NCT04434560

Neoadjuvant Immunotherapy in Brain Metastases

Terminated Phase 2 Results posted Last updated 26 July 2022

What this trial tests

Phase 2 trial testing Nivolumab in Brain Metastases, Adult in 1 participant. Terminated before completion.

Timeline

4 November 2020

Primary endpoint
17 June 2021

17 June 2021

Quick facts

Lead sponsor	Sarah Sammons, MD
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	1
Start date	4 November 2020
Primary completion	17 June 2021
Estimated completion	17 June 2021
Sites	1 location across United States

Drugs / interventions tested

• Nivolumab (nivolumab) — full drug profile →
• Ipilimumab — full drug profile →

Conditions studied

• Brain Metastases, Adult — all drugs for Brain Metastases, Adult →

Sponsor

Sarah Sammons, MD

Who can join

18 and older, any sex, with Brain Metastases, Adult. Patients with the condition only — healthy volunteers not accepted.

Adverse events — posted to ClinicalTrials.gov

Time frame: Approximately 10 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Standard of Care (no Neoadjuvant Immunotherapy)

Serious: 1/1 (100%)

Deaths: 0/1

Neoadjuvant Immunotherapy

Serious: 0

Deaths: 0

Serious adverse events (1 terms)

Reaction	System	Standard of Care (no Neoad…	Neoadjuvant Immunotherapy
Pyramidal tract syndrome	Nervous system disorders	—	—

Other adverse events (12 terms — click to expand)

Reaction	System	Standard of Care (no Neoad…	Neoadjuvant Immunotherapy
Anemia	Blood and lymphatic system disorders	—	—
Hypothyroidism	Endocrine disorders	—	—
Lymphocyte count decreased	Investigations	—	—
Platelet count decreased	Investigations	—	—
White blood cell decreased	Investigations	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—
Hypomagnesemia	Metabolism and nutrition disorders	—	—
Concentration impairment	Nervous system disorders	—	—
Dysphasia	Nervous system disorders	—	—
Headache	Nervous system disorders	—	—
Paresthesia	Nervous system disorders	—	—
Pyramidal tract syndrome	Nervous system disorders	—	—

Most-reported serious reactions: Pyramidal tract syndrome.

Data from ClinicalTrials.gov NCT04434560 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Breast Cancer Brain Metastasis-Overview of Disease State, Treatment Options and Future Perspectives.
   Watase C, Shiino S, Shimoi T, Noguchi E, et al · · 2021 · cited 68× · PMID 33802424 · DOI 10.3390/cancers13051078
2. Breast Cancer Brain Metastasis: A Comprehensive Review.
   Raghavendra AS, Ibrahim NK. · · 2024 · cited 45× · PMID 38748968 · DOI 10.1200/op.23.00794
3. Emerging principles of brain immunology and immune checkpoint blockade in brain metastases.
   Fares J, Ulasov I, Timashev P, Lesniak MS. · · 2021 · cited 40× · PMID 33893488 · DOI 10.1093/brain/awab012
4. Central Nervous System Metastases from Triple-Negative Breast Cancer: Current Treatments and Future Prospective.
   Kadamkulam Syriac A, Nandu NS, Leone JP. · · 2022 · cited 36× · PMID 35046721 · DOI 10.2147/bctt.s274514
5. Immunotherapy for triple-negative breast cancer: A molecular insight into the microenvironment, treatment, and resistance.
   Bai X, Ni J, Beretov J, Graham P, et al · · 2021 · cited 33× · PMID 39036372 · DOI 10.1016/j.jncc.2021.06.001
6. Modern Immunotherapy in the Treatment of Triple-Negative Breast Cancer.
   Wesolowski J, Tankiewicz-Kwedlo A, Pawlak D. · · 2022 · cited 20× · PMID 36010854 · DOI 10.3390/cancers14163860
7. Prognostic Factors and Current Treatment Strategies for Renal Cell Carcinoma Metastatic to the Brain: An Overview.
   Internò V, De Santis P, Stucci LS, Rudà R, et al · · 2021 · cited 16× · PMID 33925585 · DOI 10.3390/cancers13092114
8. Harnessing nanomedicine for enhanced immunotherapy for breast cancer brain metastases.
   Carney CP, Pandey N, Kapur A, Woodworth GF, et al · · 2021 · cited 15× · PMID 34716900 · DOI 10.1007/s13346-021-01039-9