. doi: 10.1136/ard.2003.011379. — View Citation

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Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995 Jan;38(1):44-8. doi: 10.1002/art.1780380107. — View Citation

Puzenat E, Bronsard V, Prey S, Gourraud PA, Aractingi S, Bagot M, Cribier B, Joly P, Jullien D, Le Maitre M, Paul C, Richard-Lallemand MA, Ortonne JP, Aubin F. What are the best outcome measures for assessing plaque psoriasis severity? A systematic review of the literature. J Eur Acad Dermatol Venereol. 2010 Apr;24 Suppl 2:10-6. doi: 10.1111/j.1468-3083.2009.03562.x. — View Citation

Romero-Diaz J, Isenberg D, Ramsey-Goldman R. Measures of adult systemic lupus erythematosus: updated version of British Isles Lupus Assessment Group (BILAG 2004), European Consensus Lupus Activity Measurements (ECLAM), Systemic Lupus Activity Measure, Revised (SLAM-R), Systemic Lupus Activity Questionnaire for Population Studies (SLAQ), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11(0 11):S37-46. doi: 10.1002/acr.20572. No abstract available. — View Citation

Seror R, Theander E, Brun JG, Ramos-Casals M, Valim V, Dorner T, Bootsma H, Tzioufas A, Solans-Laque R, Mandl T, Gottenberg JE, Hachulla E, Sivils KL, Ng WF, Fauchais AL, Bombardieri S, Valesini G, Bartoloni E, Saraux A, Tomsic M, Sumida T, Nishiyama S, Caporali R, Kruize AA, Vollenweider C, Ravaud P, Vitali C, Mariette X, Bowman SJ; EULAR Sjogren's Task Force. Validation of EULAR primary Sjogren's syndrome disease activity (ESSDAI) and patient indexes (ESSPRI). Ann Rheum Dis. 2015 May;74(5):859-66. doi: 10.1136/annrheumdis-2013-204615. Epub 2014 Jan 17. — View Citation

Sostegni R, Daperno M, Scaglione N, Lavagna A, Rocca R, Pera A. Review article: Crohn's disease: monitoring disease activity. Aliment Pharmacol Ther. 2003 Jun;17 Suppl 2:11-7. doi: 10.1046/j.1365-2036.17.s2.17.x. — View Citation

van der Heijde DM, van Leeuwen MA, van Riel PL, Koster AM, van 't Hof MA, van Rijswijk MH, van de Putte LB. Biannual radiographic assessments of hands and feet in a three-year prospective followup of patients with early rheumatoid arthritis. Arthritis Rheum. 1992 Jan;35(1):26-34. doi: 10.1002/art.1780350105. — View Citation

Walmsley RS, Ayres RC, Pounder RE, Allan RN. A simple clinical colitis activity index. Gut. 1998 Jul;43(1):29-32. doi: 10.1136/gut.43.1.29. — View Citation

Wijnands MJ, van't Hof MA, van Leeuwen MA, van Rijswijk MH, van de Putte LB, van Riel PL. Long-term second-line treatment: a prospective drug survival study. Br J Rheumatol. 1992 Apr;31(4):253-8. doi: 10.1093/rheumatology/31.4.253. — View Citation

Yee CS, Farewell VT, Isenberg DA, Griffiths B, Teh LS, Bruce IN, Ahmad Y, Rahman A, Prabu A, Akil M, McHugh N, Edwards C, D'Cruz D, Khamashta MA, Gordon C. The use of Systemic Lupus Erythematosus Disease Activity Index-2000 to define active disease and minimal clinically meaningful change based on data from a large cohort of systemic lupus erythematosus patients. Rheumatology (Oxford). 2011 May;50(5):982-8. doi: 10.1093/rheumatology/keq376. Epub 2011 Jan 18. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-Limiting Toxicity (DLT)	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	Overall Response Rate	Overall response rate is defined to be the best objective status recorded from the start of the treatment until disease progression/recurrence	48 Months
Secondary	Progression-Free Survival	Progression-free survival will be evaluated for each cohort using Kaplan-Meier estimator.	48 Months
Secondary	Overall Survival	Overall survival will be evaluated for each cohort using Kaplan-Meier estimator.	48 Months