Metastatic MelanomaPhase 2NCT02097732
Ipilimumab Induction in Patients With Melanoma Brain Metastases Receiving Stereotactic Radiosurgery
A Phase 2 study testing Ipilimumab and Stereotactic Radiosurgery in people with Metastatic Melanoma and Brain Metastases, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
This is a study to test the efficacy of using standard immune therapy for melanoma prior to stereotactic radiosurgery (ipilimumab induction), as compared to stereotactic radiosurgery followed by immune therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma, Brain Metastases
- What is being tested?
- Ipilimumab and Stereotactic Radiosurgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to Jul 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with a histologically-confirmed diagnosis of melanoma who have imaging findings suggestive of 1 to 4 brain metastases
- At least one lesion in the brain that is measurable, which is defined as ≥5 x 5mm (Prior craniotomy and surgical resection is allowed, as long as there is at least one remaining measurable lesion in the brain)
- Patients must be candidates for stereotactic radiosurgery (SRS) and planning to undergo SRS
- Patients must be candidates for ipilimumab as determined by the treating physician
- Patients must be neurologically asymptomatic, or very minimally symptomatic, as judged by the treating physicians
- At least 3 weeks has elapsed from any prior therapy, and the patient has recovered from side effects to ≤ grade 1 toxicities per Common Terminology Criteria (CTC) for Adverse Events
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- Age > or = 18 years old
- Performance status of ECOG of 0 or 1 (ECOG is the Eastern Oncology Cooperative Group Scoring system used to quantify cancer patients' general well-being and activities of daily life; scores range from 0 to 5 where 0 is perfect health and 5 is death)
- Adequate organ and marrow function: alanine aminotransferase (ALT ) < 2.5x's upper limit of normal (ULN) of the institutional normal reference range, aspartate aminotransferase (AST) < 2.5x's ULN of the institutional normal reference range, Bilirubin < 1.5x's ULN of the institutional normal reference range, Creatinine < 2.0 milligrams per deciliter, Platelets > 50,000 per microliter
- Women of child-bearing potential must agree to use adequate contraception, defined as complete abstinence from intercourse with men or two methods
- Ability to understand and the willingness to sign a written informed consent
Who cannot join
- Previous radiotherapy to the lesion(s) of interest, including prior treatment with whole brain radiation therapy (WBRT). Prior treatment with SRS is allowed if the index lesion(s) is in a different, non-contiguous location than the previously treated lesion.
- Patients who have previously received ipilimumab, PD-1 inhibitors or PD-L1 inhibitors are excluded due to the potential of effects on primary outcome
- Patients who require WBRT or surgery at the time of enrollment
- Neurologic symptoms or imaging findings that necessitate the use of steroids on the day of enrollment or in the prior 7 days
- Highly suspicious magnetic resonance imaging (MRI) or cerebrospinal fluid evidence of leptomeningeal metastases, unless all measurable disease is localized and SRS is considered the treatment of choice
- Concurrent treatment with any other anti-neoplastic drug or concurrent participation in another therapeutic clinical trial
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- Patients unable to undergo or tolerate MRI scans (presence of cardiac pacemaker, implanted cardiac defibrillator, aneurysm clips, history of allergic reaction/hypersensitivity to gadolinium)
- Women who are pregnant or are nursing
- Patients with absolute lymphocyte count of <500 cells/microliter, who are known to be HIV positive, who have clinically significant active autoimmune disease, or are receiving immunosuppression following solid organ or stem cell transplant
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Hospital
Ann Arbor, Michigan, 48109
About this study
This is a study to test the efficacy of using standard immune therapy for melanoma prior to stereotactic radiosurgery (ipilimumab induction), as compared to stereotactic radiosurgery followed by immune therapy. The study's hypothesis is that ipilimumab induction is as good as or better than controlling brain metastases as compared to stereotactic radiosurgery followed by immune therapy.
Read the detailed description
This is a randomized Phase II selection study investigating the use of ipilimumab induction prior to stereotactic radiosurgery (SRS), versus no induction, for melanoma brain metastases. Participants will be randomized to Arm A "Induction" (two doses of ipilimumab prior to SRS, two doses of ipilimumab after SRS) versus Arm B "No induction" (SRS first, followed by 4 doses of ipilimumab). Participants will undergo multiple dynamic contrast-enhanced MRIs of the brain and submit blood samples for immune testing.
- Conditions
- Metastatic Melanoma, Brain Metastases
- Being tested
- Ipilimumab, Stereotactic Radiosurgery
- Keywords
- Metastatic melanoma, Brain metastases, Radiation therapy, Immune therapy
- Medical subject headings
- Melanoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
Ipilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses.
Stereotactic RadiosurgeryProcedure or surgery
Stereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours.
| Study group | Role | What they receive |
|---|---|---|
| B: No induction | Active comparator | 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. Receives: Drug: Ipilimumab; Procedure: Stereotactic Radiosurgery |
| A: Induction | Experimental | 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. Receives: Drug: Ipilimumab; Procedure: Stereotactic Radiosurgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local Control Rate
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.
Measured: 6 months
Secondary outcomes (4)
Overall Survival Rate
Number of participants alive at 5 years after enrollment.
Measured: Up to 5 years
Regional (Intracranial) Control Rate
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.
Measured: 6 months
Intracranial Response Rate
Response of treated (irradiated) brain metastases to combination therapy with ipilimumab and stereotactic radiosurgery using immune-related response criteria.
Measured: Up to 12 months
Time to Progression
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.
Measured: From date of enrollment to up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2014 (estimated)
- Study startApr 2014
- Primary completionAug 2016
- Study completionJul 2020
Why it stopped: Study halted prematurely due to a change in the standard of care treatment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christopher Lao, M.D., Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02097732
- Sponsor's protocol ID
- UMCC 2013.114
- Other IDs
- HUM00082134
- Status last verified
- Apr 2021
- First submitted
- 24 Mar 2014
- Last updated
- 12 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ipilimumab Induction in Patients With Melanoma Brain Metastases Receiving Stereotactic Radiosurgery
- ClinicalTrials.gov ID
- NCT02097732
- Acronym / sponsor ID
- UMCC 2013.114
- Conditions
- Metastatic Melanoma, Brain Metastases
- Keywords
- Metastatic melanoma, Brain metastases, Radiation therapy, Immune therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study halted prematurely due to a change in the standard of care treatment
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Aug 2016 (actual)
- Study completion
- Jul 2020 (actual)
- First posted
- 27 Mar 2014 (estimated)
- Results
- Posted 19 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study to test the efficacy of using standard immune therapy for melanoma prior to stereotactic radiosurgery (ipilimumab induction), as compared to stereotactic radiosurgery followed by immune therapy. The study's hypothesis is that ipilimumab induction is as good as or better than controlling brain metastases as compared to stereotactic radiosurgery followed by immune therapy.
Detailed description
This is a randomized Phase II selection study investigating the use of ipilimumab induction prior to stereotactic radiosurgery (SRS), versus no induction, for melanoma brain metastases. Participants will be randomized to Arm A "Induction" (two doses of ipilimumab prior to SRS, two doses of ipilimumab after SRS) versus Arm B "No induction" (SRS first, followed by 4 doses of ipilimumab). Participants will undergo multiple dynamic contrast-enhanced MRIs of the brain and submit blood samples for immune testing.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| B: No induction | Active comparator | Drug: Ipilimumab, Procedure: Stereotactic RadiosurgeryParticipants 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. |
| A: Induction | Experimental | Drug: Ipilimumab, Procedure: Stereotactic RadiosurgeryPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with a histologically-confirmed diagnosis of melanoma who have imaging findings suggestive of 1 to 4 brain metastases
- At least one lesion in the brain that is measurable, which is defined as ≥5 x 5mm (Prior craniotomy and surgical resection is allowed, as long as there is at least one remaining measurable lesion in the brain)
- Patients must be candidates for stereotactic radiosurgery (SRS) and planning to undergo SRS
- Patients must be candidates for ipilimumab as determined by the treating physician
- Patients must be neurologically asymptomatic, or very minimally symptomatic, as judged by the treating physicians
Key exclusion criteria (9 listed)
- Previous radiotherapy to the lesion(s) of interest, including prior treatment with whole brain radiation therapy (WBRT). Prior treatment with SRS is allowed if the index lesion(s) is in a different, non-contiguous location than the previously treated lesion.
- Patients who have previously received ipilimumab, PD-1 inhibitors or PD-L1 inhibitors are excluded due to the potential of effects on primary outcome
- Patients who require WBRT or surgery at the time of enrollment
- Neurologic symptoms or imaging findings that necessitate the use of steroids on the day of enrollment or in the prior 7 days
- Highly suspicious magnetic resonance imaging (MRI) or cerebrospinal fluid evidence of leptomeningeal metastases, unless all measurable disease is localized and SRS is considered the treatment of choice
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IpilimumabIpilimumab 3mg/kg given intravenously over 90 minutes, every 3 weeks for a total of 4 doses. | Drug | A: Induction, B: No induction |
| Stereotactic RadiosurgeryStereotactic radiosurgery is a type of focused radiation therapy. It requires the placement of a metal frame on the head for several hours. | Procedure or surgery | A: Induction, B: No induction |
Primary outcome
Local Control Rate
Time frame: 6 months
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.
4 secondary outcomes
Overall Survival Rate
Time frame: Up to 5 years
Regional (Intracranial) Control Rate
Time frame: 6 months
Intracranial Response Rate
Time frame: Up to 12 months
Time to Progression
Time frame: From date of enrollment to up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Lao, M.D. principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ipilimumab and Stereotactic Radiosurgery in people with Metastatic Melanoma and Brain Metastases, run by University of Michigan Rogel Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local Control Rate (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2021.