NCI 10204 - A Phase 1b Study of Nivolumab in Patients with Autoimmune Disorders and Advanced Malignancies (AIM-NIVO)
Primary Objective
To assess the overall safety, and toxicities associated with the use of the anti-programmed death 1 (PD-1) antibody nivolumab in patients with varying severity of DM/SSc, RA, SLE, IBD (ulcerative colitis [UC] and Crohn s disease [CD]), MS, Sjogren s syndrome [SjS], Psoriasis (PsO)/Psoriatic Arthritis (PsA), and other autoimmune diseases.
Secondary Objectives
To evaluate the efficacy of nivolumab in terms of objective response rates (ORRs), progressionfree survival (PFS), and overall survival (OS) in patients with cancer and DM/SSc, RA, SLE, IBD (UC and CD), MS, SjS, PsO/PsA, and other autoimmune diseases. To observe and record anti-tumor activity.
To propose dosing recommendations for anti-PD-1 antibodies based on the severity of the
autoimmune disorder.
To evaluate the impact of nivolumab on the disease severity indices for:
DM/SSc
RA
SLE
IBD: UC and CD
NS
MS
SjS
PsO/PsA
To identify biomarkers of response and toxicity
- Rutgers Cancer Institute of New Jersey
- Principal Investigator
- Sarah Weiss MD
- Principal Investigator
Inclusion Criteria
- Patients can have either histologically confirmed malignancy that is radiologically
evaluable and metastatic or unresectable, or have a malignancy for which a
PD-1/PD-L1 inhibitor has been approved in the adjuvant setting. Eligible tumor types
include solid tumors and malignancies in which there is known evidence of clinical
activity for single agent PD-1 or PD-L1 antibodies. Nivolumab is Food and Drug
Administration (FDA)-approved for the treatment of melanoma, non-small cell lung
cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC),
gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck
cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any
solid tumor with microsatellite instability (MSI)-high status confirmed. Patients
with HL are eligible but must follow standard response criteria. Additional tumor
types may be eligible on a case by case basis upon discussion with principal
investigator (PI). Patients enrolling on the trial for adjuvant use will be
restricted to those with histology for which a PD-1/PD-L1 inhibitor has been
approved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC,
cervical cancer, and bladder cancer
- Patients who have previously received other forms of immunotherapy (high-dose [HD]
IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine
immunotherapy for at least 4 weeks before nivolumab administration. Patients who
have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks
- Age >= 18 years; children are excluded from this study but may be eligible for
future pediatric phase 1 combination trials
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky >=
60)
- Life expectancy of greater than 12 weeks
- Leukocytes >= 1,000/mcL
- Absolute neutrophil count >= 500/mcL
- Platelets >= 50,000/mcL
- Total bilirubin =< 2 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase
[SGPT]) =< 5 x institutional ULN or =< 8 x institutional ULN for patients with liver
metastases or an autoimmune disease that is contributing to the elevation of these
values
- Creatinine ULN OR glomerular filtration rate (GFR) >= 30 mL/min (if using the
Cockcroft-Gault formula)
- Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral
therapy with undetectable viral load within 6 months are eligible for this trial
- If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be
undetectable on suppressive therapy if indicated
- If history of hepatitis C virus (HCV) infection, must be treated with undetectable
HCV viral load
- Patients with new or progressive brain metastases (active brain metastases) or
leptomeningeal disease are eligible if the treating physician determines that
immediate central nervous system (CNS) specific treatment is not required and is
unlikely to be required for at least 4 weeks (or scheduled assessment after the
first cycle of treatment), and a risk-benefit analysis (discussion) by the patient
and the investigator favors participation in the clinical trial
- The effects of nivolumab on the developing human fetus are unknown. For this reason,
women of child-bearing potential (WOCBP) and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation. WOCBP receiving nivolumab
will be instructed to adhere to contraception for a period of 5 months after the
last dose of investigational product. Men receiving nivolumab and who are sexually
active with WOCBP will be instructed to adhere to contraception for a period of 7
months after the last dose of investigational product. Women of childbearing
potential must have a negative serum or urine pregnancy test (minimum sensitivity 25
IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours
prior to the start of nivolumab. Women must not be breastfeeding. Women who are not
of childbearing potential (i.e., who are postmenopausal or surgically sterile as
well as azoospermic men) do not require contraception. WOCBP is defined as any
female who has experienced menarche and who has not undergone surgical sterilization
(hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is
defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of
other biological or physiological causes. In addition, women under the age of 55
must have a documented serum follicle stimulating hormone (FSH) level less than 40
mIU/mL. These durations have been calculated using the upper limit of the half-life
for nivolumab (25 days) and are based on the protocol requirement that WOCBP use
contraception for 5 half-lives plus 30 days, and men who are sexually active with
WOCBP use contraception for 5 half-lives plus 90 days. Should a woman become
pregnant or suspect she is pregnant while she or her partner is participating in
this study, she (or the participating partner) should inform the treating physician
immediately
- Ability to understand and the willingness to sign a written informed consent
document
- Patients with more than one autoimmune disease are eligible. The treating physician
would determine which autoimmune disease is dominant and the patient would be
treated under that specific cohort
Exclusion Criteria
- Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events (AEs) due to agents administered more than 4 weeks
earlier have not resolved or stabilized. Palliative (limited-field) radiation
therapy (RT) is permitted (2 week washout from start of treatment), if all of the
following criteria are met:
- Repeat imaging demonstrates no new sites of bone metastases
- The lesion being considered for palliative radiation is not a target lesion
- Patients with prior therapy with an anti-PD-1 or anti-PD-L1
- Patients with prior allogeneic hematologic transplant
- Patients who are receiving any other anticancer investigational agents
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance
with study requirements
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.