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

Trial Summary

What is the purpose of this trial?

To find the recommended dose of NBTXR3 that can be given in combination with radiation therapy to patients with pancreatic cancer. To learn if the dose NBTXR3 found in Part 1 can help to control the disease.

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.

What data supports the effectiveness of the treatment NBTXR3 + Radiation Therapy for Pancreatic Cancer?

NBTXR3, a treatment using hafnium oxide nanoparticles, has shown promising results in enhancing the effects of radiation therapy in various cancers like soft tissue sarcoma and head and neck cancer. These nanoparticles help focus the radiation's energy directly on cancer cells, potentially improving treatment outcomes while minimizing damage to healthy tissues. ^{1 2 3 4 5}

Is NBTXR3 safe for use in humans?

NBTXR3, a type of nanoparticle used to enhance radiation therapy, has been tested in various cancers, including head and neck cancer, and has shown to be safe in early studies, even in elderly patients who couldn't undergo standard treatments. ^{1 2 3 6 7}

What makes the treatment NBTXR3 + Radiation Therapy unique for pancreatic cancer?

NBTXR3 is a novel treatment that uses hafnium oxide nanoparticles to enhance the effects of radiation therapy by depositing high amounts of energy directly within cancer cells, making it more effective while minimizing damage to surrounding healthy tissues. ^{1 2 3 4 8}

Research Team

Eugene J. Koay

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

NBTXR3, a first-in-class radioenhancer for pancreatic ductal adenocarcinoma: Report of first patient experience. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Hafnium oxide nanoparticles: toward an in vitro predictive biological effect? [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

NBTXR3 Radiotherapy-Activated Functionalized Hafnium Oxide Nanoparticles Show Efficient Antitumor Effects Across a Large Panel of Human Cancer Models. [2022]

4. Greece pubmed.ncbi.nlm.nih.gov

New use of metals as nanosized radioenhancers. [2014]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Gram-scale synthesis of highly biocompatible and intravenous injectable hafnium oxide nanocrystal with enhanced radiotherapy efficacy for cancer theranostic. [2021]

6. England 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. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Docetaxel and radiotherapy and pancreatic cancer. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Imaging Features of Intratumoral Injection of NBTXR3 for Head and Neck Squamous Cell Carcinoma Lymph Node Metastases. [2022]