Neoplasms

All Conditions

Symptoms and General Pathology

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Recurrence

Adrenocortical Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Adrenal Cortex Neoplasms

Adrenal Gland Neoplasms

Endocrine Gland Neoplasms

Adrenal Cortex Diseases

Adrenal Gland Diseases

Endocrine System Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Nivolumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive nivolumab IV over 30 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Benedito Carneiro, MD

The primary objective will be to assess overall response rate of nivolumab in patients with metastatic or locally advanced adrenocortical carcinoma. Nivolumab was recently approved by U.S. Food and Drug Administration (FDA) for the treatment of advanced melanoma, non-small cell lung cancer and renal cell carcinoma. It is considered investigational for the treatment of advanced or refractory adrenocortical carcinoma. "Investigational" means that the drug is not approved by the USFDA or not approved for the indication under investigation. Nivolumab could shrink adrenocortical carcinoma but it could also cause side effects. Researchers hope to learn if the study drug will shrink the cancer and hopefully to relieve symptoms that are related to the cancer.

PRIMARY OBJECTIVES:

I. To assess overall response rate of nivolumab in patients with metastatic or locally advanced adrenocortical carcinoma (ACC).

SECONDARY OBJECTIVES:

I. To assess the progression free survival defined as time from date of first nivolumab infusion until date of death or evidence of progression of disease as assessed by computed tomography (CT) imaging every 8 weeks according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1.

II. To assess the overall survival defined as time from date of first nivolumab infusion until death of patients with metastatic or locally advanced ACC.

III. To assess the safety and tolerability profile of nivolumab described by number, frequency, and severity of adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.3 assessed every 2 weeks while patients are on therapy.

TERTIARY OBJECTIVES:

I. To assess the overall response rate, progression free survival and overall survival according to tumor programmed cell death 1 ligand 1 (PD-L1) and programmed cell death 1 ligand 2 (PD-L2) expression.

II. To assess the overall response rate, progression free survival and overall survival according to serum interleukin levels and peripheral T cell profile levels.

III. To measure humoral and cellular responses to tumor antigens on serum samples by measuring the levels of cytokines (ie, interleukin \[IL\] -2, IL-6, IL-8, IL-10, IL-18, interferon \[IFN\] gamma and tumor necrosis factor \[TNF\]-alpha) and peripheral blood lymphocyte phenotype.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity, or withdrawal of consent.

After completion of study treatment, patients are followed up every 3 months for up to 2 years.

Nivolumab in Treating Patients With Metastatic Adrenocortical Cancer

Phase II Study of Nivolumab (Anti-PD-1 Antibody) for Treatment of Metastatic Adrenocortical Carcinoma

Humoral and cellular responses to tumor antigens on serum samples will be evaluated by measuring the levels of cytokines (ie, IL-2, IL-6, IL-8, IL-10, IL-18, IFN gamma and TNF-alpha). Potential correlations between differential measures of response and the toxicity and efficacy of nivolumab will be explored.

Humoral and cellular responses to tumor antigens on serum samples will be evaluated by measuring the levels of peripheral blood lymphocyte phenotype. Potential correlations between differential measures of response and the toxicity and efficacy of nivolumab will be explored.

PD-L1 expression will assist in assessing Overall response rate, PFS, and OS for this treatment.

PD-L2 expression will assist in assessing Overall response rate, PFS, and OS for this treatment.

Peripheral T cell profile levels will assist in assessing Overall response rate, PFS, and OS for this treatment.

Serum interleukin levels will assist in assessing Overall response rate, PFS, and OS for this treatment.

Overall Response Rate of nivolumab treatment for patients with metastatic adrenocortical carcinoma will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI scans every 8 weeks:

Complete Response (CR) = disappearance of all target lesions. Partial Response (PR) \>=30% decrease in the sum of the longest diameter of target lesions (should be confirmed 8 weeks after initial response otherwise considered unconfirmed PR).

Stable Disease, neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.

Progressive Disease, defined as having at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions..

Progression Free Survival (PFS) of nivolumab treatment in patients with metastatic adrenocortical carcinoma is defined as the duration of time from start of treatment to time of documented progression or death, whichever comes first. It will measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI scans every 8 weeks.

Overall Survival (OS) of nivolumab treatment in patients with metastatic adrenocortical carcinoma and will be defined as the duration of time from treatment initiation until death. OS will be assessed as the percentage of patients alive at 3 months and at 6 months from initiation of treatment on study.

Safety and tolerability profile of Nivolumab will be assessed by describing by number, frequency, and severity of Adverse Events (AEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.3. All AEs that were considered related to Nivolumab were collected and are shown below. Patients with multiple events in the same category are counted only once in that category. Patients with events in more than one category are counted in each of those categories. Categories with no events are not shown.

In general AEs will be graded according to the following:

Grade 1 = Mild AE Grade 2= Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE

National Cancer Institute (NCI)

Northwestern University

Patients receive nivolumab IV over 30 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Nivolumab: Given IV

Treatment (Nivolumab)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

The study did not meet its first stage requirements of Interim analysis.

Devalingam Mahalingam

Complete Response

Unconfirmed Partial Response

Stable Disease

Progressive Disease

All patients that received one dose of nivolumab were evaluable for this objective.

Overall Response Rate

Progression-free Survival (PFS)

3 months

6 months

Overall Survival (OS) at 3 Months and 6 Months

Rash Grade 1-2

Nausea Grade 1-2

Cough Grade 1-2

Fatigue Grade 1-2

ALT Increase Grade 1-2

ALT Increase Grade 4

AST Increase Grade 1-2

AST Increase Grade 3

Bilirubin Elevation Grade 1-2

Hypokalemia Grade 3

Dehydration Grade 3

Mucositis Grade 1-2

Tremor Grade 3

Edema Grade 1-2

Immune Pneumonitis Grade 3

Immune Hepatitis Grade 3

Toxicity of Nivolumab

Levels of Cytokines

Levels of Peripheral Blood Lymphocyte Phenotype

PD-L1 Expression

PD-L2 Expression

Peripheral T Cell Profile Levels

Serum Interleukin Levels

3 Months

6 Months

Progression Free Survival (PFS) of nivolumab treatment in patients with metastatic adrenocortical carcinoma is defined as the duration of time from start of treatment to time of documented progression or death, whichever comes first. It will measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI scans every 8 weeks. PRS rate at 3 months and 6 months will be calculated as the percentage of patients that have not yet progressed at that timepoint.

Progression Free Survival Rate at 3 Months and 6 Months

Treatment on Study

Follow Up for 2 Years

Spots Global Cancer Trial Database for metastatic carcinoma in the adrenal cortex