Brain Metastases, AdultPhase 2NCT04434560
Neoadjuvant Immunotherapy in Brain Metastases
A Phase 2 study testing Nivolumab and Ipilimumab in people with Brain Metastases, Adult, run by Sarah Sammons, MD at 1 site in United States.
Trial summary
The purpose of this phase 2 study is to assess the feasibility and efficacy of neoadjuvant immunotherapy in patients with previously untreated, surgically-resectable, solid tumor brain metastases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases, Adult
- What is being tested?
- Nivolumab and Ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Nov 2020to 17 Jun 2021
- 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
- 1. Patients must have at least 1 previously untreated, solid tumor brain metastases that are ≤4 cm in the largest direction. At least one of the metastases must be surgically resectable. All metastases must be planned for treatment with SRS. Primary tumor histology must be one of the following:
- Squamous NSCLC
- Non-squamous NSCLC without known ALK, EGFR, and ROS mutation
- RCC
- Urothelial carcinoma
- Ovarian carcinoma
Show all 22Show fewer
- Melanoma
- Triple negative breast cancer that is PD-L1 positive
- Other solid tumor histologies may be eligible at the discretion of the PI if they are known to respond to immunotherapy containing regimens.
- 2. Patient must be asymptomatic or minimally symptomatic, requiring the equivalent of ≤ 4 mg dexamethasone daily for at least 7 days prior to enrollment
- 3. Patient or partner(s) meets one of the following criteria:
- Non-childbearing potential (i.e. not sexually active, physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile, or any male who has had a vasectomy). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Postmenopausal for purposes of this study is defined as 1 year without menses.; or
- Childbearing potential and agrees to use one of the following methods of birth control: approved hormonal contraceptives (e.g. birth control pills, patches, implants, or infusions), an intrauterine device, or a barrier method of contraception (e.g. a condom or diaphragm) used with spermicide.
- 4. Age ≥ 18 years of age at the time of entry into the study
- 5. Karnofsky Performance Score (KPS) ≥ 70
- 6. Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to resection
- 7. Neutrophil count ≥ 1000 prior to resection
- 8. Hemoglobin ≥ 9 g/dl prior to resection
- 9. Platelet count ≥ 100,000/µl unsupported is necessary for eligibility on the study; however, because of risks of intracranial hemorrhage during resection, platelet count ≥ 125,000/µl is required for the patient to undergo resection, which can be attained with the help of platelet transfusion
- 10. Creatinine ≤ 1.5 x ULN (upper limit of normal) prior to resection
- 11. A signed informed consent form approved by the Institutional Review Board (IRB) will be required for patient enrollment into the study. Patients must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study
- 12. Ability to undergo MRI
Who cannot join
- 1. Females who are pregnant or breast-feeding
- 2. Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate
- 3. Patients with severe, active co-morbidity, defined as follow:
- Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C)
- Patients with known immunosuppressive disease or known uncontrolled human immunodeficiency virus infection
- Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
Show all 13Show fewer
- 4. Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used:
- 5. Patients must not have received immunotherapy within 3 months prior to enrollment
- 6. Patients with prior, unrelated malignancy requiring current active treatment in the last 3 years with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
- 7. Patients with a known history of hypersensitivity to nivolumab, or any components of nivolumab
- 8. Patients with a known history of hypersensitivity to ipilimumab, or any components of ipilimumab
- 9. Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months.
- 10. History and/or confirmed pneumonitis, or extensive bilateral lung disease on high resolution/spiral CT scan.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Phase II Trial of Surgery and Stereotactic Radiosurgery With Neoadjuvant Nivolumab and Ipilimumab in Patients With Surgically-resectable, Solid Tumor Brain Metastases
The purpose of this phase 2 study is to assess the feasibility and efficacy of neoadjuvant immunotherapy in patients with previously untreated, surgically-resectable, solid tumor brain metastases. The primary objectives of this study are to 1) assess the feasibility of neoadjuvant ipilimumab and nivolumab treatment before surgery and stereotactic radiosurgery (SRS) in patients with solid tumor brain metastases as measured by the proportion of patients who have their surgery delayed or surgery never occurs, and 2) demonstrate that neoadjuvant immunotherapy will increase proliferation of circulating T-cells compared to baseline measurements. Exploratory objectives include describing patient progression free survival and overall survival, time to local and distant intracranial progression, and the rate of radiation necrosis. The rate of radionecrosis will also be explored, as immune expression profiles.
Read the detailed description
Forty patients planned for standard of care resection of at least one solid tumor brain metastasis will be enrolled onto the study after providing informed consent. Primary tumor histology types are restricted to those known to extracranially respond to immunotherapy, and will include, but not be limited to, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC without known anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), and ROS mutation, renal cell carcinoma (RCC), melanoma, and triple negative breast cancer (TNBC) that is programmed death-ligand 1 positive (PD-L1 +). All participants will receive neoadjuvant immunotherapy and will receive a single infusion of nivolumab at a dose of 3 mg/kg and ipilimumab at a dose of 1 mg/kg 7 days (±3 days) prior to surgical resection of their metastases. Approximately three weeks after resection, patients in will then receive SRS per standard of care guidelines. Patients will be followed for 18 months after initiating study treatment. Up to 20 participants will be recruited and treated. Blood will be collected periodically during the study for correlative assessments.
- Conditions
- Brain Metastases, Adult
- Being tested
- Nivolumab, Ipilimumab
- Keywords
- Pro00103812, Sammons, Non-small-cell lung carcinoma, Renal cell carcinoma, Urothelial carcinoma, Melanoma, Ovarian carcinoma, Triple negative breast cancer, Solid tumor, Brain metastases, Nivolumab, Ipilimumab, Opdivo, Yervoy
- Medical subject headings
- Brain Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Carcinoma, Transitional Cell, Melanoma, Ovarian Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
Nivolumab will be given at the FDA-approved dose of 3 mg/kg.
IpilimumabDrug
Also called Yervoy
Ipilimumab will be given at the FDA-approved dose of 1 mg/kg.
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care (no neoadjuvant immunotherapy) | No intervention | Patients will proceed to surgical resection with no nivolumab/ipilimumab given prior to surgery. |
| Neoadjuvant Immunotherapy | Experimental | Patients will receive a single dose of neoadjuvant nivolumab and ipilimumab 7 days (± 3 days) prior to surgical resection. Receives: Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients Who Have Their Surgery Delayed by More Than 4 Days or Surgery Never Occurs as a Direct or Indirect Result of Ipilimumab and Nivolumab Treatment.
Measured: 10 days
Proliferation of Circulating T-cells as Measured by Mean Fold-change Between Baseline and Day 1 in Ki67 Levels.
Ki-67 is a nuclear protein involved in cell proliferation regulation.
Measured: baseline to day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2020
- Study start4 Nov 2020
- Primary completion17 Jun 2021
- Study completion17 Jun 2021
Why it stopped: Poor enrollment
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 Brain Metastases, AdultStudies of the same condition, open and under way.
- 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
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sarah Sammons, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Duke University
- Responsible party
- Sponsor-investigator, Sarah Sammons, MD, Duke University
- Investigators
- Sarah Sammons, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04434560
- Sponsor's protocol ID
- Pro00103812
- Other IDs
- CA184-583
- Status last verified
- Jul 2022
- First submitted
- 12 Jun 2020
- Last updated
- 26 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Surgery and Stereotactic Radiosurgery With Neoadjuvant Nivolumab and Ipilimumab in Patients With Surgically-resectable, Solid Tumor Brain Metastases
- ClinicalTrials.gov ID
- NCT04434560
- Acronym / sponsor ID
- Pro00103812
- Conditions
- Brain Metastases, Adult
- Keywords
- Pro00103812, Sammons, Non-small-cell lung carcinoma, Renal cell carcinoma, Urothelial carcinoma, Melanoma, Ovarian carcinoma, Triple negative breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor enrollment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Sarah Sammons, MDUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Duke University
- Study start
- 4 Nov 2020 (actual)
- Primary completion
- 17 Jun 2021 (actual)
- Study completion
- 17 Jun 2021 (actual)
- First posted
- 17 Jun 2020 (actual)
- Results
- Posted 26 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this phase 2 study is to assess the feasibility and efficacy of neoadjuvant immunotherapy in patients with previously untreated, surgically-resectable, solid tumor brain metastases. The primary objectives of this study are to 1) assess the feasibility of neoadjuvant ipilimumab and nivolumab treatment before surgery and stereotactic radiosurgery (SRS) in patients with solid tumor brain metastases as measured by the proportion of patients who have their surgery delayed or surgery never occurs, and 2) demonstrate that neoadjuvant immunotherapy will increase proliferation of circulating T-cells compared to baseline measurements. Exploratory objectives include describing patient progression free survival and overall survival, time to local and distant intracranial progression, and the rate of radiation necrosis. The rate of radionecrosis will also be explored, as immune expression profiles.
Detailed description
Forty patients planned for standard of care resection of at least one solid tumor brain metastasis will be enrolled onto the study after providing informed consent. Primary tumor histology types are restricted to those known to extracranially respond to immunotherapy, and will include, but not be limited to, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC without known anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), and ROS mutation, renal cell carcinoma (RCC), melanoma, and triple negative breast cancer (TNBC) that is programmed death-ligand 1 positive (PD-L1 +). All participants will receive neoadjuvant immunotherapy and will receive a single infusion of nivolumab at a dose of 3 mg/kg and ipilimumab at a dose of 1 mg/kg 7 days (±3 days) prior to surgical resection of their metastases. Approximately three weeks after resection, patients in will then receive SRS per standard of care guidelines. Patients will be followed for 18 months after initiating study treatment. Up to 20 participants will be recruited and treated. Blood will be collected periodically during the study for correlative assessments.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care (no neoadjuvant immunotherapy) | No intervention | –Patients will proceed to surgical resection with no nivolumab/ipilimumab given prior to surgery. |
| Neoadjuvant Immunotherapy | Experimental | Drug: Nivolumab, Drug: IpilimumabPatients will receive a single dose of neoadjuvant nivolumab and ipilimumab 7 days (± 3 days) prior to surgical resection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 1. Patients must have at least 1 previously untreated, solid tumor brain metastases that are ≤4 cm in the largest direction. At least one of the metastases must be surgically resectable. All metastases must be planned for treatment with SRS. Primary tumor histology must be one of the following:
- 2. Patient must be asymptomatic or minimally symptomatic, requiring the equivalent of ≤ 4 mg dexamethasone daily for at least 7 days prior to enrollment
- 3. Patient or partner(s) meets one of the following criteria:
- 4. Age ≥ 18 years of age at the time of entry into the study
- 5. Karnofsky Performance Score (KPS) ≥ 70
Key exclusion criteria (13 listed)
- 1. Females who are pregnant or breast-feeding
- 2. Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate
- 3. Patients with severe, active co-morbidity, defined as follow:
- 4. Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used:
- 5. Patients must not have received immunotherapy within 3 months prior to enrollment
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 |
|---|---|---|
| NivolumabAlso: OpdivoNivolumab will be given at the FDA-approved dose of 3 mg/kg. | Drug | Neoadjuvant Immunotherapy |
| IpilimumabAlso: YervoyIpilimumab will be given at the FDA-approved dose of 1 mg/kg. | Drug | Neoadjuvant Immunotherapy |
Primary outcome
Proportion of Patients Who Have Their Surgery Delayed by More Than 4 Days or Surgery Never Occurs as a Direct or Indirect Result of Ipilimumab and Nivolumab Treatment.
Time frame: 10 days
Proliferation of Circulating T-cells as Measured by Mean Fold-change Between Baseline and Day 1 in Ki67 Levels.
Time frame: baseline to day 1
Ki-67 is a nuclear protein involved in cell proliferation regulation.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The Preston Robert Tisch Brain Tumor CenterLink provided by the sponsor.
- Duke HealthLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Brain Metastases, Adult
RecruitingPhase 3
Testing a New Treatment Strategy to Improve Secondary Stroke Prevention for Older Adults: The STROKE75+ Trial
Stroke, Ischemic
RecruitingObservational study
Circulating Biomarkers Repository in Adults Diagnosed With Primary and Metastatic Brain Tumors
Brain Tumor, Primary, Brain Metastases, Adult
Not yet recruitingPhase 2
Study of Tovorafenib in High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG)
High Grade Glioma (HGG) of the Brain With BRAF Aberration, High Grade Glioma (III or IV)
RecruitingObservational study
A Study to Develop a Blood-based Test for Aiding the Diagnosis/Prognosis of Traumatic Brain Injury in Adults and for Monitoring the Development of Secondary Events in Patients Diagnosed With Traumatic Brain Injury
Traumatic Brain Injury
RecruitingPhase 1
IL-8 Receptor Modified Patient-Derived Activated CD70 CAR T Cell Therapy in Adults With Brain Metastases
Brain Metastases
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.
Sarah Sammons, MD principal investigator
Duke University
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 Nivolumab and Ipilimumab in people with Brain Metastases, Adult, run by Sarah Sammons, MD 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 22 inclusion and 13 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 26 Jul 2022. 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 26 Jul 2022). 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?
Proportion of Patients Who Have Their Surgery Delayed by More Than 4 Days or Surgery Never Occurs as a Direct or Indirect Result of Ipilimumab and Nivolumab Treatment. (time frame: 10 days). The study lists 2 primary outcomes in all. 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 26 Jul 2022.