Nanoparticle-Enhanced Radiotherapy for Pancreatic Cancer

Recruiting at 2 trial locations

Overseen By Jonathan Leeman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dana-Farber Cancer Institute

Must be taking: Induction chemotherapy

Must not be taking: Antiretrovirals

Disqualifiers: Metastatic disease, Prior radiation, others

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

Compensation: Varies

Number of Visits: 5

Duration: 2 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is being done to help determine the safety and efficacy of gadolinium based nanoparticle, Activation and Guidance of Irradiation X (AGuIX), used in conjunction with MR-guided stereotactic body radiation therapy (SBRT) in the treatment of pancreatic cancer and lung tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on combination antiretroviral therapy for HIV, you would be ineligible due to potential interactions with the study drug.

What data supports the effectiveness of the treatment AGuIX for pancreatic cancer?

AGuIX nanoparticles have shown promise in enhancing the effects of radiation therapy by making cancer cells more sensitive to radiation, as seen in studies with pancreatic cancer cells and other cancer types like brain and lung. These nanoparticles accumulate in tumors and help improve the effectiveness of radiation treatment, potentially leading to better outcomes. ^{1 2 3 4 5}

Is the nanoparticle-enhanced radiotherapy treatment AGuIX safe for humans?

AGuIX nanoparticles have been tested in animals (rodents and monkeys) with no evidence of toxicity, and early human trials have shown no observed toxicity, suggesting they are generally safe for use in humans. ^{2 3 4 6 7}

What makes the treatment AGuIX unique for pancreatic cancer?

AGuIX is unique because it uses gadolinium-based nanoparticles to enhance the effects of radiation therapy by making cancer cells more sensitive to radiation, while also allowing for better imaging of the tumor. This dual function helps target the cancer more precisely and potentially reduces damage to healthy tissues. ^{1 2 3 5 8}

Research Team

Jonathan Leeman, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with certain types of lung or pancreatic cancer that can't be removed by surgery. Participants must have completed standard chemotherapy if they have pancreatic cancer, and their tumors should be no larger than 5cm. They need to have normal organ function, no distant metastasis, and an ECOG performance status ≤2 (which means they are able to walk and do some activities).

Inclusion Criteria

You must have a visible and measurable disease that can be accurately measured.

I can take care of myself but might not be able to do heavy physical work.

My lung cancer has not spread to my lymph nodes and cannot be removed by surgery.

Exclusion Criteria

Participants who are receiving any other investigational agents

You have had allergic reactions to a specific type of contrast dye used for imaging tests.

My cancer has spread to other parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AGuIX nanoparticles and stereotactic body radiation therapy (SBRT) over 5 treatment days

2 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular follow-up visits

Extension

Participants may continue to be monitored for long-term outcomes such as overall survival and quality of life

Up to 100 months

Treatment Details

Interventions

• AGuIX

Trial Overview The study tests a new treatment combining AGuIX nanoparticles with MR-guided stereotactic body radiation therapy (SBRT) for treating non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma. The goal is to see how safe this combination is and how well it works against these cancers.

Participant Groups

Group I: SMART Phase 2 Experimental Treatment 1 Intervention

Randomized participants will receive standard of care SMART, magnetic resonance imaging (MR)-guided stereotactic body radiation therapy (SBRT).

Group II: AGUIX + SMART Phase 2 Experimental Treatment 2 Interventions

Randomized participants will receive recommended phase 1 dose established for their disease group (central lung tumor or locally advanced/unresectable pancreatic ductal adenocarcinoma-LAPC) of Activation and Guidance of Irradiation X (AGUIX) and SMART, magnetic resonance imaging (MR)-guided stereotactic body radiation therapy (SBRT).

Group III: AGUIX + SMART Phase 1 Experimental Treatment 2 Interventions

Dose escalation of Activation and Guidance of Irradiation X (AGUIX) and SMART, magnetic resonance imaging (MR)-guided stereotactic body radiation therapy (SBRT). Central lung tumor cohort will receive: * five fractions of stereotactic body radiation therapy (SBRT) * AGuIX Nanoparticle given on -7 or -14 day prior to radiation treatment, then with 1st fraction of radiation and for patients receiving radiation over a two (2) week period with the 4th fraction of radiation . Locally advanced/unresectable pancreatic ductal adenocarcinoma-LAPC cohort, will receive: five fractions of stereotactic body radiation therapy (SBRT) * AGuIX Nanoparticle given on -7 or -14 day prior to radiation treatment, then with 1st fraction of radiation.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

NH TherAguix SAS

Collaborator

Trials

4

Recruited

350+

Findings from Research

AGuIX nanoparticles, primarily used for MRI imaging, significantly enhance the effectiveness of radiation therapy in pancreatic cancer by decreasing cell survival when combined with X-ray beams rich in low-energy photons.

The optimal concentration of AGuIX in pancreatic cancer cells is reached within 15 minutes, with the nanoparticles mainly localized in the cytoplasm, suggesting a mechanism of action that may involve both physical and chemical processes to improve radiosensitization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AGuIX nanoparticles as a promising platform for image-guided radiation therapy. Detappe, A., Kunjachan, S., Rottmann, J., et al.[2020]

AGuIX® nanoparticles, which are very small and made from a polysiloxane matrix with gadolinium, have shown no toxicity in animal studies, indicating a good safety profile for potential clinical use.

These nanoparticles enhance the effectiveness of radiotherapy by significantly increasing radiosensitivity in various cancer types, including brain and lung cancers, and have successfully progressed to early human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine. Lux, F., Tran, VL., Thomas, E., et al.[2021]

AGuIX nanoparticles, which are gadolinium-based, can enhance the effectiveness of radiation therapy for liver cancer by acting as a radiosensitizer, allowing for lower radiation doses to be used safely.

In studies with HepG2 liver cancer xenografts in nude mice, AGuIX showed significant accumulation in tumors and reduced 18F-FDG uptake after radiation, indicating its potential as a theranostic agent for image-guided radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Novel 64Cu-Labeled Theranostic Gadolinium-Based Nanoprobes in HepG2 Tumor-Bearing Nude Mice. Hu, P., Cheng, D., Huang, T., et al.[2020]

The newly developed AGuIX-Bi nanoparticles, which replace some Gd3+ with Bi3+, enhance radiation dose delivery while maintaining magnetic resonance imaging (MRI) contrast, showing promise for reducing toxicity in cancer treatment.

In a study using a human non-small cell lung cancer model, AGuIX-Bi nanoparticles led to significant tumor growth delay and a 33% complete regression at the optimal Bi/Gd ratio, demonstrating both safety and improved efficacy in combination with radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tuning ultrasmall theranostic nanoparticles for MRI contrast and radiation dose amplification. Brown, N., Rocchi, P., Carmès, L., et al.[2023]

AGuIX nanoparticles (NPs) demonstrated a strong safety profile in rodents, allowing for effective tumor imaging via MRI for up to 24 hours after a single intravenous dose.

When combined with standard 6-MV radiotherapy, AGuIX NPs not only improved tumor visualization but also contributed to a reduction in tumor volume, highlighting their potential as a theranostic tool for brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI-guided clinical 6-MV radiosensitization of glioma using a unique gadolinium-based nanoparticles injection. Verry, C., Dufort, S., Barbier, EL., et al.[2017]

AGuIX nanoparticles, designed for radiosensitization, have shown promising results in preclinical studies and are set to enter a phase I clinical trial, indicating their potential efficacy in enhancing tumor treatment while minimizing damage to healthy tissues.

These nanoparticles not only enhance the effects of radiation therapy but also possess MRI functionality, making them a theranostic option for personalized medicine, which combines therapy and diagnostic imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ultrasmall nanoparticles for radiotherapy: AGuIX]. Lux, F., Detappe, A., Dufort, S., et al.[2015]

AGuIX® is a new gadolinium-based theranostic agent that is well tolerated at high doses and shows ideal biodistribution for both MRI diagnostics and therapeutic applications, rapidly eliminating excess particles through the kidneys.

These nanoparticles act as effective radiosensitizers, enhancing the effects of radiotherapy across various tumor types and conditions, with significant therapeutic effects observed in pre-clinical studies, indicating their potential for improving cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy. Sancey, L., Lux, F., Kotb, S., et al.[2022]

Ultra-small silica-based gadolinium chelated nanoparticles (SiGdNP) enhance radiation therapy by improving tumor cell damage and overall survival in pancreatic tumor models, demonstrating their potential as a dual-function treatment.

SiGdNP were shown to be safely administered systemically and cleared through the kidneys in both cynomolgus monkeys and pancreatic tumor-bearing mice, indicating their suitability for clinical use in MR-guided radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy. Detappe, A., Kunjachan, S., Sancey, L., et al.[2022]

References

1. Austria pubmed.ncbi.nlm.nih.gov

AGuIX nanoparticles as a promising platform for image-guided radiation therapy. [2020]

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

AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine. [2021]

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

Evaluation of Novel 64Cu-Labeled Theranostic Gadolinium-Based Nanoprobes in HepG2 Tumor-Bearing Nude Mice. [2020]

4. Australia pubmed.ncbi.nlm.nih.gov

Tuning ultrasmall theranostic nanoparticles for MRI contrast and radiation dose amplification. [2023]

5. England pubmed.ncbi.nlm.nih.gov

MRI-guided clinical 6-MV radiosensitization of glioma using a unique gadolinium-based nanoparticles injection. [2017]

6. France pubmed.ncbi.nlm.nih.gov

[Ultrasmall nanoparticles for radiotherapy: AGuIX]. [2015]

7. England pubmed.ncbi.nlm.nih.gov

The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy. [2022]