NBTXR3 + Radiation and Immunotherapy for Metastatic Lung Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must not be taking: Immunosuppressants, Corticosteroids
Disqualifiers: CNS metastases, Autoimmune disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This phase I/II trial studies the side effects and possible benefits of NBTXR3, radiation therapy, Anti PD-1 / PD-L1 in treating patients with solid tumor that has spread to the lung (lung metastases) and/or liver (liver metastases). NBTXR3 may help make tumor cells more sensitive to the radiation therapy. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with Anti PD-1 / PD-L1 monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving NBTXR3, radiation therapy, Anti PD-1 / PD-L1 may help to control the disease.
Do I need to stop my current medications for this trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received any anti-cancer treatments, except for anti-PD-1/L1 therapy, within 2 weeks before the NBTXR3 injection. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the treatment NBTXR3 + Radiation and Immunotherapy for Metastatic Lung Cancer?
Research shows that combining NBTXR3, a nanoparticle that enhances radiation effects, with radiation and immunotherapy can improve survival and create long-term immune memory in lung cancer models. Additionally, combining immunotherapy drugs like nivolumab with radiation has shown improved outcomes in lung cancer patients.
12345What makes the NBTXR3 + Radiation and Immunotherapy treatment unique for metastatic lung cancer?
This treatment is unique because it combines NBTXR3, a nanoparticle that enhances the effects of radiation, with immunotherapy to improve the immune response against tumors, even in cases resistant to PD-1 inhibitors. This approach not only targets the primary tumor with high-dose radiation but also uses low-dose radiation on secondary tumors, potentially leading to long-term immune memory against cancer.
25678Eligibility Criteria
Adults with advanced solid tumors that have spread to the lungs or liver may join this trial. They should have tried anti-PD-1/L1 therapy before, be in a decent physical state (ECOG 0-2), and not be pregnant or breastfeeding. Participants need functioning major organs and can't have had certain recent treatments or live vaccines, active infections, severe heart conditions, psychiatric illnesses, or specific allergies.Inclusion Criteria
I have had one previous treatment with an anti-PD-1 or PD-L1 therapy.
I have received a specific high dose radiation treatment.
My cancer has spread to my lung, liver, or soft tissue and cannot be cured with surgery or radiation.
+10 more
Exclusion Criteria
I am not pregnant or breastfeeding.
I have been treated for an autoimmune disease in the last 2 years.
My targeted lesion has been treated with high-dose radiation before.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Patients receive NBTXR3 intratumorally on day 1, followed by Anti PD-1/L-1 intravenously on day 8. Radiation therapy (Abscopal or RadScopal) begins on day 15 and lasts 1-2 weeks. Cycles with Anti PD-1/L-1 repeat every 3-6 weeks up to 2 years.
Up to 2 years
Follow-up
Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 12 weeks for up to 2 years post-radiation therapy.
Up to 2 years
Participant Groups
The study is testing NBTXR3 nanoparticles activated by radiation along with immunotherapy drugs against cancer that has spread to the lung/liver. It aims to see if making tumor cells more sensitive to radiation improves treatment outcomes when combined with immune system-boosting drugs.
2Treatment groups
Experimental Treatment
Group I: Cohort II (NBTXR3, RadScopal, Anti PD-1 / PD-L1Experimental Treatment2 Interventions
COHORT II: Patients receive NBTXR3 intratumorally on day 1. Patients also receive ( anti-PD-1/L-1) IV on day 8. Beginning day 15, patients undergo RadScopal radiation therapy over 1-2 weeks. Cycles with ( anti-PD-1/L-1)repeat every 3-6 weeks per standard of care up to 2 years in the absence of disease progression or unacceptable toxicity.
Group II: Cohort I (NBTXR3, Abscopal, Anti PD-1 / PD-L1Experimental Treatment2 Interventions
COHORT I: Patients receive NBTXR3 intratumorally on day 1. Patients also receive ( anti-PD-1/L-1) intravenously (IV) on day 8. Beginning day 15, patients undergo Abscopal radiation therapy over 1-2 weeks. Cycles with ( anti-PD-1/L-1) repeat every 3-6 weeks per standard of care up to 2 years 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:
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
NBTXR3 Radiotherapy-Activated Functionalized Hafnium Oxide Nanoparticles Show Efficient Antitumor Effects Across a Large Panel of Human Cancer Models. [2022]The side effects of radiotherapy induced on healthy tissue limit its use. To overcome this issue and fully exploit the potential of radiotherapy to treat cancers, the first-in-class radioenhancer NBTXR3 (functionalized hafnium oxide nanoparticles) has been designed to amplify the effects of radiotherapy.
A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model. [2022]Combining radiotherapy with PD1 blockade has had impressive antitumor effects in preclinical models of metastatic lung cancer, although anti-PD1 resistance remains problematic. Here, we report results from a triple-combination therapy in which NBTXR3, a clinically approved nanoparticle radioenhancer, is combined with high-dose radiation (HDXRT) to a primary tumor plus low-dose radiation (LDXRT) to a secondary tumor along with checkpoint blockade in a mouse model of anti-PD1-resistant metastatic lung cancer.
Prospective Single-Arm Phase 1 and 2 Study: Ipilimumab and Nivolumab With Thoracic Radiation Therapy After Platinum Chemotherapy in Extensive-Stage Small Cell Lung Cancer. [2022]Consolidative thoracic radiation therapy (TRT) has been shown to improve outcomes for patients with extensive stage small cell lung cancer. We hypothesized that the addition of ipilimumab (IPI) and nivolumab (NIVO) after TRT would improve outcomes for patients with extensive stage small cell lung cancer.
Hafnium oxide nanoparticles: toward an in vitro predictive biological effect? [2021]Hafnium oxide, NBTXR3 nanoparticles were designed for high dose energy deposition within cancer cells when exposed to ionizing radiation. The purpose of this study was to assess the possibility of predicting in vitro the biological effect of NBTXR3 nanoparticles when exposed to ionizing radiation.
Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial. [2020]Hypofractionated palliative radiotherapy for metastatic lung cancer patients is frequently used in order to ease pain, to increase bone stability, to treat local mass effects, or to prolong progression-free survival at critical sites. Recently introduced, immunotherapy for patients with non-squamous non-small cell lung carcinoma (NSCLC) has significantly improved outcome in this cohort. Preclinical and early clinical data suggest that the combination of photon radiation with programmed death-1 (PD-1) targeting immunotherapies may promote a strong and durable immune response against tumor manifestations both within and beyond radiation targets.
[Combination of Radiation Therapy and Immunotherapy for Non-small Cell Lung Cancer: Peer Exchange on Frontier Academic Topics]. [2021]Lung cancer is the leading cause of cancer death worldwide as well as in China. For many years, conventional oncologic treatments such as surgery, chemotherapy, and radiotherapy (RT) have dominated the field of non-small cell lung cancer (NSCLC). The recent introduction of immunotherapy in clinical practice, led to a paradigm shift in lung cancer as in many other solid tumors. Recent pre-clinical and clinical data have shown RT may also modify antitumor immune responses through induction of immunogenic cell death and reprogramming of the tumor microenvironment. This has led many to reexamine RT as a partner therapy to immuno-oncology treatments and investigate their potential synergy in an exponentially growing number of clinical trials. Clinical trials combining radiotherapy and immunotherapy are attracting major attention, experts were invited to discuss frontier and controversial academic topics: (1) Recent developments of clinical synergy between radiation and immune checkpoint inhibitors (ICIs) in the treatment of NSCLC; (2) Will immunotherapy and radiotherapy increase the toxicity risk for cancer patients; (3) How to cope the mixed responses/disassociated responses phenomenon in checkpoint inhibition therapy to NSCLC with local ablative therapy; (4) Combining radiotherapy and immunotherapy in the treatment of NSCLC brain metastases.
Imaging Features of Intratumoral Injection of NBTXR3 for Head and Neck Squamous Cell Carcinoma Lymph Node Metastases. [2022]NBTXR3 nanoparticle injection is a relatively novel radioenhancer for treatment of various cancers. CT scans following NBTXR3 injection of metastatic lymph nodes from head and neck squamous cell carcinoma were reviewed in a small series of patients. The radioenhancing appears as hyperattenuating, with a mean attenuation of the injected material of 1516 HU. The material was found to leak beyond the margins of the tumor in some cases.
NBTXR3 improves the efficacy of immunoradiotherapy combining nonfucosylated anti-CTLA4 in an anti-PD1 resistant lung cancer model. [2022]The efficacy of immunoradiotherapy consisting of radiation therapy and immune checkpoint blockade relies on effectively promoting the systemic antitumor immune response's activation while simultaneously reducing local factors favoring immune suppression. We previously demonstrated that NBTXR3, a nanoparticle radioenhancer, significantly improved immune responses in a murine anti-PD1-resistant metastatic lung cancer model. We hypothesize that radioactivated-NBTXR3 addition to anti-PD1 and a second-generation anti-CTLA4 could improve treatment effectiveness. To test this hypothesis, we inoculated mice with 344SQR cells in the right and left legs to establish primary and secondary tumors. The primary tumors were intratumorally injected with NBTXR3 nanoparticles on day 7, followed by three fractions of 12 Gy radiation on days 8, 9, and 10. The secondary tumors received two fractions of 1Gy radiation on days 13 and 14. Multiple rounds of anti-PD1, anti-CTLA4 or nonfucosylated anti-CTLA4 were given to the mice. Immune profiling of the tumors revealed that the combination of NBTXR3 with immunoradiotherapy significantly upregulated the activities of a wide range of antitumor immune pathways and reduced the abundance of regulatory suppressor T cells. This combination effectively eradicated the primary and secondary tumors and increased animal survival to 75%. Remarkably, previously treated with NBTXR3-containing treatment, the survivor mice exhibited a long-lasting antitumor memory immune response. This data provides compelling evidence of the efficacy of NBTXR3 to synergize with the immunoradiotherapy approach when combined with an anti-PD1 and multiple checkpoints such as a second generation anti-CTLA4 and show the potential for clinical uses of antitumor immunomodulatory effects of NBTXR3.