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

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. ^{1 2 3 4 5}

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. ^{3 5 6 7 8}

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. ^{3 9 10 11 12}

Research Team

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.

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

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 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.

Participant Groups

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+

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.

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]

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 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]

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 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 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]

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 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 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 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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Results of Neoadjuvant Chemoradiotherapy With Docetaxel and 5-Fluorouracil Followed by Esophagectomy to Treat Locally Advanced Esophageal Cancer. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Second-line combination chemotherapy with docetaxel for cisplatin-pretreated refractory metastatic esophageal cancer: a preliminary report of initial experience. [2018]

3. Switzerland 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. [2019]

4. United States 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. [2022]

5. England 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. [2023]

6. United States 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). [2022]

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

A comparison of carboplatin and paclitaxel with cisplatinum and 5-fluorouracil in definitive chemoradiation in esophageal cancer patients. [2023]

8. England 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. [2020]

9. Germany pubmed.ncbi.nlm.nih.gov

Docetaxel, cisplatin, and 5-fluorouracil combination chemoradiotherapy for patients with cervical esophageal cancer: a single-center retrospective study. [2020]

10. Greece pubmed.ncbi.nlm.nih.gov

Phase II Study of Docetaxel, Cisplatin, and 5-Fluorouracil Chemoradiotherapy for Unresectable Esophageal Cancer. [2020]

11. England 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. [2021]

12. Germany pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for locally advanced esophageal squamous cell carcinoma. [2019]