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.
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
Drug | Synonyms | Arms |
---|
Nivolumab | | Nivolumab: 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
Name | Type | Description | Interventions |
---|
Nivolumab: Autoimmune Diseases Cohort 1 | Experimental | 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. | |
Nivolumab: Autoimmune Diseases Cohort 2 | Experimental | 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. | |
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: | Active, not 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
Last Updated
June 18, 2021