Trial Outcomes & Findings for Ipilimumab Induction in Patients With Melanoma Brain Metastases Receiving Stereotactic Radiosurgery (NCT NCT02097732)

NCT ID: NCT02097732

Last Updated: 2021-05-12

Results Overview

The number of patients in each arm who are free from progression in the index (radiated) lesions in the brain at 6 months. Immune related response criteria was used to assess response to treatment. Immune-related Progressive Disease (irPD) in this trial is defined as an increase in tumor burden ≥25% relative to nadir (minimum recorded tumor burden), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

6 months

Results posted on

2021-05-12

Participant Flow

Participant milestones

Participant milestones
Measure	B: No Induction Participants will undergo stereotactic radiosurgery (SRS) followed 2-3 weeks later by ipilimumab, which is given once every 3 weeks for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.	A: Induction Patients will receive 2 doses of ipilimumab, which is given once every 3 weeks, prior to stereotactic radiosurgery (SRS), followed by 2 more doses of ipilimumab, for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.
Overall Study STARTED	1	3
Overall Study COMPLETED	1	3
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ipilimumab Induction in Patients With Melanoma Brain Metastases Receiving Stereotactic Radiosurgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	B: No Induction n=1 Participants Participants will undergo stereotactic radiosurgery (SRS) followed 2-3 weeks later by ipilimumab, which is given once every 3 weeks for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.	A: Induction n=3 Participants Patients will receive 2 doses of ipilimumab, which is given once every 3 weeks, prior to stereotactic radiosurgery (SRS), followed by 2 more doses of ipilimumab, for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.	Total n=4 Participants Total of all reporting groups
Age, Continuous	69 years n=5 Participants	55 years n=7 Participants	58 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	B: No Induction n=1 Participants Participants will undergo stereotactic radiosurgery (SRS) followed 2-3 weeks later by ipilimumab, which is given once every 3 weeks for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.	A: Induction n=3 Participants Patients will receive 2 doses of ipilimumab, which is given once every 3 weeks, prior to stereotactic radiosurgery (SRS), followed by 2 more doses of ipilimumab, for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.
Local Control Rate	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 5 years

Number of participants alive at 5 years after enrollment.

Outcome measures

Outcome measures
Measure	B: No Induction n=1 Participants Participants will undergo stereotactic radiosurgery (SRS) followed 2-3 weeks later by ipilimumab, which is given once every 3 weeks for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.	A: Induction n=3 Participants Patients will receive 2 doses of ipilimumab, which is given once every 3 weeks, prior to stereotactic radiosurgery (SRS), followed by 2 more doses of ipilimumab, for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.
Overall Survival Rate	1 participants	2 participants

SECONDARY outcome

Timeframe: 6 months

The proportion of patients in each arm who are free from progression in the index (radiated) lesions and free from new brain metastases at 6 months.

Outcome measures

Outcome measures
Measure	B: No Induction n=1 Participants Participants will undergo stereotactic radiosurgery (SRS) followed 2-3 weeks later by ipilimumab, which is given once every 3 weeks for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.	A: Induction n=3 Participants Patients will receive 2 doses of ipilimumab, which is given once every 3 weeks, prior to stereotactic radiosurgery (SRS), followed by 2 more doses of ipilimumab, for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.
Regional (Intracranial) Control Rate	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Response of treated (irradiated) brain metastases to combination therapy with ipilimumab and stereotactic radiosurgery using immune-related response criteria.

Outcome measures

Outcome measures
Measure	B: No Induction n=1 Participants Participants will undergo stereotactic radiosurgery (SRS) followed 2-3 weeks later by ipilimumab, which is given once every 3 weeks for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.	A: Induction n=3 Participants Patients will receive 2 doses of ipilimumab, which is given once every 3 weeks, prior to stereotactic radiosurgery (SRS), followed by 2 more doses of ipilimumab, for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.
Intracranial Response Rate	1 Participants	3 Participants

SECONDARY outcome

Timeframe: From date of enrollment to up to 2 years

Population: Of the 4 patients, 2 patients remained progression-free throughout the 2-year time frame for data collection for this outcome measure.

Time to progression in the brain due to treated metastases or new brain metastases. Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) was used to assess response. Progression was defined as an increase in tumor burden ≥25% relative to nadir (minimum recorded tumor burden), with confirmation by a repeat, consecutive assessment no less than 4 wk from the date first documented.

Outcome measures

Outcome measures
Measure	B: No Induction n=1 Participants Participants will undergo stereotactic radiosurgery (SRS) followed 2-3 weeks later by ipilimumab, which is given once every 3 weeks for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.	A: Induction n=3 Participants Patients will receive 2 doses of ipilimumab, which is given once every 3 weeks, prior to stereotactic radiosurgery (SRS), followed by 2 more doses of ipilimumab, for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.
Time to Progression 5 months, 27 days	0 participants	1 participants
Time to Progression 19 months, 3 days	1 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

Exploratory endpoints: Interval changes in dynamic MRI parameters such as perfusion, blood volume, vascular permeability (Ktrans), and diffusion tensor imaging; the change in 3D tumor volume.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

Exploratory endpoints: Interval changes in immune markers in the blood

Outcome measures

Outcome data not reported

Adverse Events

Ipilimumab and SRS

Serious events: 0 serious events

Other events: 4 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Ipilimumab and SRS n=4 participants at risk (Induction) Patients will receive 2 doses of ipilimumab, which is given once every 3 weeks, prior to stereotactic radiosurgery (SRS), followed by 2 more doses of ipilimumab, for a total of 4 doses. OR (No Induction) Participants will undergo stereotactic radiosurgery (SRS) followed 2-3 weeks later by ipilimumab, which is given once every 3 weeks for a total of 4 doses. Ipilimumab: Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. Stereotactic Radiosurgery: Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.
Investigations Alanine aminotransferase increased	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Psychiatric disorders Concentration impairment	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Gastrointestinal disorders Constipation	50.0% 2/4 • Number of events 2 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Investigations Creatinine increased	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Psychiatric disorders Depression	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Gastrointestinal disorders Diarrhea	50.0% 2/4 • Number of events 2 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Nervous system disorders Dizziness	50.0% 2/4 • Number of events 2 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Vascular disorders Edema limbs	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
General disorders Fatigue	75.0% 3/4 • Number of events 3 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
General disorders Fever	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Infections and infestations Flu like symptoms	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Nervous system disorders Headache	50.0% 2/4 • Number of events 2 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Nervous system disorders Hot flashes	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Metabolism and nutrition disorders Hyperglycemia	25.0% 1/4 • Number of events 2 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Investigations Decreased T4	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Investigations Vitamin D Deficiency	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Investigations Low Testosterone	25.0% 1/4 • Number of events 2 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Investigations Elevated LDH	25.0% 1/4 • Number of events 2 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Blood and lymphatic system disorders Lymphocyte count decreased	25.0% 1/4 • Number of events 2 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Musculoskeletal and connective tissue disorders Myalgia	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Skin and subcutaneous tissue disorders Nail discoloration	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Gastrointestinal disorders Nausea	25.0% 1/4 • Number of events 2 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Musculoskeletal and connective tissue disorders Neck pain	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Musculoskeletal and connective tissue disorders Pain in extremity	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Vascular disorders Periorbital edema	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Blood and lymphatic system disorders Platelet count decreased	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Skin and subcutaneous tissue disorders Pruritus	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Skin and subcutaneous tissue disorders Rash acneiform	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Skin and subcutaneous tissue disorders Rash maculo-papular	50.0% 2/4 • Number of events 2 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Nervous system disorders Tremor	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Nervous system disorders Vertigo	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.
Gastrointestinal disorders Vomiting	25.0% 1/4 • Number of events 1 • Adverse events were collected up to 6 months after study start. All-cause mortality is observed up to 5 years. Both arms were combined in the reporting of Adverse Events because both arms received the same two interventions.

Additional Information

Dr. Christopher Lao, MD, MPH

University of Michigan Comprehensive Cancer Center

Phone: (734) 936-4498

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place