24 Participants Needed

NBTXR3 + Chemoradiation for Esophageal Cancer

Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: M.D. Anderson Cancer Center
Must be taking: Chemotherapy
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

The purpose of this Phase I study is to determine the recommended phase 2 dose (RP2D) and safety profile of NBTXR3 activated by radiation therapy with concurrent chemotherapy for the treatment of patients with esophageal adenocarcinoma. 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 tumor cells and shrink tumors. Chemotherapy drugs, such as oxaliplatin, fluorouracil, capecitabine, docetaxel, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving NBTXR3 activated by radiation therapy with concurrent chemotherapy may help control the disease.

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.

What data supports the effectiveness of the drug NBTXR3 + Chemoradiation for Esophageal Cancer?

Research shows that combinations of drugs like docetaxel and 5-fluorouracil (5-FU) are effective in treating advanced esophageal cancer, with low toxicity. Additionally, paclitaxel-based regimens, often used with carboplatin or cisplatin, are widely used in chemoradiation therapy for esophageal cancer, suggesting potential effectiveness of similar combinations.12345

Is the combination of NBTXR3 and chemoradiation safe for treating esophageal cancer?

The combination of drugs like docetaxel, 5-fluorouracil, and carboplatin, which are part of chemoradiation treatments for esophageal cancer, can have side effects such as febrile neutropenia (fever with low white blood cell count) and other blood-related issues. However, studies suggest that these treatments are generally tolerable, meaning they are safe enough for use under medical supervision.35678

What makes the NBTXR3 + Chemoradiation treatment for esophageal cancer unique?

The NBTXR3 + Chemoradiation treatment is unique because it includes NBTXR3, a novel component made of hafnium oxide nanoparticles, which enhances the effects of radiation therapy, potentially improving the treatment's effectiveness compared to traditional chemoradiotherapy options.39101112

Research Team

Steven H. Lin | MD Anderson Cancer Center

Steven H. Lin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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.
See 16 more

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.
See 11 more

Timeline

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

Treatment Details

Interventions

  • Capecitabine
  • Carboplatin
  • Docetaxel
  • Fluorouracil
  • Leucovorin
  • NBTXR3
  • Paclitaxel
Trial OverviewThe 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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (NBTXR3, IMRT, chemotherapy)Experimental Treatment9 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:

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Approved in European Union as Xeloda for:
  • Colorectal cancer
  • Breast cancer
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Approved in United States as Xeloda for:
  • Colorectal cancer
  • Breast cancer
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Approved in Canada as Xeloda for:
  • Colorectal cancer
  • Breast cancer
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Approved in Japan as Xeloda for:
  • Colorectal cancer
  • Breast cancer

Find a Clinic Near You

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

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.
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]
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.
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.
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]

References

Results of Neoadjuvant Chemoradiotherapy With Docetaxel and 5-Fluorouracil Followed by Esophagectomy to Treat Locally Advanced Esophageal Cancer. [2018]
Second-line combination chemotherapy with docetaxel for cisplatin-pretreated refractory metastatic esophageal cancer: a preliminary report of initial experience. [2018]
A Pilot Trial of S-1 and Paclitaxel in Unresectable or Postoperative Recurrent Esophageal Squamous Cell Carcinoma Pretreated by Fluorouracil, Cisplatin, and Docetaxel Chemotherapy. [2019]
Comparison of 3 Paclitaxel-Based Chemoradiotherapy Regimens for Patients With Locally Advanced Esophageal Squamous Cell Cancer: A Randomized Clinical Trial. [2022]
Safety and efficacy of paclitaxel plus carboplatin versus paclitaxel plus cisplatin in neoadjuvant chemoradiotherapy for patients with locally advanced esophageal carcinoma: a retrospective study. [2023]
Definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) in advanced esophageal cancer: a phase 2 trial (KDOG 0501-P2). [2022]
A comparison of carboplatin and paclitaxel with cisplatinum and 5-fluorouracil in definitive chemoradiation in esophageal cancer patients. [2023]
Risk factors for febrile neutropenia and effectiveness of primary prophylaxis with pegfilgrastim in patients with esophageal cancer treated with docetaxel, cisplatin, and 5-fluorouracil. [2020]
Docetaxel, cisplatin, and 5-fluorouracil combination chemoradiotherapy for patients with cervical esophageal cancer: a single-center retrospective study. [2020]
Phase II Study of Docetaxel, Cisplatin, and 5-Fluorouracil Chemoradiotherapy for Unresectable Esophageal Cancer. [2020]
Randomized phase II study of docetaxel versus paclitaxel in patients with esophageal squamous cell carcinoma refractory to fluoropyrimidine- and platinum-based chemotherapy: OGSG1201. [2021]
Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for locally advanced esophageal squamous cell carcinoma. [2019]