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.
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