Nivolumab in Treating Patients With Metastatic Adrenocortical Cancer

• Sponsor: Northwestern University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02720484
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 10
• Locations: 2
• Arm: 1
• Actual Duration (Months): 31.1
• Patients Per Site: 5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Carcinoma in the Adrenal Cortex; Recurrent Adrenal Cortex Carcinoma; Stage III Adrenal Cortex Carcinoma; Stage IV Adrenal Cortex Carcinoma	Other: Laboratory Biomarker Analysis; Drug: Nivolumab	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

1. 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.

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

3. 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:

1. 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.

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

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Nivolumab (Anti-PD-1 Antibody) for Treatment of Metastatic Adrenocortical Carcinoma
• Actual Study Start Date: Mar 30, 2016
• Actual Primary Completion Date: Apr 17, 2017
• Actual Study Completion Date: Nov 2, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (Nivolumab) Patients receive nivolumab IV over 30 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Nivolumab; Given IV; Other Names: BMS-936558 MDX-1106 ONO-4538 Opdivo

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [From the start of treatment and every 8 weeks/2 cycles with a range of cycles attempted 1-15.]

   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..

Secondary Outcome Measures

1. Progression-free Survival (PFS) [From start of treatment and every 8 weeks/2 cycles until progressive disease or death. Median follow up of 4.5 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.

2. Overall Survival (OS) at 3 Months and 6 Months [At 3 months and 6 months from the initiation of treatment]

   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.

3. Toxicity of Nivolumab [From treatment initiation, twice every Cycle (every 14 days) while on treatment, up to 12 weeks after final dose. Range of cycles completed 1-15 (1 Cycle=28 days)]

   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

Other Outcome Measures

1. Levels of Cytokines [At baseline and at 4 weeks of treatment]

   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.

2. Levels of Peripheral Blood Lymphocyte Phenotype [At baseline and at 4 weeks of treatment]

   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.

3. PD-L1 Expression [At baseline and at 4 weeks of treatment]

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

4. PD-L2 Expression [At baseline and at 4 weeks of treatment]

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

5. Peripheral T Cell Profile Levels [At baseline and at 4 weeks of treatment]

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

6. Serum Interleukin Levels [At baseline and at 4 weeks of treatment]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have a histologically confirmed stage IV or unresectable locally advanced adrenocortical carcinoma

• Patients must have disease progressing after treatment with at least one line of therapy including mitotane and/or chemotherapy; Note: patients declining first line treatment with mitotane and/or chemotherapy based on limited efficacy are also eligible for this study

• Patients must have measurable disease according to the standard RECIST version 1.1; CT scans or magnetic resonance imaging (MRIs) used to assess the measurable disease must have been completed within 28 days prior to registration

• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3

• Leukocytes >= 2,000/mcL

• Absolute neutrophil count >= 1,500/mcL

• Hemoglobin >= 9 g/dL

• Platelets >= 100,000/mcL

• Total bilirubin =< 1.5 × institutional upper limit of normal (ULN) (except patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)

• Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine transferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN

• Serum creatinine of < 3.0 x ULN (upper limit of normal) or creatinine clearance (CrCl)

30 mL/minute (using Cockcroft/Gault formula below)

• Patients with history of central nervous system (CNS) metastases are eligible if CNS disease has been radiographically and neurologically stable for at least 6 weeks prior to study registrations and do not require corticosteroids (of any dose) for symptomatic management

• Females of childbearing potential (FOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to the start of study drug; NOTE: a FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)

• FOCBP must agree to follow instructions for method(s) of contraception (e.g. hormonal or barrier method of birth control; abstinence) for the duration of treatment with nivolumab plus 5 half-lives of nivolumab (19 weeks) plus 30 days (duration of ovulatory cycle) for a total of 23 weeks post-treatment completion

• Males who are sexually active with women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception (e.g. hormonal or barrier method of birth control; abstinence) for the duration of treatment with nivolumab plus 5 halflives of the study drug (19 weeks) plus 90 days (duration of sperm turnover) for a total of 31 weeks days post-treatment completion

• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study are not eligible

• Patients who have not recovered to =< grade 1 from adverse events due to agents administered more than 4 weeks earlier are not eligible

• Patients may not be receiving any other investigational agents

• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab are not eligible

• Patients should be excluded if they have had prior treatment with an anti-PD1 or anti-PD-L1. Please contact principal investigator, Benedito Carneiro, for specific questions on potential interactions

• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater), should be excluded; these include but are not limited to patients with a history of:

• Immune related neurologic disease

• Multiple sclerosis

• Autoimmune (demyelinating) neuropathy

• Guillain-Barre syndrome

• Myasthenia gravis

• Systemic autoimmune disease such as systemic lupus erythematosus (SLE)

• Connective tissue diseases

• Scleroderma

• Inflammatory bowel disease (IBD)

• Crohn's

• Ulcerative colitis

• Patients with a history of toxic epidermal necrolysis (TEN)

• Stevens-Johnson syndrome

• Anti-phospholipid syndrome; Note: subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll

• Any condition requiring systemic treatment with corticosteroids (> 10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug; Note: inhaled steroids and adrenal replacement steroid doses

10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; a brief (less than 3 weeks) course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by a contact allergen) is permitted

• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible

• Hypertension that is not controlled on medication (Note: hypertension is defined as blood pressure >= 140/90)

• Ongoing or active infection requiring systemic treatment

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness/social situations that would limit compliance with study requirements

• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints

• Female patients who are pregnant or nursing are not eligible

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least three years

• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) is not permitted

• Any known positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection is not permitted

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611
2	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Northwestern University
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Benedito Carneiro, MD, Northwestern University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 31, 2017

More Information

Publications

None provided.

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT02720484
• Other Study ID Numbers: NU 15E01; STU00202153; NU 15E01; P30CA060553; NCI-2016-00194
• First Posted: Mar 28, 2016
• Last Update Posted: May 1, 2019
• Last Verified: Feb 1, 2019

• Additional relevant MeSH terms: Carcinoma; Adrenocortical Carcinoma; Nivolumab

Study Results

Participant Flow

Recruitment Details	The study opened for accrual on March 22 2016 with an accrual goal of up to 33 patients. The first patient started treatment March 30, 2016. Accrual was suspended on December 5, 2016 after the first 10 patients were enrolled for Interim Analysis. The study was closed permanently on May 24 2017 with no additional patients enrolled.

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	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
Period Title: Treatment on Study
STARTED	10
Reached 1st Response/2 Cycles	7
Treated Cycle 3	4
COMPLETED	4
NOT COMPLETED	6
Period Title: Treatment on Study
STARTED	7
COMPLETED	1
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	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
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 90%
>=65 years	1 10%
Sex: Female, Male (Count of Participants)
Female	7 70%
Male	3 30%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	10 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	10 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	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..
Time Frame	From the start of treatment and every 8 weeks/2 cycles with a range of cycles attempted 1-15.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	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
Measure Participants	10
Complete Response	0 0%
Unconfirmed Partial Response	1 10%
Stable Disease	2 20%
Progressive Disease	6 60%
NE	1 10%

2. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	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.
Time Frame	From start of treatment and every 8 weeks/2 cycles until progressive disease or death. Median follow up of 4.5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	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
Measure Participants	10
Median (95% Confidence Interval) [Months]	1.8

3. Secondary Outcome

Title	Overall Survival (OS) at 3 Months and 6 Months
Description	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.
Time Frame	At 3 months and 6 months from the initiation of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	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
Measure Participants	10
3 months	79
6 months	56

4. Secondary Outcome

Title	Toxicity of Nivolumab
Description	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
Time Frame	From treatment initiation, twice every Cycle (every 14 days) while on treatment, up to 12 weeks after final dose. Range of cycles completed 1-15 (1 Cycle=28 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	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
Measure Participants	10
Rash Grade 1-2	3 30%
Nausea Grade 1-2	1 10%
Cough Grade 1-2	2 20%
Fatigue Grade 1-2	3 30%
ALT Increase Grade 1-2	1 10%
ALT Increase Grade 4	1 10%
AST Increase Grade 1-2	2 20%
AST Increase Grade 3	1 10%
Bilirubin Elevation Grade 1-2	2 20%
Hypokalemia Grade 3	1 10%
Dehydration Grade 3	1 10%
Mucositis Grade 1-2	3 30%
Tremor Grade 3	1 10%
Edema Grade 1-2	2 20%
Immune Pneumonitis Grade 3	1 10%
Immune Hepatitis Grade 3	1 10%

5. Other Pre-specified Outcome

Title	Levels of Cytokines
Description	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.
Time Frame	At baseline and at 4 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Levels of Peripheral Blood Lymphocyte Phenotype
Description	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.
Time Frame	At baseline and at 4 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	PD-L1 Expression
Description	PD-L1 expression will assist in assessing Overall response rate, PFS, and OS for this treatment.
Time Frame	At baseline and at 4 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	PD-L2 Expression
Description	PD-L2 expression will assist in assessing Overall response rate, PFS, and OS for this treatment.
Time Frame	At baseline and at 4 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Peripheral T Cell Profile Levels
Description	Peripheral T cell profile levels will assist in assessing Overall response rate, PFS, and OS for this treatment.
Time Frame	At baseline and at 4 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	Serum Interleukin Levels
Description	Serum interleukin levels will assist in assessing Overall response rate, PFS, and OS for this treatment.
Time Frame	At baseline and at 4 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Post-Hoc Outcome

Title	Progression Free Survival Rate at 3 Months and 6 Months
Description	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.
Time Frame	At 3 months and 6 months from the initiation of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	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
Measure Participants	10
3 Months	30
6 Months	20

Adverse Events

Time Frame	Adverse Events were collected for the study over approximately 1 and a half years with patients being assessed for AEs from the time of treatment initiation, at the beginning of each cycle, through 30 days post last treatment. One cycle equals 28 days and the range of cycles attempted or completed by patients was 1 to 15
Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	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
All Cause Mortality
	Treatment (Nivolumab)
	Affected / at Risk (%)	# Events
Total	5/10 (50%)
Serious Adverse Events
	Treatment (Nivolumab)
	Affected / at Risk (%)	# Events
Total	7/10 (70%)
Gastrointestinal disorders
Dehydration	1/10 (10%)
General disorders
Progressive Disease/Death	1/10 (10%)
Progressive Disease - Death	1/10 (10%)
Immune system disorders
Immune Mediated Hepatitis	1/10 (10%)
Infections and infestations
Sepsis	1/10 (10%)
Urinary Tract Infection	1/10 (10%)
Nervous system disorders
Tremor	1/10 (10%)
Altered Mental Status	1/10 (10%)
Reproductive system and breast disorders
Vaginal Hemorrhage	1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/10 (10%)
Dyspnea	1/10 (10%)
Dyspnea	1/10 (10%)
Cough	1/10 (10%)
Other (Not Including Serious) Adverse Events
	Treatment (Nivolumab)
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Blood and lymphatic system disorders
Anemia	5/10 (50%)
Cardiac disorders
Atrial Flutter	1/10 (10%)
Sinus Tachycardia	2/10 (20%)
Endocrine disorders
Adrenal Insufficiency	1/10 (10%)
Hypothyroidism	1/10 (10%)
Eye disorders
Blurred Vision	1/10 (10%)
Gastrointestinal disorders
Abdominal Pain	3/10 (30%)
Ascites	1/10 (10%)
Constipation	1/10 (10%)
Diarrhea	1/10 (10%)
Cheilitis	1/10 (10%)
Anal Mucositis	1/10 (10%)
Oral Mucositis	2/10 (20%)
Nausea	1/10 (10%)
Vomiting	1/10 (10%)
Odynophagia	1/10 (10%)
Blisters on lips	1/10 (10%)
General disorders
Edema in limbs	4/10 (40%)
Fatigue	4/10 (40%)
Fever	3/10 (30%)
Infusion Related Reaction	1/10 (10%)
Tachypnea	1/10 (10%)
Immune system disorders
Immune Mediated Hepatitis	1/10 (10%)
Infections and infestations
Mucosal Infection	1/10 (10%)
Otitis Media	1/10 (10%)
Upper Respiratory Infection	2/10 (20%)
Vaginal Infection	1/10 (10%)
Oral Candidiasis	1/10 (10%)
Investigations
Alanine Aminotransferase Increased	2/10 (20%)
Alkaline Phosphatase Increased	3/10 (30%)
Aspartate Aminotransferase Increased	5/10 (50%)
Blood Bilirubin Increased	2/10 (20%)
Creatinine Increased	3/10 (30%)
INR Increased	2/10 (20%)
Lymphocyte Count Decreased	4/10 (40%)
Lymphocyte Count Increased	1/10 (10%)
Neutrophil Count Decreased	1/10 (10%)
Weight Loss	1/10 (10%)
White Blood Cell Decreased	2/10 (20%)
Metabolism and nutrition disorders
Anorexia	1/10 (10%)
Hypercalcemia	2/10 (20%)
Hyperglycemia	9/10 (90%)
Hyperkalemia	1/10 (10%)
Hypoalbuminemia	6/10 (60%)
Hypokalemia	6/10 (60%)
Hyponatremia	5/10 (50%)
Musculoskeletal and connective tissue disorders
Back Pain	2/10 (20%)
Trunk Muscle Weakness	1/10 (10%)
Right Knee Stiffness	1/10 (10%)
Nervous system disorders
Hypersomnia	1/10 (10%)
Paresthesia	1/10 (10%)
Tremor	1/10 (10%)
Psychiatric disorders
Anxiety	1/10 (10%)
Depression	1/10 (10%)
Renal and urinary disorders
Acute Kidney Injury	1/10 (10%)
Chronic Kidney Disease	1/10 (10%)
Urinary Frequency	1/10 (10%)
Reproductive system and breast disorders
Gynecomastia	1/10 (10%)
Vaginal Hemorrhage	1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Cough	4/10 (40%)
Dyspnea	1/10 (10%)
Hypoxia	1/10 (10%)
Pharyngeal Mucositis	1/10 (10%)
Postnasal Drip	1/10 (10%)
Sneezing	1/10 (10%)
Sore Throat	1/10 (10%)
Pneumonitis	1/10 (10%)
Skin and subcutaneous tissue disorders
Maculopapular Rash	3/10 (30%)
Skin Hyperpigmentation	1/10 (10%)
Vascular disorders
Hypertension	6/10 (60%)

Limitations/Caveats

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

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.