Testing an Immunotherapy Anti-cancer Drug, Nivolumab, for Advanced Cancers in Patients With Autoimmune Disorders, AIM-NIVO

What this study is about

This phase Ib trial studies the side effects of nivolumab and to see how well it works alone and in combination with other treatments, such as ipilimumab, cabozantinib, platinum containing therapy, and fluoropyrimidine, in treating patients with autoimmune disorders and cancer that has spread from where it first started (primary site) to nearby tissue, lymph nodes, or distant parts of the body (advanced), to other places in the body (metastatic) or cannot removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib blocks certain proteins, which may help keep tumor cells from growing. It may also prevent the growth of new blood vessels that tumors need to grow. Cabozantinib is a type of tyrosine kinase inhibitor and a type of angiogenesis inhibitor. Chemotherapy drugs, such as platinum containing therapies and fluoropyrimidine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab alone and in combination with other treatments, including ipilimumab, cabozantinib, platinum containing therapy, or fluoropyrimidine, may be safe, tolerable, and/or effective in treating patients with autoimmune disorders and advanced, metastatic, or unresectable cancer.

Who can join (things the study team will check)

✅ You may be able to join if…

• 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, as well as the neoadjuvant or perioperative setting in which such treatment is considered standard of care or has been approved. 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 or other PD1/PD-L1 inhibitors are 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 enrolled on the study can receive Nivolumab with other FDA-approved combinations according to the FDA package insert, including, but not limited to ipilimumab, cabozantinib or chemotherapy
• 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), tubal ligation, 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. Patients can resume treatment upon termination of a pregnancy or the completion of a successful pregnancy
• 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 (Please note: Patients with more than one autoimmune disease should receive assessments for all previously diagnosed autoimmune diseases. For example, a patient with psoriasis and IBD might be enrolled in the IBD cohort. Disease assessments for both psoriasis and IBD should be obtained, as per protocol. Case report forms [CRFs] for all relevant autoimmune diseases should be utilized. However, all additional cohort requirements will be considered optional and only the assessments from the assigned cohort will be considered mandatory)
• DM/SSc-SPECIFIC INCLUSION: Patients with known SSc or DM according to updated classification criteria (Van den Hoogan et al., Arthritis Rheum 2013;65(11):2737-47; Lundberg et al., A\&R in press). Overlap features are permitted, but patients must meet criteria for a "primary diagnosis" of DM or SSc
• DM/SSc-SPECIFIC INCLUSION: Patients may be on any concurrent therapy for DM or SSc unless specifically excluded

+ 28 more criteria — see the full checklist in the app.

🚫 You may not be able to join if…

• 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
• UC-SPECIFIC EXCLUSION: Patients who have received ipilimumab treatment
• UC-SPECIFIC EXCLUSION: Prior colectomy
• UC-SPECIFIC EXCLUSION: Concurrent primary sclerosing cholangitis (PSC). Patients with PSC can be enrolled on the Other Autoimmune Diseases Cohorts
• UC-SPECIFIC EXCLUSION: Patients on empiric immunosuppressive treatment without any clinical workup
• CD-SPECIFIC EXCLUSION: Known untreated abscesses, untreated and symptomatic strictures, short gut physiology, or isolated jejunal disease
• CD-SPECIFIC EXCLUSION: Patients who have received ipilimumab treatment
• CD-SPECIFIC EXCLUSION: Patients on empiric immunosuppressive treatment without any clinical workup
• MS-SPECIFIC EXCLUSION: Patients with MS cannot have medical contraindications to gadolinium-enhanced magnetic resonance imaging (MRI)

Where this trial is running

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• Stanford Cancer Institute Palo Alto, Palo Alto, California, United States
• University of California Davis Comprehensive Cancer Center, Sacramento, California, United States
• Smilow Cancer Center/Yale-New Haven Hospital, New Haven, Connecticut, United States
• Yale University, New Haven, Connecticut, United States
• MedStar Georgetown University Hospital, Washington D.C., District of Columbia, United States
• Emory University Hospital/Winship Cancer Institute, Atlanta, Georgia, United States
• Northwestern University, Chicago, Illinois, United States
• University of Chicago Comprehensive Cancer Center, Chicago, Illinois, United States
• University of Kansas Clinical Research Center, Fairway, Kansas, United States
• HaysMed, Hays, Kansas, United States
• University of Kansas Cancer Center, Kansas City, Kansas, United States

+ 40 more sites.