Ipilimumab in Combination With Androgen Suppression Therapy in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

• Sponsor: OHSU Knight Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01498978
• Collaborator: Bristol-Myers Squibb (Industry), Oregon Health and Science University (Other)
• Enrollment: 10
• Locations: 2
• Arm: 1
• Actual Duration (Months): 83.4
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies how well ipilimumab works when given together with androgen suppression therapy in treating patients with hormone-resistant prostate cancer that has spread to other parts of the body. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumors to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Androgen can cause the growth of prostate cancer. Androgen deprivation therapy may stop the adrenal glands from making androgen. Giving ipilimumab together with androgen suppression therapy may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Prostate; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage IV Prostate Cancer	Biological: ipilimumab; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Proportion of patients who achieve an undetectable prostate-specific antigen (PSA) (=< 0.2 ng/ml) after initiation of ipilimumab therapy.

SECONDARY OBJECTIVES:

1. Time to PSA progression. II. Time to progression by any measure. III. Maximum percentage of PSA reduction in each patient. IV. Number of patients with immune related adverse events (IRAEs) and correlation of these with complete PSA response, time to progression, and T cell measurements.

2. Measures of T cell response to therapy with flow cytometry. VI. Response in measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

3. Time to death from any cause. VIII. To examine correlative biomarkers and their relationship to clinical outcomes. Potential biomarkers include, but are not limited to C-reactive protein (CRP), insulin-like growth factor (IGF)-1 and -2, or follicle stimulating hormone (FSH).

4. Bank samples for future molecular correlative studies, biomarker, or other studies.

OUTLINE:

Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression then receive maintenance ipilimumab IV once every 3 months for 4 additional doses.

After completion of study treatment, patients are followed up every 6 months for up to 5 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: A Phase II Study of CTLA Blockade by Ipilimumab Plus Androgen Suppression Therapy in Patients With an Incomplete Response to AST Alone for Metastatic Prostate Cancer
• Actual Study Start Date: Feb 6, 2012
• Actual Primary Completion Date: Feb 28, 2017
• Actual Study Completion Date: Jan 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (ipilimumab) Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression then receive maintenance ipilimumab IV once every 3 months for 4 additional doses.	Biological: ipilimumab; Given IV; Other Names: anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody MDX-010 MDX-CTLA-4 monoclonal antibody CTLA-4 ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Who Achieve an Undetectable PSA (=< 0.2 ng/ml) [Up to 5 years]

   Undetectable PSA (prostate-specific antigen) defined as PSA ≤ 0.2 ng/mg after initiation of ipilimumab therapy. Provided with the exact 95% confidence interval. PSA response as recommended by the Prostate Cancer Clinical Trials Working Group (PCWG2) definitions. Percentage can take on values between 0% and 100%.

Secondary Outcome Measures

1. Time to PSA Progression [Up to 5 years]

   PSA (prostate-specific antigen) progression defined as a PSA increase of >= 25% and at least 2 ng/mL from baseline or nadir PSA achieved, confirmed by a second measurement at least three weeks later Time to PSA progression is calculated as the time from Day 1 of combination therapy to first PSA measurement of >= 25% increase and at least 2 ng/mL above the nadir and confirmed by a second measurement at least three weeks later. For subjects without a PSA decline from baseline, time to PSA progression is calculated as the time from Day 1 of combination therapy to first PSA measurement of >= 25% increase and at least 2 ng/mL increase from baseline after 12 weeks and confirmed by a second measurement at least three weeks later. Outcome is reported as median time to event determined by the Kaplan Meier method with 95% confidence interval.

2. Time to Progression by Any Measure [Up to 5 years]

   Time to progression is calculated from Day 1 of combination therapy to first evidence of progression by any measure (PSA, Measurable Disease or Clinical Progression). Outcome is reported as median time to event determined by the Kaplan Meier method with 95% confidence interval.

3. Time to Death From Any Cause [Up to 5 years]

   Time to death is calculated from Day 1 of combination therapy to death from any cause. Outcome is reported as median time to event determined by the Kaplan Meier method with 95% confidence interval.

4. Number of Patients With IRAEs [Up to 6 months]

   Immune-Related Adverse Events (IRAEs) are defined as an adverse event (AE) of unknown etiology associated with drug exposure and consistent with an immune phenomenon Tabulated for each treatment group and summarized according to major organ categories of the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

5. Correlation Between IRAE and PSA Progression. [Up to 5 years]

   Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event. PSA (prostate-specific antigen) Progression is defined as a PSA increase of >= 25% and at least 2 ng/mL from Baseline, or Nadir PSA Achieved, confirmed by a second measurement at least three weeks later. The correlation between IRAEs and clinical outcomes will be evaluated using logistic regression for binary endpoints and Cox regression for the time to event outcomes. Due to sample size, regression is not feasible. Instead, correlation will be assessed by Fishers Exact test of association.

6. Correlation of IRAEs With Ratio of T Regulatory Cells to T Effector Cells [Up to day 1 of course 4]

   Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event. Raw T cells data was collected, but has not been analyzed by the lab and will not be done due to constraints. No data displayed because Outcome Measure has zero total participants analyzed.

7. Correlation Between IRAEs and Immune Response [Up to day 1 of course 4]

   Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event. Outcome not evaluated due to technical challenges collecting the data, and lack of budget and personnel to complete the analysis. No data displayed because Outcome Measure has zero total participants analyzed.

8. Correlation Between IRAE and Radiographic Progression. [Up to 5 years]

   Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event. Radiographic progression is progression determined by scan. The correlation between IRAEs and clinical outcomes will be evaluated using logistic regression for binary endpoints and Cox regression for the time to event outcomes. Due to sample size, regression is not feasible. Instead, correlation will be assessed by Fishers Exact test of association.

9. Correlation Between IRAE and Any Progression. [Up to 5 years]

   Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event. The correlation between IRAEs and clinical outcomes will be evaluated using logistic regression for binary endpoints and Cox regression for the time to event outcomes. Due to sample size, regression is not feasible. Instead, correlation will be assessed by Fishers Exact test of association.

10. Correlation Between IRAE and Overall Survival. [Up to 5 years]

    Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event. The correlation between IRAEs and clinical outcomes will be evaluated using logistic regression for binary endpoints and Cox regression for the time to event outcomes. Due to sample size, regression is not feasible. Instead, correlation will be assessed by Fishers Exact test of association.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Willing and able to give written informed consent

• Histologic diagnosis of adenocarcinoma of the prostate

• A PSA of > 0.2 ng/ml after 6-18 months of androgen suppression therapy, which may consist of luteinizing hormone-releasing hormone (LHRH) agonist or antagonist alone or the combination of an LHRH agonist or antagonist plus an antiandrogen, such as bicalutamide; androgen suppression therapy will continue without interruption

• Radiographic evidence of regional or distant metastasis at the time of study enrollment or at the time of diagnosis

• White blood cell (WBC) >= 2000/uL

• Absolute neutrophil count (ANC) >= 1000/uL

• Platelets >= 50 x 10^3/uL

• Hemoglobin >= 8 g/dL

• Creatinine =< 3.0 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN for patients without liver metastasis

• Bilirubin =< 3.0 x ULN, (except patients with Gilbert's syndrome, who must have a total bilirubin less than 3.0 mg/dL)

• No known active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; patients should be assessed for high risk behaviors that may result in these infections, such as intravenous drug use or multiple sexual partners; the assessment should be noted

• Eastern Cooperative Oncology Group (ECOG) =< 1

• Patients receiving any herbal product known to decrease PSA levels (i.e. saw palmetto and prostate cancer [PC]-SPES), or any immunosuppressive dose of systemic or absorbable topical corticosteroid (except prednisone up to 10 mg orally per [q] day, or its equivalent), must discontinue the agent for at least 2 weeks prior to screening; progressive disease must be documented after discontinuation of these products

• Patients receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks with stable symptoms prior to the first infusion with ipilimumab

• Total testosterone < 50 ng/ml, except in patients with prior orchiectomy, where testosterone does not need to be measured; patients must continue their LHRH agonist therapy throughout study duration

• Life expectancy >= 6 months; this must be documented

• Patients who are sexually active with a partner who could become pregnant are to use an effective form of barrier contraception, such as condoms or a partner using oral contraceptive pills; persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 8 weeks after ipilimumab is stopped

• If a patient enters the trial on androgen suppression therapy (AST) that consists of both an LHRH agonist and an oral antiandrogen, both agents should be continued throughout the study; if an antiandrogen is stopped prior to study entry, it should be stopped 4 weeks before for nilutamide and flutamide and 6 weeks before for bicalutamide to ensure that a withdrawal phenomenon does not interfere with interpretation of efficacy results

Exclusion Criteria:

• Radiation to any area of the body < 28 days prior to randomization

• Any other active malignancy with the exception of adequately treated basal or squamous cell skin cancer or superficial bladder cancer

• Autoimmune disease: patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. myasthenia gravis, Guillain-Barre syndrome); those with immune-mediated skin toxicity (i.e. toxic epidermal necrolysis, Stevens-Johnson syndrome) will also be excluded

• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea

• Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab)

• A history of prior treatment with ipilimumab or prior cluster of differentiation (CD)137 agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor or agonist

• Concomitant therapy with any of the following: interleukin (IL)-2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents (over the counter [OTC]/herbal/prescribed); immunostimulant agents, other than the study agent; other investigational therapies; or chronic use of systemic corticosteroids (greater than prednisone 10 mg orally per day, or its equivalent)

• Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (i.e., infectious) illness

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
2	OHSU Knight Cancer Institute	Portland	Oregon	United States	97239

Sponsors and Collaborators

• OHSU Knight Cancer Institute
• Bristol-Myers Squibb
• Oregon Health and Science University

Investigators

• Principal Investigator: Julie Graff, OHSU Knight Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 30, 2014

More Information

Publications

None provided.

• Responsible Party: Julie Graff, Principal Investigator, OHSU Knight Cancer Institute
• ClinicalTrials.gov Identifier: NCT01498978
• Other Study ID Numbers: IRB00005254; NCI-2011-03556; CA184059; 08-004; 5254
• First Posted: Dec 26, 2011
• Last Update Posted: Oct 14, 2020
• Last Verified: Sep 1, 2020

• Additional relevant MeSH terms: Prostatic Neoplasms; Antineoplastic Agents, Immunological; Ipilimumab; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Treatment (Ipilimumab)
Arm/Group Description	Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression then receive maintenance ipilimumab IV once every 3 months for 4 additional doses. ipilimumab: Given IV laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	10
COMPLETED	8
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Treatment (Ipilimumab)
Arm/Group Description	Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression then receive maintenance ipilimumab IV once every 3 months for 4 additional doses. ipilimumab: Given IV laboratory biomarker analysis: Correlative studies
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 50%
>=65 years	5 50%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64.5
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	10 100%
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	9 90%
More than one race	1 10%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Who Achieve an Undetectable PSA (=< 0.2 ng/ml)
Description	Undetectable PSA (prostate-specific antigen) defined as PSA ≤ 0.2 ng/mg after initiation of ipilimumab therapy. Provided with the exact 95% confidence interval. PSA response as recommended by the Prostate Cancer Clinical Trials Working Group (PCWG2) definitions. Percentage can take on values between 0% and 100%.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population -- all patients who sign the consent and are assigned to a treatment regardless of the actual drug dose the patients receive

Arm/Group Title	Treatment (Ipilimumab)
Arm/Group Description	Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression then receive maintenance ipilimumab IV once every 3 months for 4 additional doses. ipilimumab: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	10
Number (95% Confidence Interval) [percentage of patients]	0.0

2. Secondary Outcome

Title	Time to PSA Progression
Description	PSA (prostate-specific antigen) progression defined as a PSA increase of >= 25% and at least 2 ng/mL from baseline or nadir PSA achieved, confirmed by a second measurement at least three weeks later Time to PSA progression is calculated as the time from Day 1 of combination therapy to first PSA measurement of >= 25% increase and at least 2 ng/mL above the nadir and confirmed by a second measurement at least three weeks later. For subjects without a PSA decline from baseline, time to PSA progression is calculated as the time from Day 1 of combination therapy to first PSA measurement of >= 25% increase and at least 2 ng/mL increase from baseline after 12 weeks and confirmed by a second measurement at least three weeks later. Outcome is reported as median time to event determined by the Kaplan Meier method with 95% confidence interval.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population -- all patients who sign the consent and are assigned to a treatment regardless of the actual drug dose the patients receive

Arm/Group Title	Treatment (Ipilimumab)
Arm/Group Description	Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression then receive maintenance ipilimumab IV once every 3 months for 4 additional doses. ipilimumab: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	10
Median (95% Confidence Interval) [days]	525

3. Secondary Outcome

Title	Time to Progression by Any Measure
Description	Time to progression is calculated from Day 1 of combination therapy to first evidence of progression by any measure (PSA, Measurable Disease or Clinical Progression). Outcome is reported as median time to event determined by the Kaplan Meier method with 95% confidence interval.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population -- all patients who sign the consent and are assigned to a treatment regardless of the actual drug dose the patients receive

Arm/Group Title	Treatment (Ipilimumab)
Arm/Group Description	Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression then receive maintenance ipilimumab IV once every 3 months for 4 additional doses. ipilimumab: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	10
Median (95% Confidence Interval) [days]	118

4. Secondary Outcome

Title	Time to Death From Any Cause
Description	Time to death is calculated from Day 1 of combination therapy to death from any cause. Outcome is reported as median time to event determined by the Kaplan Meier method with 95% confidence interval.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population -- all patients who sign the consent and are assigned to a treatment regardless of the actual drug dose the patients receive

Arm/Group Title	Treatment (Ipilimumab)
Arm/Group Description	Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression then receive maintenance ipilimumab IV once every 3 months for 4 additional doses. ipilimumab: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	10
Median (95% Confidence Interval) [days]	1825

5. Secondary Outcome

Title	Number of Patients With IRAEs
Description	Immune-Related Adverse Events (IRAEs) are defined as an adverse event (AE) of unknown etiology associated with drug exposure and consistent with an immune phenomenon Tabulated for each treatment group and summarized according to major organ categories of the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population -- all patients who sign the consent and are assigned to a treatment regardless of the actual drug dose the patients receive

Arm/Group Title	Treatment (Ipilimumab)
Arm/Group Description	Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression then receive maintenance ipilimumab IV once every 3 months for 4 additional doses. ipilimumab: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	10
Count of Participants [Participants]	6 60%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Ipilimumab)
	Comments	Exact binomial test (two-sided). Null hypothesis: the proportion is equal to 0.5
	Type of Statistical Test	Other
	Comments	Exact binomial test (two-sided).
Statistical Test of Hypothesis	p-Value	0.754
	Comments
	Method	Exact Binomial Test
	Comments

6. Secondary Outcome

Title	Correlation Between IRAE and PSA Progression.
Description	Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event. PSA (prostate-specific antigen) Progression is defined as a PSA increase of >= 25% and at least 2 ng/mL from Baseline, or Nadir PSA Achieved, confirmed by a second measurement at least three weeks later. The correlation between IRAEs and clinical outcomes will be evaluated using logistic regression for binary endpoints and Cox regression for the time to event outcomes. Due to sample size, regression is not feasible. Instead, correlation will be assessed by Fishers Exact test of association.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population -- all patients who sign the consent and are assigned to a treatment regardless of the actual drug dose the patients receive

Arm/Group Title	Yes: IRAE	No: IRAE
Arm/Group Description	Patients that experienced an IRAE. Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event.	Patients that did not experience an IRAE. Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event.
Measure Participants	6	4
Yes: PSA Progression	5 50%	1 NaN
No: PSA progression	1 10%	3 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Ipilimumab), No: IRAE
	Comments
	Type of Statistical Test	Other
	Comments	Test of association (contingency) between the two kinds of classification.
Statistical Test of Hypothesis	p-Value	0.190
	Comments
	Method	Fisher Exact
	Comments

7. Secondary Outcome

Title	Correlation of IRAEs With Ratio of T Regulatory Cells to T Effector Cells
Description	Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event. Raw T cells data was collected, but has not been analyzed by the lab and will not be done due to constraints. No data displayed because Outcome Measure has zero total participants analyzed.
Time Frame	Up to day 1 of course 4

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population -- all patients who sign the consent and are assigned to a treatment regardless of the actual drug dose the patients receive

Arm/Group Title	Yes: IRAE	No: IRAE
Arm/Group Description	Patients that experienced an IRAE. Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event.	Patients that did not experience an IRAE. Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event.
Measure Participants	0	0

8. Secondary Outcome

Title	Correlation Between IRAEs and Immune Response
Description	Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event. Outcome not evaluated due to technical challenges collecting the data, and lack of budget and personnel to complete the analysis. No data displayed because Outcome Measure has zero total participants analyzed.
Time Frame	Up to day 1 of course 4

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population -- all patients who sign the consent and are assigned to a treatment regardless of the actual drug dose the patients receive

Arm/Group Title	Yes: IRAE	No: IRAE
Arm/Group Description	Patients that experienced an IRAE. Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event.	Patients that did not experience an IRAE. Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event.
Measure Participants	0	0

9. Secondary Outcome

Title	Correlation Between IRAE and Radiographic Progression.
Description	Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event. Radiographic progression is progression determined by scan. The correlation between IRAEs and clinical outcomes will be evaluated using logistic regression for binary endpoints and Cox regression for the time to event outcomes. Due to sample size, regression is not feasible. Instead, correlation will be assessed by Fishers Exact test of association.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population -- all patients who sign the consent and are assigned to a treatment regardless of the actual drug dose the patients receive

Arm/Group Title	Yes: IRAE	No: IRAE
Arm/Group Description	Patients that experienced an IRAE. Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event.	Patients that did not experience an IRAE. Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event.
Measure Participants	6	4
Yes: Radiographic progression	1 10%	2 NaN
No: Radiographic progression	5 50%	2 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Ipilimumab), No: IRAE
	Comments
	Type of Statistical Test	Other
	Comments	Test of association (contingency) between the two kinds of classification.
Statistical Test of Hypothesis	p-Value	0.500
	Comments
	Method	Fisher Exact
	Comments

10. Secondary Outcome

Title	Correlation Between IRAE and Any Progression.
Description	Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event. The correlation between IRAEs and clinical outcomes will be evaluated using logistic regression for binary endpoints and Cox regression for the time to event outcomes. Due to sample size, regression is not feasible. Instead, correlation will be assessed by Fishers Exact test of association.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population -- all patients who sign the consent and are assigned to a treatment regardless of the actual drug dose the patients receive

Arm/Group Title	Yes: IRAE	No: IRAE
Arm/Group Description	Patients that experienced an IRAE. Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event.	Patients that did not experience an IRAE. Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event.
Measure Participants	6	4
Yes: Any progression	5 50%	3 NaN
No: Any progression	1 10%	1 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Ipilimumab), No: IRAE
	Comments
	Type of Statistical Test	Other
	Comments	Test of association (contingency) between the two kinds of classification.
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

11. Secondary Outcome

Title	Correlation Between IRAE and Overall Survival.
Description	Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event. The correlation between IRAEs and clinical outcomes will be evaluated using logistic regression for binary endpoints and Cox regression for the time to event outcomes. Due to sample size, regression is not feasible. Instead, correlation will be assessed by Fishers Exact test of association.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population -- all patients who sign the consent and are assigned to a treatment regardless of the actual drug dose the patients receive

Arm/Group Title	Yes: IRAE	No: IRAE
Arm/Group Description	Patients that experienced an IRAE. Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event.	Patients that did not experience an IRAE. Immune related adverse event (IRAE) is defined as any adverse event associated with drug exposure and consistent with an immune-mediated event.
Measure Participants	6	4
Yes: Deceased	2 20%	3 NaN
No:Deceased	4 40%	1 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Ipilimumab), No: IRAE
	Comments
	Type of Statistical Test	Other
	Comments	Test of association (contingency) between the two kinds of classification.
Statistical Test of Hypothesis	p-Value	0.524
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	Adverse Events were collected from the start of Ipilimumab therapy until off study for progression, adverse event or other reason, an average of one year.
Adverse Event Reporting Description	Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Arm/Group Title	Treatment (Ipilimumab)
Arm/Group Description	Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression then receive maintenance ipilimumab IV once every 3 months for 4 additional doses. ipilimumab: Given IV laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Treatment (Ipilimumab)
	Affected / at Risk (%)	# Events
Total	2/10 (20%)
Serious Adverse Events
	Treatment (Ipilimumab)
	Affected / at Risk (%)	# Events
Total	1/10 (10%)
Gastrointestinal disorders
Diarrhea	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Ipilimumab)
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Endocrine disorders
Adrenal insufficiency	1/10 (10%)	1
Gastrointestinal disorders
Diarrhea	6/10 (60%)	11
Vomiting	1/10 (10%)	1
Colitis	1/10 (10%)	1
Nausea	2/10 (20%)	2
Bloating	1/10 (10%)	1
General disorders
Fatigue	4/10 (40%)	4
Fever	3/10 (30%)	3
Flu like symptoms	1/10 (10%)	1
Chills	1/10 (10%)	1
Malaise	1/10 (10%)	1
Investigations
Creatinine increased	1/10 (10%)	1
Aspartate aminotransferase	1/10 (10%)	2
Alanine aminotransferase	1/10 (10%)	2
Alkaline phosphatase	1/10 (10%)	1
Metabolism and nutrition disorders
Anorexia	1/10 (10%)	1
Hyponatremia	1/10 (10%)	1
Hypokalemia	1/10 (10%)	1
Musculoskeletal and connective tissue disorders
Myalgia	3/10 (30%)	5
Musculoskeletal and connective tissue disorder - Other	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Pruritus	4/10 (40%)	4
Skin and subcutaneous tissue disorders - Other	4/10 (40%)	4
Dry Skin	1/10 (10%)	1
Rash maculo-papular	2/10 (20%)	2
Vascular disorders
Hypotension	2/10 (20%)	2

Limitations/Caveats

[Not Specified]

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.