Trial Outcomes & Findings for Ipilimumab in Combination With Androgen Suppression Therapy in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer (NCT NCT01498978)

NCT ID: NCT01498978

Last Updated: 2020-10-14

Results Overview

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%.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 10 participants
• Primary outcome timeframe: Up to 5 years
• Results posted on: 2020-10-14

Participant Flow

Participant milestones

Measure	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. ipilimumab: Given IV laboratory biomarker analysis: Correlative studies
Overall Study STARTED	10
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Treatment (Ipilimumab) n=10 Participants 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
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants
Age, Continuous	64.5 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 5 years

Population: 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

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%.

Outcome measures

Measure	Treatment (Ipilimumab) n=10 Participants 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	No: IRAE 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.
Percentage of Patients Who Achieve an Undetectable PSA (=< 0.2 ng/ml)	0.0 percentage of patients Interval 0.0 to 0.0	—

SECONDARY outcome

Timeframe: Up to 5 years

Population: 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

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.

Outcome measures

Measure	Treatment (Ipilimumab) n=10 Participants 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	No: IRAE 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.
Time to PSA Progression	525 days Interval 77.0 to Upper limit not able to be estimated.	—

SECONDARY outcome

Timeframe: Up to 5 years

Population: 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

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.

Outcome measures

Measure	Treatment (Ipilimumab) n=10 Participants 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	No: IRAE 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.
Time to Progression by Any Measure	118 days Interval 63.0 to 532.0	—

SECONDARY outcome

Timeframe: Up to 5 years

Population: 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

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.

Outcome measures

Measure	Treatment (Ipilimumab) n=10 Participants 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	No: IRAE 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.
Time to Death From Any Cause	1825 days Interval 470.0 to Upper limit not able to be estimated.	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: 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

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.

Outcome measures

Measure	Treatment (Ipilimumab) n=10 Participants 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	No: IRAE 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.
Number of Patients With IRAEs	6 Participants	—

SECONDARY outcome

Timeframe: Up to 5 years

Population: 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

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.

Outcome measures

Measure	Treatment (Ipilimumab) n=6 Participants 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	No: IRAE n=4 Participants 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.
Correlation Between IRAE and PSA Progression. Yes: PSA Progression	5 Participants	1 Participants
Correlation Between IRAE and PSA Progression. No: PSA progression	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to day 1 of course 4

Population: 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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to day 1 of course 4

Population: 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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years

Population: 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

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.

Outcome measures

Measure	Treatment (Ipilimumab) n=6 Participants 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	No: IRAE n=4 Participants 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.
Correlation Between IRAE and Radiographic Progression. Yes: Radiographic progression	1 Participants	2 Participants
Correlation Between IRAE and Radiographic Progression. No: Radiographic progression	5 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 5 years

Population: 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

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.

Outcome measures

Measure	Treatment (Ipilimumab) n=6 Participants 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	No: IRAE n=4 Participants 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.
Correlation Between IRAE and Any Progression. Yes: Any progression	5 Participants	3 Participants
Correlation Between IRAE and Any Progression. No: Any progression	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 5 years

Population: 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

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.

Outcome measures

Measure	Treatment (Ipilimumab) n=6 Participants 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	No: IRAE n=4 Participants 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.
Correlation Between IRAE and Overall Survival. Yes: Deceased	2 Participants	3 Participants
Correlation Between IRAE and Overall Survival. No:Deceased	4 Participants	1 Participants

Adverse Events

Treatment (Ipilimumab)

Serious events: 1 serious events

Other events: 10 other events

Deaths: 2 deaths

Serious adverse events

Measure

Treatment (Ipilimumab) n=10 participants at risk 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

Gastrointestinal disorders Diarrhea

10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.

Other adverse events

Measure	Treatment (Ipilimumab) n=10 participants at risk 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
Skin and subcutaneous tissue disorders Pruritus	40.0% 4/10 • Number of events 4 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Gastrointestinal disorders Diarrhea	60.0% 6/10 • Number of events 11 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	40.0% 4/10 • Number of events 4 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
General disorders Fatigue	40.0% 4/10 • Number of events 4 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
General disorders Fever	30.0% 3/10 • Number of events 3 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Musculoskeletal and connective tissue disorders Myalgia	30.0% 3/10 • Number of events 5 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Skin and subcutaneous tissue disorders Dry Skin	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Vascular disorders Hypotension	20.0% 2/10 • Number of events 2 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Gastrointestinal disorders Vomiting	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Investigations Creatinine increased	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
General disorders Flu like symptoms	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Investigations Aspartate aminotransferase	10.0% 1/10 • Number of events 2 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Investigations Alanine aminotransferase	10.0% 1/10 • Number of events 2 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Investigations Alkaline phosphatase	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Gastrointestinal disorders Colitis	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Endocrine disorders Adrenal insufficiency	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Gastrointestinal disorders Nausea	20.0% 2/10 • Number of events 2 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
General disorders Chills	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Metabolism and nutrition disorders Anorexia	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Gastrointestinal disorders Bloating	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
General disorders Malaise	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Metabolism and nutrition disorders Hyponatremia	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Metabolism and nutrition disorders Hypokalemia	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	10.0% 1/10 • Number of events 1 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.
Skin and subcutaneous tissue disorders Rash maculo-papular	20.0% 2/10 • Number of events 2 • 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. Only Adverse Events that are considered possibly related or related to the study procedures or study drug are reported.

Additional Information

Kristi Eilers

OHSU Knight Cancer Institute

Phone: 503-494-2897

Email: eilersk@ohsu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place