NBTXR3 + Radiation Therapy for Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Chemotherapy, Immunotherapy, Targeted therapy

Disqualifiers: Interstitial lung disease, Pneumonitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for non-small cell lung cancer that has recurred and cannot be treated with surgery. It examines how well the drug NBTXR3 (Hafnium Oxide nanoparticles) enhances the effectiveness of radiation therapy in targeting and killing tumor cells while sparing nearby healthy tissue. The trial aims to determine the optimal dose and understand any side effects. Individuals with lung cancer that has returned after radiation and cannot be surgically removed may be suitable candidates. Participants must have a confirmed diagnosis and be unable to undergo surgery for medical reasons. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I need to stop my current medications for this trial?

The trial requires that you stop taking any approved or investigational cancer treatments, like chemotherapy or immunotherapy, at least 3 weeks before starting the trial. However, there might be exceptions for certain medications with short half-lives after discussion with the trial team.

Is there any evidence suggesting that NBTXR3 and radiation therapy are likely to be safe?

Research has shown that NBTXR3, when combined with radiation therapy, has been studied for safety and effectiveness. NBTXR3 acts as a radio-enhancer, improving the ability of radiation to kill cancer cells. Previous patients demonstrated that NBTXR3 can be safely injected into tumors. Studies have focused on determining the right dose and monitoring for serious side effects.

In these studies, NBTXR3 was generally well-tolerated, with most participants not experiencing serious problems. Some side effects occurred, but they were uncommon. The research identified dose-limiting toxicity, where a side effect is severe enough to prevent further dose increases, to find the safest dose.

As this is an early-stage trial, the primary focus is on safety. Current information suggests that NBTXR3 can be used safely with radiation. However, since the trial is still in its early stages, further research is needed to understand its safety in a larger population. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard lung cancer treatments that typically involve radiation therapy alone, NBTXR3 is unique because it combines a new type of nanoparticle with radiation therapy. These nanoparticles are administered directly into the tumor, enhancing the effects of radiation by increasing the damage to cancer cells without affecting surrounding healthy tissue. This targeted approach aims to improve the effectiveness of radiation, potentially leading to better outcomes for patients with fewer side effects. Researchers are excited because this method could significantly boost the precision and potency of lung cancer treatment.

What evidence suggests that NBTXR3 combined with radiation therapy might be an effective treatment for lung cancer?

Research shows that NBTXR3, administered alongside radiation therapy in this trial, can enhance the effectiveness of radiation in killing cancer cells. In earlier studies, NBTXR3 combined with radiation destroyed more cancer cells and controlled tumor growth more effectively than radiation alone. This treatment uses tiny particles to boost the effect of radiation within the tumor while sparing nearby healthy tissues. Early results also indicate that NBTXR3 can strengthen the body's immune response against tumors. Overall, this suggests that using NBTXR3 with radiation could be a promising approach for treating non-small cell lung cancer that cannot be surgically removed or has recurred. ^{1 4 5 6 7}

Who Is on the Research Team?

Saumil Gandhi, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with inoperable, recurrent non-small cell lung cancer who've had radiation therapy over 6 months ago. They must be able to undergo a specific type of injection and have up to 4 treatable lung lesions. Participants need proper organ function and performance status (ECOG 0-2), may have limited additional cancer lesions, and must not be on other systemic cancer therapies or part of another clinical trial.

Inclusion Criteria

My last radiation treatment was over 6 months ago.

I can take care of myself and am up and about more than half of the day.

My doctor says I cannot have surgery for my condition.

Exclusion Criteria

Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

I am using effective birth control methods during the study.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive NBTXR3 intratumorally or intranodally on day 1, followed by radiation therapy 5 times weekly over 3 weeks

3 weeks

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months

Long-term follow-up

Participants are monitored for long-term outcomes and late onset toxicities

3 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• NBTXR3
• Radiation Therapy

Trial Overview The study tests the optimal dose and side effects of NBTXR3 nanoparticles when used with radiation therapy. NBTXR3 aims to enhance the effect of radiotherapy on tumor cells without increasing damage to healthy tissue. The goal is more effective tumor shrinkage while sparing surrounding areas.

How Is the Trial Designed?

Group I: Treatment (NBTXR3, RT) Experimental Treatment 2 Interventions

Patients receive NBTXR3 IT or intranodally on day 1. Within 15 days, patients undergo RT 5 times weekly (Monday-Friday) over 3 weeks for a total of 10-15 fractions.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of NBTXR3, high-dose radiation, low-dose radiation, and immune checkpoint inhibitors significantly improved survival rates in a mouse model of anti-PD1-resistant metastatic lung cancer, increasing survival from 0% to 50%.

This treatment enhanced the immune response by increasing CD8 T-cell infiltration and reducing regulatory T cells in the tumors, suggesting that NBTXR3 may help overcome resistance to anti-PD1 therapy by promoting a stronger antitumor immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model. Hu, Y., Paris, S., Barsoumian, H., et al.[2022]

Stereotactic body radiotherapy (SBRT) is now the standard treatment for patients with non-small cell lung cancer (NSCLC) who cannot undergo surgery, showing promising results, especially when combined with systemic treatments for oligometastatic cases.

Technological advancements in radiotherapy, such as image-guided techniques and the use of proton and carbon ion therapies, have improved the precision of treatment delivery, leading to better patient outcomes and increased overall survival rates in those with inoperable locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current radiotherapy techniques in NSCLC: challenges and potential solutions. Giaj-Levra, N., Borghetti, P., Bruni, A., et al.[2021]

In a study of 55 patients with inoperable non-small cell lung cancer (NSCLC) treated with intensity-modulated radiation therapy (IMRT), the 2-year local control rate was 50% for stage I/II patients and 58% for stage III patients, indicating effective disease management.

The treatment was associated with manageable toxicity, with only 11% of patients experiencing grade 3 acute pulmonary toxicity and no acute treatment-related deaths, suggesting that IMRT is a safe option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy (IMRT) for inoperable non-small cell lung cancer: the Memorial Sloan-Kettering Cancer Center (MSKCC) experience. Sura, S., Gupta, V., Yorke, E., et al.[2022]

In a study of 260 men with localized prostate cancer treated with high-dose IGRT and IMRT, the combination resulted in a low rate of late toxicity, with only 4.4% experiencing grade 2 gastrointestinal issues and 7.1% with grade 2 genitourinary issues after 7 years.

The treatment showed high efficacy, with a 7-year prostate-specific antigen relapse-free survival rate of 97.1% for low-risk patients, indicating that this approach is both safe and effective for managing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Results of IGRT in Prostate Cancer Treatment. Doležel, M., Odrážka, K., Vaňásek, J., et al.[2021]

Image-guided radiation therapy (IGRT) has evolved significantly and is now widely used in routine clinical practice, emphasizing the importance of quality and patient safety in its application across various treatment techniques and anatomical sites.

The American Society for Radiation Oncology recommends a comprehensive quality-assurance program and an interdisciplinary team approach to ensure IGRT is performed safely and effectively, highlighting the need for ongoing updates to practice guidelines as technology advances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. Qi, XS., Albuquerque, K., Bailey, S., et al.[2023]

Concurrent chemoradiation is the standard treatment for locally advanced unresectable non-small-cell lung cancer, highlighting its efficacy as a major therapeutic option.

New radiotherapy techniques, such as respiratory gating and intensity-modulated radiotherapy, are being developed to improve treatment precision, while stereotactic and proton-beam therapies may offer better options for early-stage tumors in non-operable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy for non-small cell lung cancer]. Girard, N., Mornex, F.[2009]

In a study of 120 stage IV non-small cell lung cancer patients treated with immunotherapy, the addition of external beam radiation therapy (EBRT) or radioactive particle implantation (RPI) did not significantly improve overall survival compared to immunotherapy alone, with median survival times of 9 months for IT alone and 10 months for IT with EBRT.

Subgroup analyses indicated that patients receiving RPI had poorer prognoses, particularly in males and those with specific metastases, suggesting that while RT may not enhance survival overall, certain patient characteristics could influence outcomes negatively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy with radiotherapy fails to improve prognosis of patients with stage IV non-small cell lung cancer: a retrospective cohort analysis of the THUNDER-2 study. Liu, L., Yuan, M., Ding, Z., et al.[2023]

In a study involving 18 patients with early-stage central lung tumors, online adaptive intensity modulated proton therapy (IMPT) significantly reduced the mean dose to the bronchial tree compared to MR-guided radiotherapy (MRgRT), suggesting a safer treatment option with lower toxicity risks.

Both non-adaptive and online adaptive IMPT showed significant reductions in the mean doses to the ipsilateral lung and heart compared to MRgRT, indicating improved dose sparing for organs-at-risk during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of MR-guided radiotherapy accumulated doses for central lung tumors with non-adaptive and online adaptive proton therapy. Rabe, M., Palacios, MA., van Sörnsen de Koste, JR., et al.[2023]

In a study involving 15 patients with centrally or superiorly located stage I non-small-cell lung cancer (NSCLC), intensity-modulated proton therapy (IMPT) and passive-scattering proton therapy (PSPT) were found to significantly reduce radiation exposure to surrounding healthy tissues compared to conventional photon stereotactic body radiation therapy (SBRT).

IMPT and PSPT plans not only improved tumor coverage but also minimized the maximum tolerated dose to critical structures like the heart and spinal cord, demonstrating their potential for safer treatment options in patients with challenging tumor locations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton stereotactic body radiation therapy for clinically challenging cases of centrally and superiorly located stage I non-small-cell lung cancer. Register, SP., Zhang, X., Mohan, R., et al.[2021]

In a study of 23 patients with high-risk prostate cancer, stereotactic body radiation therapy (SBRT) was found to be feasible and well tolerated, with low rates of severe gastrointestinal (GI) and genitourinary (GU) toxicities.

The treatment resulted in acute grade 1 GI toxicities in only 9.1% of patients and grade 3 GU toxicities in 4.5%, indicating that serious side effects were uncommon, but further long-term follow-up is needed to assess ongoing safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Tolerance Outcomes of Stereotactic Hypofractionated Accelerated Radiation Therapy Concomitant with Pelvic Node Irradiation in High-risk Prostate Cancer. Pinitpatcharalert, A., Happersett, L., Kollmeier, M., et al.[2022]

Radiation therapy (RT) is crucial for controlling non-small cell lung cancer (NSCLC), but it often fails to prevent distant metastases, leading to poor patient outcomes.

Recent advancements in combining RT with immune checkpoint blockade immunotherapy show promise in enhancing systemic anti-tumor responses in NSCLC, similar to successful strategies seen in melanoma, with ongoing clinical trials exploring this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experiences of combining immunotherapy and radiation therapy in non-small cell lung cancer: lessons from melanoma. Kalbasi, A., Rengan, R.[2020]

Radiotherapy is essential for treating advanced non-small-cell lung cancer (NSCLC), but clinical practices vary widely despite established guidelines.

The introduction of stereotactic ablative radiotherapy (SABR) and immunotherapy has changed treatment strategies, highlighting the need for updated approaches in palliative thoracic radiotherapy for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current landscape of palliative radiotherapy for non-small-cell lung cancer. Jumeau, R., Vilotte, F., Durham, AD., et al.[2020]

Patients with non-small-cell lung cancer treated with proton-beam therapy (PBT) experienced significantly less severe symptoms compared to those treated with intensity-modulated radiation therapy (IMRT) or three-dimensional conformal radiation therapy (3DCRT), indicating a potential advantage of PBT in minimizing treatment-related side effects.

Among the 82 patients studied, pain related to esophagitis increased more during and decreased more after therapy in the IMRT and 3DCRT groups compared to the PBT group, suggesting that PBT may lead to better symptom management and recovery post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Study of Patient-Reported Symptom Burden in Patients With Non-Small-Cell Lung Cancer Undergoing Proton or Photon Chemoradiation Therapy. Wang, XS., Shi, Q., Williams, LA., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9669748/

NBTXR3 improves the efficacy of immunoradiotherapy ... We previously demonstrated that NBTXR3, a nanoparticle radioenhancer, significantly improved immune responses in a murine anti-PD1-resistant metastatic lung ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8052129/

NBTXR3 Radiotherapy-Activated Functionalized Hafnium ... NBTXR3 activated by radiotherapy was also more effective in destroying cancer cells and in controlling tumor growth than radiotherapy alone.

3. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2021.39.3_suppl.66

A new radio-enhancer, PEP503 (NBTXR3), in combination ... Conclusions: Intra-tumor injection of PEP503/NBTXR3 with CCRT is feasible without additional toxicities for rectal cancer patients. The ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04505267

NCT04505267 | NBTXR3 and Radiation Therapy for the ... This phase I trial investigates the best dose and side effects of NBTXR3 when given together with radiation therapy for the treatment of non-small cell lung ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425002246

Radioenhancing hafnium oxide nanoparticles (NBTXR3 ... NBTXR3, a novel radioenhancer, demonstrated enhanced radiotherapy efficacy with minimal toxicity in healthy tissue. We evaluated NBTXR3 ...

6. tandfonline.com tandfonline.com/doi/full/10.2217/nnm-2022-0186

A Phase Ib/II Trial of PEP503 (NBTXR3, Radioenhancer ... This study reveals the protocol of a phase Ib/II study to investigate the safety profile, dose-limiting toxicity and antitumor activity of PEP503 (NBTXR3) ...

7. ir.nanobiotix.com ir.nanobiotix.com/news-releases/news-release-details/nanobiotix-announces-presentation-data-two-phase-1-studies

Release Details NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time ...