Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
No Placebo Group
Prior Safety Data
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?This trial is testing if adding radiation to lymph nodes along with immune-boosting medicine helps prevent cancer from coming back in patients with a specific type of skin cancer. It focuses on patients who have a high risk of their cancer spreading to their lymph nodes and are already planned to receive immunotherapy.
What data supports the idea that Radiation Therapy for Melanoma is an effective treatment?The available research shows that combining radiation therapy with immunotherapy can be effective for treating melanoma, especially in cases where other treatments have failed. Studies indicate that radiation therapy can help the immune system better recognize and attack cancer cells, potentially improving the overall response to treatment. For example, one study found that using radiation therapy alongside immunotherapy helped patients who did not respond to a drug called nivolumab. Another study highlighted that this combination could be safe and might improve survival outcomes, although more research is needed to confirm these findings. Overall, radiation therapy appears to be a promising option, especially for advanced melanoma cases.3781013
Do I have to stop taking my current medications for the trial?The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves radiation therapy and immunotherapy, it's important to discuss your current medications with the trial team to ensure there are no interactions.
Is the treatment Immunotherapy promising for melanoma when combined with radiation therapy?Yes, combining immunotherapy with radiation therapy for melanoma is promising. Studies show that this combination can enhance the body's immune response against cancer, potentially improving treatment outcomes. This approach has shown positive results in clinical trials and is considered a safe and effective option for treating melanoma.124610
What safety data is available for radiation therapy in treating melanoma?Safety data for radiation therapy in treating melanoma includes studies on the combination of immune checkpoint inhibitors and palliative radiotherapy, which focus on immune-related adverse events. Anti-PD-1 therapies, such as nivolumab and pembrolizumab, are generally better tolerated than conventional treatments but can still cause mild to severe immune-related adverse events. The safety of combined immunotherapy and thoracic radiation therapy has been evaluated in phase 1/2 trials, and a phase 1 trial has assessed the safety of ipilimumab with stereotactic body radiation therapy in metastatic melanoma. Overall, while many adverse events are mild and manageable, there is a need for further understanding and prevention of severe adverse events.5791112
Eligibility Criteria
This trial is for adults with high-risk melanoma that's spread to sentinel lymph nodes but not elsewhere, who haven't had all their affected lymph nodes removed and are set for immunotherapy. They should be fairly active (ECOG β€3), able to follow up, have a life expectancy over 6 months, and use contraception if capable of childbearing.Inclusion Criteria
I can take care of myself but cannot do heavy physical work.
My cancer has not spread to distant parts of my body.
I am scheduled for immunotherapy after surgery.
My melanoma has spread to my lymph nodes with high-risk features.
Exclusion Criteria
I am an adult who can make my own medical decisions, not pregnant, and not incarcerated.
I have had all lymph nodes removed where cancer was found.
My cancer has spread to distant parts of my body.
I am currently pregnant.
I have had radiation therapy before in the same area that needs treatment now.
Treatment Details
The study is testing whether radiation therapy on the lymph nodes after a biopsy can lower the chance of cancer returning in those nodes for patients with high-risk melanoma starting immunotherapy, without removing more lymph nodes.
2Treatment groups
Experimental Treatment
Active Control
Group I: Group I (immunotherapy, radiation therapy)Experimental Treatment3 Interventions
Within 12 weeks of SLNB, patients start nodal radiation therapy (30 Gy in 5 treatments over 2-2.5 weeks). Immunotherapy planned to begin at any time after SLNB.
Group II: Group II (immunotherapy)Active Control2 Interventions
Patients planned to undergo immunotherapy.
Immunotherapy is already approved in European Union, United States, Canada for the following indications:
πͺπΊ Approved in European Union as Various Immunotherapies for:
- Melanoma
- Non-Hodgkin lymphoma
- Chronic myelogenous leukemia (CML)
- Kidney cancer
- Breast cancer
- Prostate cancer
πΊπΈ Approved in United States as Various Immunotherapies for:
- Melanoma
- Non-Hodgkin lymphoma
- Chronic myelogenous leukemia (CML)
- Kidney cancer
- Breast cancer
- Prostate cancer
- Bladder cancer
π¨π¦ Approved in Canada as Various Immunotherapies for:
- Melanoma
- Non-Hodgkin lymphoma
- Chronic myelogenous leukemia (CML)
- Kidney cancer
- Breast cancer
- Prostate cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
Cooper Hospital UNIV MED CTR.Camden, NJ
M D Anderson Cancer CenterHouston, TX
Baptist - MD Anderson Cancer CenterJacksonville, FL
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Who is running the clinical trial?
M.D. Anderson Cancer CenterLead Sponsor
References
Combining radiation and immunotherapy for synergistic antitumor therapy. [2021]The combination of radiation therapy and immunotherapy holds enticing promise as a strategy for cancer treatment. Preclinical studies have shown that radiation may act synergistically with immunotherapy to enhance or broaden antitumor immune responses, in part, because of radiation-induced phenotypic alterations of tumor cells that render them more susceptible to immune-mediated killing. Clinical trials utilizing the combination of therapeutic vaccines with radiation have supported many of these findings, and other clinical trials are both ongoing and planned. This review examines the evidence that radiation induces immunological death, the mechanisms by which radiation therapy can induce or augment antitumor immune responses, and translational studies demonstrating that immunotherapy can be effectively combined with radiation therapy. Finally, recent and current clinical trials combining radiation therapy with immunotherapy are reviewed.
Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes. [2021]Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-Ξ± and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.
Acute skin reaction suggestive of pembrolizumab-induced radiosensitization. [2015]The combination of localized radiotherapy and immune checkpoint inhibitors represents a promising therapeutic strategy for various cancers, including metastatic melanoma. Radiation therapy may enhance tumor antigen presentation and cytokine release, which may optimize the systemic antitumor immune response induced by these immunotherapeutic antibodies, with a potential delayed abscopal effect. However, clinical experience of using immune checkpoint inhibitors with concurrent radiotherapy remains scarce. We report here for the first time a case suggestive of acute skin radiosensitization induced by pembrolizumab, with a suggestive time relationship between the completion of ionizing radiation, drug administration, and rapid onset of the skin reaction. This suggests that radiation therapy may also interact rapidly with anti-programmed-death 1 antibodies. Therefore, caution should be exercised when prescribing this combination therapy in advanced cancers.
Radiotherapy and immune checkpoints inhibitors for advanced melanoma. [2018]The therapeutic landscape of metastatic melanoma drastically changed after the introduction of targeted therapies and immunotherapy, in particular immune checkpoints inhibitors (ICI). In recent years, positive effects on the immune system associated to radiotherapy (RT) were discovered, and radiation has been tested in combination with ICI in both pre-clinical and clinical studies (many of them still ongoing). We here summarize the rationale and the preliminary clinical results of this approach.
The safety of anti PD-1 therapeutics for the treatment of melanoma. [2018]The introduction of immunotherapies into clinical practice has substantially improved the prognosis of metastatic melanoma patients as well as patients suffering from other cancers. The two FDA-approved checkpoint inhibitors against PD-1 (nivolumab and pembrolizumab) have been shown to significantly improve patient survival while being less toxic than previous treatment options. Areas covered: The current scientific literature on safety and adverse events (AEs) related to anti-PD-1 therapies has been investigated with special attention to case reports and to the latest results announced at the major clinical cancer and melanoma meetings, including ASCO (American Society of Clinical Oncology), ESMO (European Society of medical Oncology) and EADO (European Association of Dermato-Oncology) annual meetings. Expert opinion: Even though anti-PD-1 therapies are better tolerated than conventional chemo- or other immune-therapies, they still induce a plethora of AEs. Given the mechanism of action, it is supposed that most if not all of them are immune related. Fortunately, the majority are mild and manageable. However, due to the increase in patients' life expectancy, there is a substantial need to understand and prevent severe cutaneous, pulmonary, neurological and other AEs which have major impact on the quality of life. The safety profile after long term use of these medications is still unclear. In addition, non-steroid based immune interventions to control autoimmunity are still to be developed.
Clinical experiences of combining immunotherapy and radiation therapy in non-small cell lung cancer: lessons from melanoma. [2020]Radiation therapy (RT) is an essential component of local control for non-small cell lung cancer (NSCLC), but distant failures dictate the poor prognosis of this disease. Until recently, the possibility of using RT as an immunoadjuvant to stimulate a systemic anti-tumor immune response was not a realistic clinical opportunity. The emergence of immune checkpoint blockade as an effective immunotherapy for NSCLC has opened the door for combinatorial approaches involving RT. In melanoma, the body of preclinical evidence combining radiation and immunotherapy buoyed clinical efforts, from which promising results have begun to emerge. Preclinical work combining radiation and immunotherapy indicate similar findings in NSCLC, and clinical efforts are ongoing. Here, we review the rationale, preclinical evidence, ongoing efforts and anticipated challenges of efforts combining radiation and immunotherapy in NSCLC.
Phase 1 Dose Escalation Trial of Ipilimumab and Stereotactic Body Radiation Therapy in Metastatic Melanoma. [2019]To report the results of a phase 1 trial evaluating the safety of the ipilimumab/radiation therapy combination in patients with metastatic melanoma.
Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab. [2019]The objective of this study was to evaluate the efficacy and safety of concurrent immune checkpoint inhibitor therapy and radiotherapy (immunoradiotherapy) in patients with metastatic melanoma after progression on nivolumab.
Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. [2022]The safety of combined immunotherapy and thoracic radiation therapy (iRT) has been understudied. We evaluated toxicities in patients receiving iRT from 3 single-institutional phase 1/2 trials.
Immunotherapy and radiotherapy in melanoma: a multidisciplinary comprehensive review. [2022]Melanoma is an extremely aggressive tumor and is considered to be an extremely immunogenic tumor because compared to other cancers it usually presents a well-expressed lymphoid infiltration. The aim of this paper is to perform a multidisciplinary comprehensive review of the evidence available about the combination of radiotherapy and immunotherapy for melanoma. Radiation, in fact, can increase tumor antigens visibility and promote priming of T cells but can also exert immunosuppressive action on tumor microenvironment. Combining radiotherapy with immunotherapy provides an opportunity to increase immunostimulatory potential of radiation. We therefore provide the latest clinical evidence about radiobiological rationale, radiotherapy techniques, timing, and role both in advanced and systemic disease (with a special focus on ocular melanoma and brain, liver, and bone metastases) with a particular attention also in geriatric patients. The combination of immunotherapy and radiotherapy seems to be a safe therapeutic option, supported by a clear biological rationale, even though the available data confirm that radiotherapy is employed more for metastatic than for non-metastatic disease. Such a combination shows promising results in terms of survival outcomes; however, further studies, hopefully prospective, are needed to confirm such evidence.
Knowledge About Risks, Benefits, and Curative Potential of Immunotherapy Among Patients with Advanced Cancer. [2021]Immunotherapy is the first-line treatment for melanoma and lung cancer and brings new risks of immune-related adverse events. We aimed to describe patients' knowledge about risks, benefits, and goals of immunotherapy.
Effectiveness and safety of immune checkpoint inhibitors in combination with palliative radiotherapy in advanced melanoma: A systematic review. [2021]Radiotherapy is frequently added to immune checkpoint inhibitors (ICI) when treating melanoma. We sought to describe the efficacy of combination ICI and palliative radiotherapy (pRT) and assess safety, focusing on immune related adverse events (irAE).
Can radiation restore immunotherapy response in metastatic melanoma refractory to checkpoint inhibitors: An institutional experience in salvaging immunotherapy resistant disease. [2023]Melanoma is an immunogenically active tumor with abundantly expressed lymphoid infiltration. Immunotherapy(IO) has proven as a promising treatment option for melanoma but treatment resistance remains as an issue in the majority of patients.There is emerging evidence that radiotherapy (RT) could modulate the tumor microenvironment, increase antigen presentation, and augment adaptive antitumor immunity. Our objective is to evaluate overall treatment response and safety in patients with metastatic melanoma who progressed while on IO, and were treated with RT concurrently with IO for progressive sites.