NBTXR3 + Chemoradiation for Esophageal Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: Chemotherapy

Disqualifiers: Metastases, Fistula, Active malignancy, others

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

Compensation: Varies

Number of Visits: 8

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 approach for esophageal adenocarcinoma, a type of cancer in the esophagus. The goal is to determine the optimal dose and assess the safety of a drug called NBTXR3, which radiation therapy activates to target and destroy cancer cells. This treatment combines with chemotherapy, such as capecitabine and paclitaxel, to help control the disease. It is intended for individuals with a confirmed diagnosis of stage II or III esophageal adenocarcinoma who are suitable for chemoradiation. Participants should have at least one measurable tumor in the esophagus, as determined by imaging tests. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial involves specific chemotherapy drugs, it's best to discuss your current medications with the trial team to ensure there are no interactions.

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

Research has shown that NBTXR3 is generally safe for people. In a previous study with patients who had advanced esophageal cancer, the treatment did not cause major safety problems. The drug contains tiny particles of hafnium oxide and is injected directly into tumors. When exposed to radiation, these particles can help destroy cancer cells more effectively. The injection process succeeded in 13 patients, demonstrating its feasibility.

The chemotherapy drugs used with NBTXR3 are common in cancer treatment. These include capecitabine, carboplatin, docetaxel, fluorouracil, and paclitaxel. While effective, they can cause side effects like nausea, tiredness, or low blood counts. These side effects are typical for chemotherapy and can usually be managed with medical help.

Overall, while the treatment is still under study, early results suggest it is reasonably safe for participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for esophageal cancer?

Researchers are excited about NBTXR3 for esophageal cancer because it introduces a novel approach by using nanoparticles directly injected into the tumor. Unlike standard chemotherapy and radiation treatments that affect both cancerous and healthy cells, NBTXR3 nanoparticles are designed to enhance the effects of radiation specifically on cancer cells. This targeted method could potentially lead to more effective tumor destruction while minimizing damage to surrounding healthy tissues. The promise of NBTXR3 lies in its ability to make radiation therapy more precise and potent, offering hope for improved outcomes in esophageal cancer treatment.

What evidence suggests that NBTXR3 activated by radiation therapy with concurrent chemotherapy could be effective for esophageal cancer?

Research has shown that NBTXR3, one of the treatments in this trial, may effectively target and destroy cancer cells when combined with radiation therapy. Early findings suggest that patients with esophageal adenocarcinoma tolerate this treatment well. In this trial, the process involves injecting NBTXR3, which contains tiny particles, directly into the tumor. These particles are believed to enhance the effects of radiation therapy, potentially leading to better outcomes. Initial studies in head and neck cancer demonstrated that NBTXR3 could increase the effectiveness of radiotherapy. This promising evidence suggests that NBTXR3 might be a valuable addition to esophageal cancer treatment. ^{1 2 3 6 7}

Who Is on the Research Team?

Steven H. Lin, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with esophageal adenocarcinoma stages II-III who haven't had prior treatments for their cancer. They must have a certain level of blood cells, organ function, and be able to undergo specific diagnostic tests. Pregnant or breastfeeding women can't participate, nor those with other active cancers or serious medical conditions.

Inclusion Criteria

Glomerular filtration ratio > 40 mL/min per 1.73 m^2

Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)

I am considered suitable for a special ultrasound-guided injection as decided by my doctor.

Exclusion Criteria

I do not have severe, active ulcers in my esophagus or stomach.

My esophageal cancer has spread, as shown in scans.

I am allergic to iodine or gadolinium IV contrasts.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NBTXR3 intratumorally or intranodally on day 1, followed by intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy starting on day 15 for 6 weeks

6 weeks

5 visits per week for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

1 year

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Carboplatin
• Docetaxel
• Fluorouracil
• Leucovorin
• NBTXR3
• Paclitaxel

Trial Overview The study is testing NBTXR3 nanoparticles activated by radiation therapy alongside standard chemotherapy drugs (like oxaliplatin and fluorouracil) to see if this combination better controls esophageal cancer compared to current treatments.

How Is the Trial Designed?

Group I: Treatment (NBTXR3, IMRT, chemotherapy) Experimental Treatment 9 Interventions

Patients receive NBTXR3 IT or IN on day 1. Beginning day 15, patients undergo IMRT 5 days per week for 6 weeks for a total of 28 fractions, in the absence of disease progression or unacceptable toxicity. Concurrent with IMRT, patients receive a chemotherapy regimen consisting of either fluorouracil and oxaliplatin with or without leucovorin, oxaliplatin and capecitabine, docetaxel and fluorouracil with or without leucovorin, docetaxel and paclitaxel, or carboplatin and paclitaxel per physician discretion.

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

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

Neoadjuvant chemoradiotherapy (CRT) with docetaxel/cisplatin/5-fluorouracil (DCF) was found to be safe and effective in treating 30 patients with thoracic esophageal squamous cell carcinoma (ESCC), with a high pathological complete response (pCR) rate of 57% in primary tumors.

The treatment significantly reduced lymph node metastases and resulted in a 3-year overall survival rate of 62.2%, which increased to 84% for patients who achieved pCR, suggesting a potential survival benefit from this neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for locally advanced esophageal squamous cell carcinoma. Sasaki, K., Uchikado, Y., Omoto, I., et al.[2019]

In a study of 201 patients with locally advanced esophageal squamous cell carcinoma, the chemotherapy regimen of carboplatin plus paclitaxel (TP) resulted in significantly higher rates of severe adverse events compared to carboplatin plus cisplatin (TC), particularly with a higher incidence of grade 3 or higher febrile neutropenia.

Despite the differences in safety, both TP and TC regimens showed comparable overall survival and progression-free survival rates, suggesting that TC is the preferred option due to its better safety profile without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of paclitaxel plus carboplatin versus paclitaxel plus cisplatin in neoadjuvant chemoradiotherapy for patients with locally advanced esophageal carcinoma: a retrospective study. Jiang, L., Zhu, J., Chen, X., et al.[2023]

In a study of 38 patients with locally advanced esophageal cancer, neoadjuvant chemoradiotherapy (CRT) using docetaxel and 5-fluorouracil showed low toxicity, with esophagitis being the most common side effect (26.3% grade 3), and no postoperative mortality reported.

The treatment resulted in favorable surgical outcomes, with 92.1% of patients achieving complete resection and a 5-year overall survival rate of 44.7%, indicating that this regimen is a promising alternative for patients who cannot tolerate traditional platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of Neoadjuvant Chemoradiotherapy With Docetaxel and 5-Fluorouracil Followed by Esophagectomy to Treat Locally Advanced Esophageal Cancer. Hamai, Y., Hihara, J., Emi, M., et al.[2018]

In a phase II study involving 61 patients with unresectable advanced esophageal cancer, the triple-drug combination chemoradiotherapy (DCF-R therapy) showed a high response rate of 85.2% for the main tumor and significant effectiveness against metastases.

The treatment was well-tolerated, with a 90.2% completion rate and no treatment-related deaths, while median survival time was 406 days, indicating both efficacy and safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Docetaxel, Cisplatin, and 5-Fluorouracil Chemoradiotherapy for Unresectable Esophageal Cancer. Takahashi, K., Osaka, Y., Ota, Y., et al.[2020]

In a study of 21 patients with cervical esophageal cancer treated with a combination of docetaxel, cisplatin, and 5-fluorouracil (DCF-RT), the treatment resulted in a high overall complete response rate of 61.9% and a local complete response rate of 81.0%.

The 3-year overall survival rate was 79.6%, indicating that DCF-RT is an effective treatment option for cervical esophageal cancer, although it is associated with significant myelosuppression, requiring careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel, cisplatin, and 5-fluorouracil combination chemoradiotherapy for patients with cervical esophageal cancer: a single-center retrospective study. Sakai, M., Sohda, M., Saito, H., et al.[2020]

In a study of 92 patients with esophageal cancer treated with the DCF chemotherapy regimen, the use of pegfilgrastim significantly reduced the incidence of febrile neutropenia from 32.2% to 3.0%, highlighting its efficacy as a primary prophylaxis.

Patients receiving pegfilgrastim also experienced fewer severe adverse effects (12.1% vs 69.5%) and had a lower rate of treatment interruptions, indicating that pegfilgrastim not only enhances safety but also supports the continuation of effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for febrile neutropenia and effectiveness of primary prophylaxis with pegfilgrastim in patients with esophageal cancer treated with docetaxel, cisplatin, and 5-fluorouracil. Ohkura, Y., Ueno, M., Udagawa, H.[2020]

In a study of 102 esophageal cancer patients, both cisplatinum/5-FU and carboplatin/paclitaxel regimens showed similar overall survival and disease-free survival rates, indicating that carboplatin/paclitaxel is a viable alternative to the standard cisplatinum/5-FU treatment.

Carboplatin/paclitaxel demonstrated significantly lower toxicity rates and higher treatment completion rates compared to cisplatinum/5-FU, suggesting it may be a safer option for patients not eligible for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of carboplatin and paclitaxel with cisplatinum and 5-fluorouracil in definitive chemoradiation in esophageal cancer patients. Honing, J., Smit, JK., Muijs, CT., et al.[2023]

The combination of docetaxel, 5-fluorouracil, and cisplatin (DFC) shows promise as a second-line chemotherapy for patients with metastatic esophageal cancer who are resistant to cisplatin, with a median overall survival of 8 months based on a study of 20 patients.

While DFC treatment resulted in a complete response in 1 patient and partial responses in 6 others, it also led to significant myelosuppression, with 65% of patients experiencing severe neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line combination chemotherapy with docetaxel for cisplatin-pretreated refractory metastatic esophageal cancer: a preliminary report of initial experience. Tanaka, T., Fujita, H., Sueyoshi, S., et al.[2018]

In a study of 28 patients with unresectable or recurrent esophageal squamous cell carcinoma (ESCC), the combination of S-1 and paclitaxel (S1/PTX) showed a response rate of 14.8%, with a median overall survival time of 306 days, indicating some clinical efficacy in this difficult-to-treat population.

While S1/PTX was generally well-tolerated, severe neutropenia occurred in 13 patients, highlighting the need for monitoring blood counts during treatment, although most non-hematological side effects were mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Trial of S-1 and Paclitaxel in Unresectable or Postoperative Recurrent Esophageal Squamous Cell Carcinoma Pretreated by Fluorouracil, Cisplatin, and Docetaxel Chemotherapy. Nakajima, Y., Kawada, K., Tokairin, Y., et al.[2019]

In a phase II trial involving 78 patients with esophageal squamous cell carcinoma who did not respond to first-line chemotherapy, paclitaxel (PTX) significantly improved overall survival (8.8 months) compared to docetaxel (DTX) (7.3 months).

PTX also demonstrated better progression-free survival (4.4 months vs. 2.1 months) and a higher response rate (25.6% vs. 7.7%), while having a more manageable safety profile with fewer severe side effects compared to DTX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of docetaxel versus paclitaxel in patients with esophageal squamous cell carcinoma refractory to fluoropyrimidine- and platinum-based chemotherapy: OGSG1201. Yamamoto, S., Kawakami, H., Kii, T., et al.[2021]

In a phase 2 study involving 42 patients with advanced esophageal cancer, the combination of docetaxel, cisplatin, and 5-fluorouracil (DCF-R) showed a clinical complete response rate of 52.4%, indicating significant efficacy in treating this condition.

While DCF-R was effective, it also led to considerable side effects, including high rates of leukopenia and neutropenia, suggesting that while the treatment is promising, careful monitoring for these toxicities is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) in advanced esophageal cancer: a phase 2 trial (KDOG 0501-P2). Higuchi, K., Komori, S., Tanabe, S., et al.[2022]

In a randomized clinical trial involving 321 patients with esophageal squamous cell carcinoma (ESCC), the overall survival rates after 3 years were similar across three treatment regimens: paclitaxel with fluorouracil (57.2%), cisplatin (60.1%), and carboplatin (56.5%), indicating no significant superiority of one regimen over the others.

The cisplatin regimen was associated with significantly higher rates of severe side effects, including neutropenia (60.8%), thrombocytopenia (13.1%), and gastrointestinal issues, compared to the fluorouracil and carboplatin groups, suggesting that while all regimens are effective, cisplatin may pose greater risks for adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of 3 Paclitaxel-Based Chemoradiotherapy Regimens for Patients With Locally Advanced Esophageal Squamous Cell Cancer: A Randomized Clinical Trial. Ai, D., Ye, J., Wei, S., et al.[2022]

Citations

1. ir.nanobiotix.com ir.nanobiotix.com/news-releases/news-release-details/nanobiotix-announces-first-data-phase-1-study-evaluating-jnj

NANOBIOTIX Announces First Data From Phase 1 Study ... Treatment was well-tolerated and injection feasibility was confirmed in 13 patients with locally advanced adenocarcinoma of the esophagus ...

2. finance.yahoo.com finance.yahoo.com/news/nanobiotix-announces-first-data-phase-201500275.html

NANOBIOTIX Announces First Data From Phase 1 Study ... Treatment was well-tolerated and injection feasibility was confirmed in 13 patients with locally advanced adenocarcinoma of the esophagus.

3. ecan.org ecan.org/2025/10/02/nbtxr3/

Possible New Weapon to Fight Esophageal Cancer ... This approach works by injecting the tumor with NBTXR3 (hafnium oxide-containing nanoparticles), believed to cause targeted destruction of ...

4. targetedonc.com targetedonc.com/view/nbtxr3-well-tolerated-in-r-m-hnscc-with-early-efficacy-signals

NBTXR3 Well Tolerated in R/M HNSCC, With Early Efficacy ... Innovative NBTXR3 shows promise in enhancing radiotherapy for recurrent head and neck cancer, potentially transforming treatment options for ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02468-1/fulltext

489P Analysis of 3-dimensional volumetric distribution and ... Tumor responses were observed indicating the potential for NBTXR3 to improve patient outcomes at the doses tested and with dispersion within the tumor of up to ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-05329

NBTXR3, Chemotherapy, and Radiation Therapy for the ... NBTXR3 is a drug that when activated by radiation therapy, may cause targeted destruction of cancer cells. Radiation therapy uses high energy x-rays to kill ...

7. marketchameleon.com marketchameleon.com/articles/b/2025/10/2/early-nbtxr3-trial-data-esophageal-cancer-85-percent-disease-control

Early NBTXR3 Trial Data in Esophageal Cancer Show 85 ... Early NBTXR3 Trial Data in Esophageal Cancer Show 85% Disease Control Rate and Feasible Injection Approach · Study Finds High Response Rates and ...