Trial Outcomes & Findings for Nivolumab With or Without Ipilimumab in Treating Patients With Resectable Liver Cancer (NCT NCT03222076)
NCT ID: NCT03222076
Last Updated: 2023-07-10
Results Overview
The frequency of adverse events, serious adverse events (grade ≥3), and laboratory abnormalities. Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Safety will be recorded through the incidence of adverse events, serious adverse events and specific laboratory abnormalities (worst grade) in each treatment arm.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
30 participants
Primary outcome timeframe
Up to 5 years
Results posted on
2023-07-10
Participant Flow
3 excluded: 1 did not meet inclusion criteria; 2 declined to participate The study was amended in June 2019 to remove/exclude the enrollment of Arm C .
Participant milestones
| Measure |
Arm A: Nivolumab
Nivolumab at 240 mg IV every 2 weeks for 3 doses followed by liver imaging and hepatic resection on day 1 of week 7, followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks in the adjuvant setting until disease progression or for 2 years, whichever is sooner
Nivolumab: Given IV
|
Arm B: Nivolumab Plus Ipilimumab
Nivolumab 240 mg IV every 2 weeks for 3 doses plus ipilimumab 1 mg/kg IV on day 1 of therapy (3 doses of nivolumab, 1 dose of ipilimumab) followed by hepatic resection followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks plus ipilimumab 1 mg/kg IV every 6 weeks to 4 doses in the adjuvant settingIpilimumab: Given IV
Nivolumab: Given IV Ipilimumab: Given IV
|
Arm C: Nivolumab Plus Ipilimumab
Nivolumab 240 mg IV every 2 weeks for 3 doses plus ipilimumab 1 mg/kg IV on day 1 of therapy (3 doses of nivolumab, 1 dose of ipilimumab; 6 weeks) in Unresectable patients followed by post-treatment biopsy
|
|---|---|---|---|
|
Overall Study
STARTED
|
13
|
14
|
0
|
|
Overall Study
COMPLETED
|
13
|
14
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Nivolumab With or Without Ipilimumab in Treating Patients With Resectable Liver Cancer
Baseline characteristics by cohort
| Measure |
Arm A: Nivolumab
n=13 Participants
Nivolumab at 240 mg IV every 2 weeks for 3 doses followed by liver imaging and hepatic resection on day 1 of week 7, followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks in the adjuvant setting until disease progression or for 2 years, whichever is sooner
|
Arm B: Nivolumab Plus Ipilimumab
n=14 Participants
Nivolumab 240 mg IV every 2 weeks for 3 doses plus ipilimumab 1 mg/kg IV on day 1 of therapy (3 doses of nivolumab, 1 dose of ipilimumab) followed by hepatic resection followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks plus ipilimumab 1 mg/kg IV every 6 weeks to 4 doses in the adjuvant setting
|
Arm C: Nivolumab Plus Ipilimumab
Nivolumab 240 mg IV every 2 weeks for 3 doses plus ipilimumab 1 mg/kg IV on day 1 of therapy (3 doses of nivolumab, 1 dose of ipilimumab; 6 weeks) in Unresectable patients followed by post-treatment biopsy
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
64 years
n=5 Participants
|
62 years
n=7 Participants
|
—
|
64 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
—
|
8 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
—
|
19 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
—
|
7 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
—
|
7 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
—
|
13 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
13 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
—
|
27 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to 5 yearsPopulation: Cohort C that was discontinued due to non-accrual.
The frequency of adverse events, serious adverse events (grade ≥3), and laboratory abnormalities. Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Safety will be recorded through the incidence of adverse events, serious adverse events and specific laboratory abnormalities (worst grade) in each treatment arm.
Outcome measures
| Measure |
Arm A: Nivolumab
n=13 Participants
Nivolumab at 240 mg IV every 2 weeks for 3 doses followed by liver imaging and hepatic resection on day 1 of week 7, followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks in the adjuvant setting until disease progression or for 2 years, whichever is sooner
|
Arm B: Nivolumab Plus Ipilimumab
n=14 Participants
Nivolumab 240 mg IV every 2 weeks for 3 doses plus ipilimumab 1 mg/kg IV on day 1 of therapy (3 doses of nivolumab, 1 dose of ipilimumab) followed by hepatic resection followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks plus ipilimumab 1 mg/kg IV every 6 weeks to 4 doses in the adjuvant setting
|
Arm C: Nivolumab Plus Ipilimumab
Nivolumab 240 mg IV every 2 weeks for 3 doses plus ipilimumab 1 mg/kg IV on day 1 of therapy (3 doses of nivolumab, 1 dose of ipilimumab; 6 weeks) in Unresectable patients followed by post-treatment biopsy
|
|---|---|---|---|
|
Safety and Tolerability of Presurgical Nivolumab With or Without Ipilimumab, Defined as the Number of Participants With of Adverse Events.
|
13 Participants
|
14 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: After 6 weeks of therapy, up to 5 yearsPopulation: Cohort C that was discontinued due to non-accrual.
Overall response rate, defined as the proportion of patients with a complete response or partial response after 6 weeks of therapy by RECIST 1.1 criteria divided by the number of randomly assigned patients.
Outcome measures
| Measure |
Arm A: Nivolumab
n=13 Participants
Nivolumab at 240 mg IV every 2 weeks for 3 doses followed by liver imaging and hepatic resection on day 1 of week 7, followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks in the adjuvant setting until disease progression or for 2 years, whichever is sooner
|
Arm B: Nivolumab Plus Ipilimumab
n=14 Participants
Nivolumab 240 mg IV every 2 weeks for 3 doses plus ipilimumab 1 mg/kg IV on day 1 of therapy (3 doses of nivolumab, 1 dose of ipilimumab) followed by hepatic resection followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks plus ipilimumab 1 mg/kg IV every 6 weeks to 4 doses in the adjuvant setting
|
Arm C: Nivolumab Plus Ipilimumab
Nivolumab 240 mg IV every 2 weeks for 3 doses plus ipilimumab 1 mg/kg IV on day 1 of therapy (3 doses of nivolumab, 1 dose of ipilimumab; 6 weeks) in Unresectable patients followed by post-treatment biopsy
|
|---|---|---|---|
|
Objective Response Rate
|
3 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: 2 of the patients (1 in the Nivolumab arm and 1 in the Nivolumab + Ipilimumab arm) was not included in the analysis of PFS because their surgical cancellations were unrelated to progressive disease. Upper limit of 95% Confidence Interval is not estimable due to insufficient number of participants and number of events.
Time to progression defined as the time from the start of the study drug to the first documented tumor progression or recurrence of the tumor as determined by the investigator by RECIST 1.1 or immune-related response criteria.
Outcome measures
| Measure |
Arm A: Nivolumab
n=12 Participants
Nivolumab at 240 mg IV every 2 weeks for 3 doses followed by liver imaging and hepatic resection on day 1 of week 7, followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks in the adjuvant setting until disease progression or for 2 years, whichever is sooner
|
Arm B: Nivolumab Plus Ipilimumab
n=13 Participants
Nivolumab 240 mg IV every 2 weeks for 3 doses plus ipilimumab 1 mg/kg IV on day 1 of therapy (3 doses of nivolumab, 1 dose of ipilimumab) followed by hepatic resection followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks plus ipilimumab 1 mg/kg IV every 6 weeks to 4 doses in the adjuvant setting
|
Arm C: Nivolumab Plus Ipilimumab
Nivolumab 240 mg IV every 2 weeks for 3 doses plus ipilimumab 1 mg/kg IV on day 1 of therapy (3 doses of nivolumab, 1 dose of ipilimumab; 6 weeks) in Unresectable patients followed by post-treatment biopsy
|
|---|---|---|---|
|
Time to Progression
|
9.4 months
Interval 1.47 to
2 of the patients (1 in the Nivolumab arm and 1 in the Nivolumab + Ipilimumab arm) was not included in the analysis of PFS because their surgical cancellations were unrelated to progressive disease.
|
19.53 months
Interval 2.33 to
2 of the patients (1 in the Nivolumab arm and 1 in the Nivolumab + Ipilimumab arm) was not included in the analysis of PFS because their surgical cancellations were unrelated to progressive disease.
|
—
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: 2 of the patients (1 in the Nivolumab arm and 1 in the Nivolumab + Ipilimumab arm) was not included in the analysis of PFS because their surgical cancellations were unrelated to progressive disease. Upper limit of 95% Confidence Interval is not estimable due to insufficient number of participants and number of events.
Progression free survival, defined as the time from the start of treatment to the date of progessive disease, recurrence, or death, whichever occurred first. The Kaplan-Meier method will be used to estimate probability of PFS for each treatment arm.
Outcome measures
| Measure |
Arm A: Nivolumab
n=12 Participants
Nivolumab at 240 mg IV every 2 weeks for 3 doses followed by liver imaging and hepatic resection on day 1 of week 7, followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks in the adjuvant setting until disease progression or for 2 years, whichever is sooner
|
Arm B: Nivolumab Plus Ipilimumab
n=13 Participants
Nivolumab 240 mg IV every 2 weeks for 3 doses plus ipilimumab 1 mg/kg IV on day 1 of therapy (3 doses of nivolumab, 1 dose of ipilimumab) followed by hepatic resection followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks plus ipilimumab 1 mg/kg IV every 6 weeks to 4 doses in the adjuvant setting
|
Arm C: Nivolumab Plus Ipilimumab
Nivolumab 240 mg IV every 2 weeks for 3 doses plus ipilimumab 1 mg/kg IV on day 1 of therapy (3 doses of nivolumab, 1 dose of ipilimumab; 6 weeks) in Unresectable patients followed by post-treatment biopsy
|
|---|---|---|---|
|
Progression Free Survival (PFS)
|
9.4 months
Interval 1.47 to
2 of the patients (1 in the Nivolumab arm and 1 in the Nivolumab + Ipilimumab arm) was not included in the analysis of PFS because their surgical cancellations were unrelated to progressive disease.
|
19.53 months
Interval 2.33 to
2 of the patients (1 in the Nivolumab arm and 1 in the Nivolumab + Ipilimumab arm) was not included in the analysis of PFS because their surgical cancellations were unrelated to progressive disease.
|
—
|
Adverse Events
Nivolumab
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Nivolumab Plus Ipilimumab
Serious events: 0 serious events
Other events: 12 other events
Deaths: 4 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Nivolumab
n=13 participants at risk
Nivolumab at 240 mg IV every 2 weeks for 3 doses followed by liver imaging and hepatic resection on day 1 of week 7, followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks in the adjuvant setting until disease progression or for 2 years, whichever is sooner
Nivolumab: Given IV
|
Nivolumab Plus Ipilimumab
n=14 participants at risk
Nivolumab 240 mg IV every 2 weeks for 3 doses plus ipilimumab 1 mg/kg IV on day 1 of therapy (3 doses of nivolumab, 1 dose of ipilimumab) followed by hepatic resection followed (after 4 weeks from surgery) by nivolumab 480 mg IV every 4 weeks plus ipilimumab 1 mg/kg IV every 6 weeks to 4 doses in the adjuvant settingIpilimumab: Given IV
Nivolumab: Given IV Ipilimumab: Given IV
|
|---|---|---|
|
Investigations
Anaemia
|
15.4%
2/13 • Number of events 2 • Overall Study (Up to 5 years)
|
21.4%
3/14 • Number of events 3 • Overall Study (Up to 5 years)
|
|
Investigations
Increased alanine aminotransferase
|
23.1%
3/13 • Number of events 3 • Overall Study (Up to 5 years)
|
50.0%
7/14 • Number of events 7 • Overall Study (Up to 5 years)
|
|
Investigations
Increased aspartate aminotransferase
|
23.1%
3/13 • Number of events 3 • Overall Study (Up to 5 years)
|
50.0%
7/14 • Number of events 7 • Overall Study (Up to 5 years)
|
|
Investigations
Decreased platelet count
|
15.4%
2/13 • Number of events 2 • Overall Study (Up to 5 years)
|
7.1%
1/14 • Number of events 1 • Overall Study (Up to 5 years)
|
|
Investigations
Lipase increased
|
15.4%
2/13 • Number of events 2 • Overall Study (Up to 5 years)
|
7.1%
1/14 • Number of events 1 • Overall Study (Up to 5 years)
|
|
General disorders
Fatigue
|
7.7%
1/13 • Number of events 1 • Overall Study (Up to 5 years)
|
42.9%
6/14 • Number of events 6 • Overall Study (Up to 5 years)
|
|
Endocrine disorders
Hypothyroidism
|
15.4%
2/13 • Number of events 2 • Overall Study (Up to 5 years)
|
14.3%
2/14 • Number of events 2 • Overall Study (Up to 5 years)
|
|
Gastrointestinal disorders
Nausea
|
23.1%
3/13 • Number of events 3 • Overall Study (Up to 5 years)
|
21.4%
3/14 • Number of events 3 • Overall Study (Up to 5 years)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
15.4%
2/13 • Number of events 2 • Overall Study (Up to 5 years)
|
7.1%
1/14 • Number of events 1 • Overall Study (Up to 5 years)
|
|
Skin and subcutaneous tissue disorders
Maculopapular rash
|
30.8%
4/13 • Number of events 4 • Overall Study (Up to 5 years)
|
21.4%
3/14 • Number of events 3 • Overall Study (Up to 5 years)
|
|
Gastrointestinal disorders
Constipation
|
15.4%
2/13 • Number of events 2 • Overall Study (Up to 5 years)
|
7.1%
1/14 • Number of events 1 • Overall Study (Up to 5 years)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place