Trial Outcomes & Findings for Nivolumab With DC Vaccines for Recurrent Brain Tumors (NCT NCT02529072)
NCT ID: NCT02529072
Last Updated: 2020-03-26
Results Overview
The percentage of patients who experience unacceptable toxicity during combination treatment by arm is tabulated. Unacceptable toxicity is defined as any grade 3, 4, or 5 adverse event that is possibly, probably, or definitely related to either nivolumab or DC vaccination treatment during concurrent treatment, or any Grade 2 drug-related uveitis or eye pain or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within the re-treatment period OR requires systemic treatment. In addition, any complication following resection (ex. excessive intracranial bleeding, delays in wound healing) that are prolonged longer than 4-6 weeks post-surgery will be considered an unacceptable toxicity.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
6 participants
Primary outcome timeframe
12 months
Results posted on
2020-03-26
Participant Flow
Participant milestones
| Measure |
Group I
Patients will receive nivolumab 3 mg/kg IV every 2 weeks for 8 weeks followed by surgery. Following resection, nivolumab and DC vaccine will be administered every 2 weeks (± 1) for a total of 3 vaccines, followed by biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
Group II
Patients will initially receive the fourth cycle of nivolumab then receive nivolumab 3 mg/kg IV and DC vaccine every 2 weeks for a total of 3 vaccines, and then surgery. Subsequent to surgery, the patient will resume biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
|
Overall Study
COMPLETED
|
3
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Nivolumab With DC Vaccines for Recurrent Brain Tumors
Baseline characteristics by cohort
| Measure |
Group I
n=3 Participants
Patients will receive nivolumab 3 mg/kg IV every 2 weeks for 8 weeks followed by surgery. Following resection, nivolumab and DC vaccine will be administered every 2 weeks (± 1) for a total of 3 vaccines, followed by biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
Group II
n=3 Participants
Patients will initially receive the fourth cycle of nivolumab then receive nivolumab 3 mg/kg IV and DC vaccine every 2 weeks for a total of 3 vaccines, and then surgery. Subsequent to surgery, the patient will resume biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
Total
n=6 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52.9 years
STANDARD_DEVIATION 6.6 • n=5 Participants
|
61.2 years
STANDARD_DEVIATION 1.8 • n=7 Participants
|
57.1 years
STANDARD_DEVIATION 6.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: All randomized patients are included in this analysis
The percentage of patients who experience unacceptable toxicity during combination treatment by arm is tabulated. Unacceptable toxicity is defined as any grade 3, 4, or 5 adverse event that is possibly, probably, or definitely related to either nivolumab or DC vaccination treatment during concurrent treatment, or any Grade 2 drug-related uveitis or eye pain or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within the re-treatment period OR requires systemic treatment. In addition, any complication following resection (ex. excessive intracranial bleeding, delays in wound healing) that are prolonged longer than 4-6 weeks post-surgery will be considered an unacceptable toxicity.
Outcome measures
| Measure |
Group I
n=3 Participants
Patients will receive nivolumab 3 mg/kg IV every 2 weeks for 8 weeks followed by surgery. Following resection, nivolumab and DC vaccine will be administered every 2 weeks (± 1) for a total of 3 vaccines, followed by biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
Group II
n=3 Participants
Patients will initially receive the fourth cycle of nivolumab then receive nivolumab 3 mg/kg IV and DC vaccine every 2 weeks for a total of 3 vaccines, and then surgery. Subsequent to surgery, the patient will resume biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
|---|---|---|
|
The Safety of Administering DC Vaccines With Nivolumab
|
0 Percentage of patients
|
0 Percentage of patients
|
SECONDARY outcome
Timeframe: approximately 4 years from study initiationPopulation: All randomized patients are included in this analysis
Survival is defined as the time between first initiation of nivolumab and death, or last follow-up if the patient remains alive. The Kaplan-Meier estimator will be used to describe the overall survival (OS) experience of all patients. Median OS is presented. Patients who are not able to tolerate nivolumab and are removed from the study will not be included in these analyses. Patients for whom DC vaccines cannot be manufactured will not be included in the survival analyses.
Outcome measures
| Measure |
Group I
n=3 Participants
Patients will receive nivolumab 3 mg/kg IV every 2 weeks for 8 weeks followed by surgery. Following resection, nivolumab and DC vaccine will be administered every 2 weeks (± 1) for a total of 3 vaccines, followed by biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
Group II
n=3 Participants
Patients will initially receive the fourth cycle of nivolumab then receive nivolumab 3 mg/kg IV and DC vaccine every 2 weeks for a total of 3 vaccines, and then surgery. Subsequent to surgery, the patient will resume biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
|---|---|---|
|
Overall Survival
|
8.0 months
Interval 5.7 to 8.3
|
15.3 months
Interval 4.73 to
The upper limit is not estimable due an insufficient number of patients and events
|
SECONDARY outcome
Timeframe: 6 to 48 months from study initiationPopulation: All randomized patients are included in this analysis
PFS is defined as the time between treatment initiation and initial progression or death, or date of last follow-up if the patient remains alive without disease progression. The Kaplan-Meier estimator will be used to describe the PFS experience of all patients. Median PFS is presented. Patients who are not able to tolerate nivolumab and are removed from the study will not be included in these analyses. Patients for whom DC vaccines cannot be manufactured will not be included in the survival analyses. Tumor assessment will be made using Response Assessment in Neuro-Oncology (RANO) criteria, which defines progressive disease as an increase by at least 25% in the sum of the products of perpendicular diameters from the baseline scan, a significant increase in T2/FLAIR non-enhancing lesions, or clinical decline
Outcome measures
| Measure |
Group I
n=3 Participants
Patients will receive nivolumab 3 mg/kg IV every 2 weeks for 8 weeks followed by surgery. Following resection, nivolumab and DC vaccine will be administered every 2 weeks (± 1) for a total of 3 vaccines, followed by biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
Group II
n=3 Participants
Patients will initially receive the fourth cycle of nivolumab then receive nivolumab 3 mg/kg IV and DC vaccine every 2 weeks for a total of 3 vaccines, and then surgery. Subsequent to surgery, the patient will resume biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
|---|---|---|
|
Progression Free Survival (PFS)
|
4.3 months
Interval 2.1 to 5.3
|
6.3 months
Interval 4.7 to 10.7
|
Adverse Events
Group I
Serious events: 1 serious events
Other events: 3 other events
Deaths: 3 deaths
Group II
Serious events: 2 serious events
Other events: 3 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Group I
n=3 participants at risk
Patients will receive nivolumab 3 mg/kg IV every 2 weeks for 8 weeks followed by surgery. Following resection, nivolumab and DC vaccine will be administered every 2 weeks (± 1) for a total of 3 vaccines, followed by biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
Group II
n=3 participants at risk
Patients will initially receive the fourth cycle of nivolumab then receive nivolumab 3 mg/kg IV and DC vaccine every 2 weeks for a total of 3 vaccines, and then surgery. Subsequent to surgery, the patient will resume biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
|---|---|---|
|
Infections and infestations
Meningitis
|
0.00%
0/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Infections and infestations
Wound infection
|
0.00%
0/3 • 12 months
|
66.7%
2/3 • 12 months
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other, Specify: L EAR LACERATION
|
0.00%
0/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Nervous system disorders
Hydrocephalus
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Vascular disorders
Thromboembolic event
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
Other adverse events
| Measure |
Group I
n=3 participants at risk
Patients will receive nivolumab 3 mg/kg IV every 2 weeks for 8 weeks followed by surgery. Following resection, nivolumab and DC vaccine will be administered every 2 weeks (± 1) for a total of 3 vaccines, followed by biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
Group II
n=3 participants at risk
Patients will initially receive the fourth cycle of nivolumab then receive nivolumab 3 mg/kg IV and DC vaccine every 2 weeks for a total of 3 vaccines, and then surgery. Subsequent to surgery, the patient will resume biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
66.7%
2/3 • 12 months
|
100.0%
3/3 • 12 months
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Endocrine disorders
Endocrine disorders - Other, Specify: ELEVATED TSH; POSSIBLY RELATED TO NIVO
|
0.00%
0/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Eye disorders
Blurred vision
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • 12 months
|
66.7%
2/3 • 12 months
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Gastrointestinal disorders
Fecal incontinence
|
0.00%
0/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, Specify: POLYDIPSIA
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Gastrointestinal disorders
Nausea
|
33.3%
1/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
General disorders
Edema face
|
0.00%
0/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
General disorders
Edema limbs
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
General disorders
Fatigue
|
66.7%
2/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
General disorders
Gait disturbance
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
General disorders
Pain
|
33.3%
1/3 • 12 months
|
66.7%
2/3 • 12 months
|
|
Infections and infestations
Infections and infestations - Other, Specify: HEAD INCISION IRRITATION
|
0.00%
0/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Infections and infestations
Infections and infestations - Other, Specify: SMALL CUT ON L HAND
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Infections and infestations
Infections and infestations - Other, Specify: YEAST INFECTION
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Infections and infestations
Mucosal infection
|
33.3%
1/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Infections and infestations
Upper respiratory infection
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/3 • 12 months
|
66.7%
2/3 • 12 months
|
|
Investigations
Activated partial thromboplastin time prolonged
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Investigations
Lymphocyte count decreased
|
66.7%
2/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Investigations
Platelet count decreased
|
33.3%
1/3 • 12 months
|
66.7%
2/3 • 12 months
|
|
Metabolism and nutrition disorders
Anorexia
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Metabolism and nutrition disorders
Dehydration
|
33.3%
1/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
100.0%
3/3 • 12 months
|
100.0%
3/3 • 12 months
|
|
Metabolism and nutrition disorders
Hypernatremia
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
33.3%
1/3 • 12 months
|
66.7%
2/3 • 12 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
66.7%
2/3 • 12 months
|
66.7%
2/3 • 12 months
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
33.3%
1/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
33.3%
1/3 • 12 months
|
66.7%
2/3 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness left-sided
|
0.00%
0/3 • 12 months
|
66.7%
2/3 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders - Other, Specify: STEROID MYOPATHY
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Specify: SWOLLEN NECK
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Nervous system disorders
Cerebrospinal fluid leakage
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Nervous system disorders
Dysphasia
|
66.7%
2/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Nervous system disorders
Headache
|
33.3%
1/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Nervous system disorders
Memory impairment
|
33.3%
1/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Nervous system disorders
Nervous system disorders - Other, Specify: FACIAL DROOP
|
0.00%
0/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Nervous system disorders
Nervous system disorders - Other, Specify: WEAKNESS IN R HAND
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Nervous system disorders
Paresthesia
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Nervous system disorders
Seizure
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Nervous system disorders
Tremor
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Psychiatric disorders
Confusion
|
33.3%
1/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Psychiatric disorders
Depression
|
0.00%
0/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Psychiatric disorders
Insomnia
|
33.3%
1/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Renal and urinary disorders
Urinary frequency
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Renal and urinary disorders
Urinary incontinence
|
33.3%
1/3 • 12 months
|
33.3%
1/3 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, Specify: COLD
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Specify: CLAMMY AND COOL SKIN
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
|
Vascular disorders
Thromboembolic event
|
33.3%
1/3 • 12 months
|
0.00%
0/3 • 12 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place