NBTXR3 + Radiation Therapy for Pancreatic Cancer

Overseen By Eugene J Koay

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: Gemcitabine, FOLFOX, FOLFIRINOX

Disqualifiers: Prior radiation, Other malignancy, others

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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called NBTXR3 (Hafnium Oxide nanoparticles) used with radiation therapy for people with pancreatic cancer. The goal is to determine the safest dose of NBTXR3 that can be given alongside radiation to help control the cancer. This trial suits those with pancreatic cancer confined to one area (not spread) who have already received a specific chemotherapy treatment. Participants should be able to undergo an injection procedure and have a visible tumor on scans. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

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, it does mention that you should not have received any anti-cancer treatments other than the specified chemotherapies before joining the study.

Is there any evidence suggesting that NBTXR3 is likely to be safe for humans?

Research has shown that NBTXR3 was safe in earlier studies. In one study involving 22 patients with advanced cancers, the treatment was generally well-tolerated. However, 42-47% of patients experienced significant side effects, similar to those seen with other treatments like liver SBRT, a type of radiation therapy. While side effects can occur, they are expected for treatments of this nature. Overall, NBTXR3 appears promising, but participants should discuss potential risks with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NBTXR3 for pancreatic cancer because it offers a unique approach compared to standard treatments like chemotherapy and surgery. NBTXR3 is a novel radio-enhancer that is injected directly into the tumor, which means it specifically targets cancer cells and increases the effectiveness of radiation therapy. This targeted mechanism not only helps to potentially improve outcomes but also minimizes damage to surrounding healthy tissues. This innovative method could bring a new level of precision and efficacy to pancreatic cancer treatment, giving hope for better results in a condition that's notoriously hard to treat.

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

Research has shown that NBTXR3, a new treatment using tiny particles called hafnium oxide nanoparticles, may enhance the effectiveness of radiation therapy. This means it could improve radiation's ability to treat tumors. In this trial, participants will receive NBTXR3 alongside radiation therapy. Earlier studies with patients who had advanced cancers, including pancreatic cancer, found NBTXR3 to be safe and promising. The treatment improved radiation's effectiveness without significantly harming healthy tissue. These early findings suggest that NBTXR3 could be a valuable addition to pancreatic cancer treatment. ^{1 2 3 4}

Who Is on the Research Team?

Eugene J. Koay

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with biopsy-proven pancreatic ductal adenocarcinoma, who've completed a specific chemotherapy regimen without distant metastasis. They must have good performance status, acceptable blood counts and organ function, not be pregnant or breastfeeding, agree to use effective contraception, and have no other active cancers or significant heart disease.

Inclusion Criteria

I am fully active or can carry out light work.

Signed informed consent form (ICF) indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study

I am willing to undergo a special ultrasound-guided injection as my doctor advises.

Exclusion Criteria

I have had surgery to remove a pancreatic tumor.

I have pancreatic cancer and no other active cancers, except for treated and cured skin cancer.

I do not have serious heart rhythm problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive NBTXR3 intratumorally on day 1, followed by 15 fractions of intensity modulated radiation therapy (IMRT) between days 15-43

6 weeks

Multiple visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-ups at 1 month and then every 3 months for up to 1 year

1 year

1 visit (in-person) at 1 month, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• NBTXR3

Trial Overview

The trial is testing the safety and effectiveness of NBTXR3 nanoparticles activated by radiation therapy in treating locally advanced or borderline-resectable pancreatic cancer. It aims to determine the optimal dose of NBTXR3 that can control the disease when combined with radiation.

How Is the Trial Designed?

Group I: Treatment (NBTXR3, radiation therapy) Experimental Treatment 2 Interventions

Patients receive NBTXR3 IT on day 1. Patients then undergo 15 fractions of radiation therapy between days 15-43 in the absence of disease progression or unacceptable toxicity.

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

NBTXR3 nanoparticles can be effectively taken up by various human cancer cell lines, with their uptake and clustering in cells depending on the concentration and type of cancer cells, indicating potential for targeted cancer therapy.

The study suggests that the radioenhancement effect of NBTXR3 nanoparticles can be predicted based on the concentration of nanoparticles and the radiation dose, which could help optimize treatment strategies for different types of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hafnium oxide nanoparticles: toward an in vitro predictive biological effect? Marill, J., Anesary, NM., Zhang, P., et al.[2021]

NBTXR3, a novel radioenhancer made of hafnium oxide nanoparticles, significantly enhances the effectiveness of radiotherapy in treating various solid tumors by improving cancer cell destruction and tumor growth control.

The study demonstrated that NBTXR3 is internalized by cancer cells and remains in tumor tissue during treatment, and it also improves the efficacy of cisplatin-based chemoradiotherapy, suggesting its potential as a universal treatment option for solid cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NBTXR3 Radiotherapy-Activated Functionalized Hafnium Oxide Nanoparticles Show Efficient Antitumor Effects Across a Large Panel of Human Cancer Models. Zhang, P., Marill, J., Darmon, A., et al.[2022]

NBTXR3 nanoparticle injection is a new radioenhancer that shows promise in enhancing the effectiveness of radiation therapy for head and neck squamous cell carcinoma, as observed in CT scans of metastatic lymph nodes.

The injected NBTXR3 material appears hyperattenuating on CT scans, with a mean attenuation of 1516 HU, indicating its presence and potential leakage beyond tumor margins, which may impact treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging Features of Intratumoral Injection of NBTXR3 for Head and Neck Squamous Cell Carcinoma Lymph Node Metastases. Ginat, DT., Juloori, A., Vivar, OI., et al.[2022]

Innovative metal-based anticancer therapies, particularly NBTXR3 nanoparticles, show promise as selective radioenhancers that can enhance the effectiveness of radiotherapy by delivering energy directly to tumor cells, thereby improving cancer treatment outcomes.

NBTXR3 nanoparticles, designed with specific physicochemical properties for efficient uptake by cancer cells, have demonstrated a favorable benefit-risk ratio in non-clinical studies and are currently being tested in clinical trials for advanced soft tissue sarcomas and head and neck cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New use of metals as nanosized radioenhancers. Pottier, A., Borghi, E., Levy, L.[2014]

The phase I study involving 19 elderly or frail patients with advanced head and neck cancer showed that the radioenhancer nanoparticles, NBTXR3, had a good safety profile, with no dose-limiting toxicities or serious adverse events related to the treatment.

NBTXR3 was successfully injected intratumorally and remained localized during radiation therapy, with preliminary signs of antitumor activity observed, indicating its potential for further evaluation in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of NBTXR3 activated by intensity-modulated radiation therapy in elderly patients with locally advanced squamous cell carcinoma of the oral cavity or oropharynx. Hoffmann, C., Calugaru, V., Borcoman, E., et al.[2021]

The first patient with unresectable pancreatic ductal adenocarcinoma (PDAC) treated with NBTXR3 showed no acute adverse events, indicating a promising safety profile for this novel radioenhancer when combined with radiation therapy.

Local endoscopic delivery of NBTXR3 followed by intensity-modulated radiation therapy (IMRT) demonstrated feasibility, with the treatment maintaining tumor stability and no treatment-related toxicity observed during follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NBTXR3, a first-in-class radioenhancer for pancreatic ductal adenocarcinoma: Report of first patient experience. Bagley, AF., Ludmir, EB., Maitra, A., et al.[2023]

In a phase 1 trial involving 13 patients with locally advanced pancreatic cancer, the combination of weekly docetaxel and radiation therapy was found to be feasible and well-tolerated, with a maximum tolerated dose (MTD) established at 35 mg/m2/week.

While the treatment led to some common side effects like nausea and abdominal pain, most toxicities were reversible and did not exceed grade 3, indicating a manageable safety profile despite a significant rehospitalization rate of 28%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and radiotherapy and pancreatic cancer. Viret, F., Ychou, M., Gonçalves, A., et al.[2019]

The newly developed Hafnium Oxide (HfO2) nanoassemblies (NAs) can be injected intravenously, overcoming the limitations of previous HfO2 nanoparticles that required intratumoral injection, thus expanding the range of treatable cancers.

These HfO2 NAs not only enhance the effectiveness of radiation therapy by promoting free-radical generation to kill cancer cells but also demonstrate efficient tumor targeting and are safely cleared from the body, minimizing long-term toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gram-scale synthesis of highly biocompatible and intravenous injectable hafnium oxide nanocrystal with enhanced radiotherapy efficacy for cancer theranostic. Li, Y., Qi, Y., Zhang, H., et al.[2021]

Citations

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Release Details

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NBTXR3, a novel radioenhancer, demonstrated enhanced radiotherapy efficacy with minimal toxicity in healthy tissue. We evaluated NBTXR3 ...

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globenewswire.com/news-release/2025/05/05/3073766/0/en/Nanobiotix-Announces-Full-Results-From-Completed-Phase-1-Study-Evaluating-JNJ-1900-NBTXR3-in-Pancreatic-Cancer.html

Nanobiotix Announces Full Results From Completed Phase 1

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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) ...