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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for pancreatic cancer and certain lung tumors using a special nanoparticle called AGuIX. The researchers aim to determine if this nanoparticle, combined with a precise form of radiation therapy, is safe and effective. People with confirmed pancreatic cancer or specific lung tumors that cannot be surgically removed might be suitable candidates. Participants will receive a combination of the nanoparticle and radiation therapy to evaluate its effectiveness against the tumors. As a Phase 1 and Phase 2 trial, this study focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group, offering participants the opportunity to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AGuIX, a gadolinium-based particle, is being tested for safety with MR-guided stereotactic body radiation therapy (SBRT). This research focuses on treating pancreatic cancer and lung tumors.

In past studies, patients generally tolerated AGuIX well. Researchers closely monitored side effects, with common ones including mild tiredness and skin reactions, typical of radiation treatments. Serious side effects were rare, though they can occur with any treatment.

The current trial phase indicates that AGuIX has passed initial safety tests, having been tried in smaller groups without major issues. This is promising for potential trial participants. However, individual experiences may vary, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Most treatments for pancreatic cancer, like chemotherapy and radiation, attack cancer cells but also harm healthy ones. But AGuIX, a novel nanoparticle, works differently. It enhances the effects of radiation therapy by specifically targeting cancer cells, potentially making the treatment more precise and effective. This means less damage to healthy tissue and possibly fewer side effects. Researchers are excited about AGuIX because it could make radiation therapy smarter and more efficient, offering new hope for patients with difficult-to-treat pancreatic cancer.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research shows that AGuIX, a special nanoparticle containing gadolinium, may enhance the effectiveness of radiation therapy. In earlier studies, patients with tumors who received both AGuIX and radiation therapy experienced better targeting of cancer cells. AGuIX directs the radiation more precisely to the tumor, potentially leading to improved outcomes. In this trial, some participants will receive AGuIX with stereotactic body radiation therapy (SBRT) to assess its effectiveness in treating pancreatic cancer and lung tumors. Other participants will receive standard SBRT without AGuIX. Early evidence suggests that combining AGuIX with SBRT might be more effective, but further research is needed to confirm these findings. ^{1 2 3 4 6}

Who Is on the Research Team?

Jonathan Leeman, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 (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, 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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04789486

NCT04789486 | Nano-SMART: Nanoparticles With MR ... This research study is being done to help determine the safety and efficacy of gadolinium based nanoparticle, Activation and Guidance of Irradiation X ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-06084

Stereotactic Magnetic Resonance-Guided Adaptive ... This Phase I/II trial is to find the side effects and best dose of irradiation X polysiloxane/gadolinium chelates-based nanoparticles (AGuIX) in combination ...

3. dana-farber.org dana-farber.org/clinical-trials/19-826

Nano-SMART: An adaptive phase I-II trial of AGuIX ... This research study is being done to help determine the safety and efficacy of gadolinium based nanoparticle, Activation and Guidance of Irradiation X (AGuIX),

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04789486?term=nanoparticles&cond=%20Lung%20%20cancer&viewType=Table&rank=3

Nano-SMART: Nanoparticles With MR Guided SBRT in ... This research study is being done to help determine the safety and efficacy of gadolinium based nanoparticle , Activation and Guidance of Irradiation X ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006295224006865

Breakthroughs in nanoparticle-based strategies for ... Thivat et al., discussed a large phase I and II clinical study (NCT04881032) on the use of metal NPs, specifically AGuIX (activation and guidance of irradiation ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10105392/

Phase I/II study testing the combination of AGuIX ... The aim of this study is to determine the recommended dose of AGuIX as a radiosensitizer in combination with radiotherapy and TMZ during the concurrent radio- ...