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RecruitingNCT03816345

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

A Phase Ib Study of Nivolumab in Patients With Autoimmune Disorders and Advanced Malignancies (AIM-NIVO)

Status
Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
300 (estimated)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVES: I. 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 dermatomyositis (DM)/systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) (ulcerative colitis \[UC\] and Crohn's disease \[CD\]), multiple sclerosis (MS), Sjogren's syndrome \[SjS\], psoriasis (PsO)/psoriatic arthritis (PsA), and other autoimmune diseases. II. To assess the overall safety, and toxicities associated with the use of the anti-programmed death 1 (PD-1) antibody nivolumab and other Food and Drug Administration (FDA)-approved combinations for given oncologic indications 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: I. To evaluate the efficacy of nivolumab in terms of objective response rates (ORRs), progression-free 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. II. To observe and record anti-tumor activity. III. To propose dosing recommendations for anti-PD-1 antibodies based on the severity of the autoimmune disorder. IV. To evaluate the impact of nivolumab on the disease severity indices for: DM/SSc, RA, SLE, IBD: UC and CD, not specified (NS), MS, SjS, PsO/PsA. V. To identify biomarkers of response and toxicity. OUTLINE: Patients are assigned to 1 of 11 arms. ARM I (MONOTHERAPY): Patients may receive single agent nivolumab intravenously (IV) over 30 minutes every 4 weeks for up to 2 years for patients with metastatic indications, for up to 1 year for adjuvant indications or for up to 3 months after surgery for neoadjuvant indications in the absence of disease progression or unacceptable toxicity. ARM II (UNRESECTABLE OR METASTATIC MELANOMA): Patients receive nivolumab IV over 30 minutes every 2 or 4 weeks in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy in the absence of disease progression or unacceptable toxicity. Treatment with nivolumab may continue every 4 weeks in the absence of disease progression or unacceptable toxicity. ARM III (NEOADJUVANT TREATMENT OF RESECTABLE NON-SMALL CELL LUNG CANCER \[NSCLC\]): Patients receive nivolumab IV over 30 minutes in combination with platinum doublet therapy every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. ARM IV (METASTATIC PD-L1 POSITIVE NSCLC): Patients receive nivolumab IV over 30 minutes every 3 weeks and ipilimumab IV every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM V (METASTATIC OR RECURRENT NSCLC): Patients receive nivolumab IV over 30 minutes every 3 weeks, ipilimumab IV every 6 weeks and platinum doublet therapy every 3 weeks for up to 2 cycles of combination therapy. Treatment with nivolumab and ipilimumab repeats for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM VI (MALIGNANT PLEURAL MESOTHELIOMA): Patients receive nivolumab IV over 30 minutes every 3 weeks and ipilimumab IV every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM VII (ADVANCED RENAL CELL CARCINOMA \[RCC\]): Patients receive nivolumab IV over 30 minutes in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy in the absence of disease progression or unacceptable toxicity. Patients may continue to receive single agent nivolumab every 2 or 4 weeks in the absence of disease progression or unacceptable toxicity. Patients may optionally receive nivolumab IV every 2 or 4 weeks in combination with cabozantinib orally (PO) once daily (QD) for up to 2 years of combination therapy in the absence of disease progression or unacceptable toxicity. Treatment with single agent cabozantinib may continue in the absence of disease progression or unacceptable toxicity. ARM VIII (MICROSATELLITE INSTABILITY-HIGH \[MSI-H\] OR MISMATCH REPAIR DEFICIENT \[dMMR\] METASTATIC COLORECTAL CANCER): Patient receive nivolumab IV over 30 minutes every 2 or 4 weeks in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy in the absence of disease progression or unacceptable toxicity. Patients may continue to receive single agent nivolumab every 2 or 4 weeks in the absence of disease progression or unacceptable toxicity. ARM IX (HEPATOCELLULAR CARCINOMA \[HCC\]): Patients receive nivolumab IV over 30 minutes in combination with ipilimumab IV every 3 weeks for up to 4 doses of combination therapy. Patients may continue to receive single agent nivolumab every 2 or 4 weeks in the absence of disease progression or unacceptable toxicity. ARM X (ESOPHAGEAL SQUAMOUS CELL CARCINOMA): Patients receive nivolumab IV over 30 minutes every 2 or 4 weeks in combination with fluoropyrimidine and platinum-containing chemotherapy for up to 2 years in the absence of disease progression or unacceptable toxicity OR receive nivolumab IV every 2 or 3 weeks in combination with ipilimumab IV every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may then continue receiving fluoropyrimidine and platinum-containing chemotherapy in the absence of disease progression or unacceptable toxicity. ARM XI (GASTRIC CANCER, GASTROESOPHAGEAL JUNCTION CANCER, AND ESOPHAGEAL ADENOCARCINOMA): Patients receive nivolumab IV over 30 minutes in combination with fluoropyrimidine and platinum-containing chemotherapy every 2 or 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood, cerebrospinal fluid (CSF), tissue, stool, and urine samples throughout the trial. After completion of study treatment, patients without disease progression are followed for 100 days, and patients with disease progression are followed every 12 weeks for up to 5 years.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiospecimen CollectionUndergo collection of blood, CSF, tissue, stool and urine samples
DRUGCabozantinibGiven PO
DRUGFluoropyrimidineGiven fluoropyrimidine
BIOLOGICALIpilimumabGiven IV
BIOLOGICALNivolumabGiven IV
DRUGPlatinum CompoundGiven platinum containing chemotherapy
DRUGPlatinum DoubletGiven platinum doublet

Timeline

Start date
2019-07-16
Primary completion
2028-03-30
Completion
2028-03-30
First posted
2019-01-25
Last updated
2026-04-13

Locations

52 sites across 2 countries: United States, Canada

Regulatory

Source: ClinicalTrials.gov record NCT03816345. Inclusion in this directory is not an endorsement.