Radiotherapy + Immunotherapy for Melanoma Brain Metastasis
Recruiting in Palo Alto (17 mi)
Overseen byMohammad K Khan, MD, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Emory University
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests a new combination of treatments for melanoma that has spread to the brain. It uses precise radiation, immune-boosting drugs, and a device that sends electric fields to disrupt cancer cells. The goal is to see if this combination is safe and more effective than current treatments.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you must not be on systemic steroids above 20 mg prednisone equivalent or 4 mg dexamethasone per day within 7 days prior to the trial. You also need to have recovered from any prior treatments at least 14 days before enrollment. It's best to discuss your specific medications with the trial team.
What data supports the idea that Radiotherapy + Immunotherapy for Melanoma Brain Metastasis is an effective treatment?
The available research shows that combining radiotherapy with immunotherapy, like ipilimumab or nivolumab, is effective for treating melanoma brain metastases. Studies indicate that this combination improves outcomes compared to using radiotherapy alone. For example, one study found that patients receiving both ipilimumab and stereotactic radiosurgery had better results than those who only received stereotactic radiosurgery. This suggests that the combination treatment can be more effective in controlling the disease in the brain.
12345What safety data exists for radiotherapy and immunotherapy in treating melanoma brain metastases?
Several studies have evaluated the safety of combining radiotherapy with immunotherapy for melanoma brain metastases. A Phase 1 study assessed the safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT), focusing on determining the maximum tolerable dose. Another study investigated the safety of concurrent SRS with ipilimumab or nivolumab, highlighting brain control and toxicity. A comparison of ipilimumab and SRS versus SRS alone for newly diagnosed cases also provided safety insights. Additionally, a retrospective review of pembrolizumab combined with SRS reported radiation necrosis in 6.8% of cases, with no other significant adverse events. Lastly, a toxicity analysis of SRS with combined ipilimumab and nivolumab therapy indicated promising results, with a focus on the timing of treatments.
12467Is the treatment of radiotherapy combined with the drugs Ipilimumab, Nivolumab, and Pembrolizumab promising for melanoma brain metastasis?
Yes, combining radiotherapy with the drugs Ipilimumab, Nivolumab, and Pembrolizumab shows promise for treating melanoma brain metastasis. Studies suggest that this combination can improve survival rates and control the spread of cancer in the brain.
128910Eligibility Criteria
This trial is for adults with melanoma that has spread to the brain. Participants must be in good health otherwise, able to consent, and have not received certain treatments recently. They should also agree to use birth control if of childbearing potential and need a caregiver or self-support for device management.Inclusion Criteria
Female subject of childbearing potential must have a negative urine or serum pregnancy within 2 weeks prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
I haven't had immunotherapy, or if I did, it was approved by the study leader due to limited disease progression.
I am using two birth control methods or am not having sex to join this study.
+27 more
Exclusion Criteria
You have signs of high pressure inside your head.
I haven't had cancer treatment in the last 2 weeks or I've recovered from its side effects.
I have only received the flu shot, not the nasal spray vaccine.
+26 more
Participant Groups
The study tests combining stereotactic radiosurgery (precise radiation therapy) with immune checkpoint inhibitors (drugs like pembrolizumab, nivolumab, ipilimumab) and NovoTTF-100M (a device creating electric fields to disrupt cancer cells). The goal is to see if this combo works better than current methods.
2Treatment groups
Experimental Treatment
Group I: Arm II (nivolumab, ipilimumab, SRS, TTFields)Experimental Treatment4 Interventions
Patients receive standard of care nivolumab and ipilimumab and undergo 3-5 fractions SRS. Patients also undergo TTFields over 8 hours daily using NovoTTF-100M device until intra-cranial progression or until end of immunotherapy treatments at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity.
Group II: Arm I (SRS, pembrolizumab, TTFields)Experimental Treatment3 Interventions
Patients receive standard of care pembrolizumab and undergo 3-5 fractions SRS. Patients also undergo TTFields over 8 hours daily using NovoTTF-100M device until intra-cranial progression or until end of immunotherapy treatments at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity.
Ipilimumab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Yervoy for:
- Advanced melanoma
- Stage III unresectable melanoma
- Stage IV metastatic melanoma
🇪🇺 Approved in European Union as Yervoy for:
- Advanced melanoma
- Stage III unresectable melanoma
- Stage IV metastatic melanoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Emory University Hospital/Winship Cancer InstituteAtlanta, GA
Loading ...
Who Is Running the Clinical Trial?
Emory UniversityLead Sponsor
NovoCure Ltd.Industry Sponsor
National Cancer Institute (NCI)Collaborator
References
Phase 1 Study of Ipilimumab Combined With Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients With Brain Metastases. [2022]We performed a phase 1 study to determine the maximum tolerable dose and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) in patients with brain metastases from melanoma.
Stereotactic radiosurgery combined with nivolumab or Ipilimumab for patients with melanoma brain metastases: evaluation of brain control and toxicity. [2020]To investigate the efficacy and safety of concurrent stereotactic radiosurgery (SRS) and ipilimumab or nivolumab in patients with untreated melanoma brain metastases.
Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity. [2020]There is evidence that the combination of ipilimumab and stereotactic radiosurgery (SRS) for brain metastases improves outcomes. We investigated clinical outcomes, radiation toxicity, and impact of ipilimumab timing in patients treated with SRS for melanoma brain metastases.
Ipilimumab and Stereotactic Radiosurgery Versus Stereotactic Radiosurgery Alone for Newly Diagnosed Melanoma Brain Metastases. [2022]We compared the safety and efficacy of ipilimumab and stereotactic radiosurgery (SRS) to SRS alone for newly diagnosed melanoma brain metastases (MBM).
Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment. [2022]Ipilimumab (Ipi), a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, has been shown to improve survival in patients with metastatic melanoma. In this single-institution study, we investigated the safety and efficacy of stereotactic radiosurgery (SRS) for patients with melanoma brain metastases (BMs) who also received Ipi.
Tolerance and outcomes of stereotactic radiosurgery combined with anti-programmed cell death-1 (pembrolizumab) for melanoma brain metastases. [2019]Anti-programmed cell death-1 (anti-PD1) antibodies are currently the first-line treatment for patients with metastatic BRAF wild-type melanoma, alone or combined with the anti-CTLA4 monoclonal antibody, ipilimumab. To date, data on safety and the outcomes of patients treated with the anti-PD1 monoclonal antibodies, pembrolizumab (PB), or nivolumab, combined with stereotactic radiosurgery (SRS), for melanoma brain metastases (MBM) are scarce. We retrospectively reviewed all patients with MBM treated with PB combined with SRS between 2012 and 2015. The primary endpoint was neurotoxicity. The secondary endpoints were local, distant intracranial controls and overall survival (OS). Among 74 patients with MBM treated with SRS, 25 patients with a total of 58 MBM treated with PB combined with SRS within 6 months were included. Radiation necrosis, occurring within a median time of 6.5 months, was observed for four MBM (6.8%) in four patients. No other significant SRS-related adverse event was observed. After a median follow-up of 8.4 months, local control was achieved in 46 (80%) metastases and 17 (68%) patients. Perilesional oedema and intratumour haemorrhage appearing or increasing after SRS were associated with local progression (P
Stereotactic radiosurgery and combined immune checkpoint therapy with ipilimumab and nivolumab in patients with melanoma brain metastases: A retrospective monocentric toxicity analysis. [2023]Adding stereotactic radiosurgery (SRS) to combined immune checkpoint therapy with ipilimumab and nivolumab (IPI + NIVO) has led to promising results for patients with melanoma brain metastases (MBM). This study retrospectively analyzes the toxicity profile depending on the timing of SRS with regard to IPI + NIVO.
Stereotactic radiosurgery with immunotherapy is associated with improved overall survival in patients with metastatic melanoma or non-small cell lung cancer: a National Cancer Database analysis. [2022]Immunotherapy is now a first-line treatment for metastatic non-small cell lung cancer (NSCLC) and melanomaQuery. It is important to understand the relationship between immunotherapy and radiation to the brain. The aim of this study was to assess the role of stereotactic radiosurgery (SRS) or WBRT in addition to immunotherapy in patients with melanoma or NSCLC metastatic to the brain.
Systemic therapy augmented by radiotherapy (STAR) effect for brain metastases in a BRAF-mutated melanoma patient with prolonged survival: a case report. [2021]Brain metastases are common in stage IV malignant melanoma, carrying a prognosis traditionally regarded as severe, with a median survival of few months. Recently introduced systemic therapies as targeted therapy or immunotherapy have significantly improved the prognosis of metastatic melanoma. The optimal association of radiotherapy to such novel treatments has to be clarified. We report on a 43-year-old woman with 10 brain metastases. Three of them were treated with stereotactic radiosurgery (SRS) with complete response even of the untreated lesions. As the patient was BRAF-mutated, she was started on dabrafenib/trametinib. After 8 months she developed new brain metastases, which again responded to a new treatment with SRS. As after 7 months additional lesions appeared, she was treated with whole brain radiotherapy and was started on nivolumab. Twenty months after the first diagnosis of brain metastases the patient is fit without significant clinical and radiological signs of toxicity.
Impact of cranial stereotactic radiotherapy associated with immunotherapy with nivolumab and ipilimumab on overall survival in patients with melanoma brain metastases: a real-world evidence. [2022]To evaluate the impact of cranial stereotactic radiotherapy (SRT) on overall survival (OS) of melanoma brain metastases (MBM) patients treated with combined nivolumab and ipilimumab (CNI) in a contemporary and real-world setting.