NBTXR3 + Chemoradiation for Esophageal Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Steven H. Lin, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must be taking: Chemotherapy

Disqualifiers: Metastases, Fistula, Active malignancy, others

No Placebo Group

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}

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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

M D Anderson Cancer Center Houston, TX

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center Lead Sponsor

National Cancer Institute (NCI) Collaborator

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] Esophageal cancer is most frequently treated with platinum-based chemoradiotherapy (CRT). We previously described a phase I study of definitive CRT with docetaxel (DOC) and 5-fluorouracil (5FU) in patients with advanced esophageal cancer. This regimen had low toxicity and was effective without platinating agents. The present study aims to determine the antitumor effects of neoadjuvant CRT with DOC and 5FU and surgical outcomes.

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] Patients with esophageal cancer often develop metastatic disease after esophageal resection and generally receive cisplatin-based chemotherapy or chemoradiotherapy. The efficacy and toxicity of the combination of docetaxel, 5-fluorouracil (5-FU) and cisplatin (DFC) as a second-line chemotherapy were evaluated in patients with postoperative metastatic esophageal cancer refractory to cisplatin-based chemotherapy.

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] This study documents the clinical efficacy and toxicity of S-1 and paclitaxel (S1/PTX) in patients with unresectable or postoperative recurrent esophageal squamous cell carcinoma (ESCC) who had been previously treated with fluorouracil (5FU), cisplatin, and docetaxel.

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] Multiple paclitaxel-based regimens are widely used in chemoradiation therapy against esophageal cancer, including regimens combining paclitaxel with fluorouracil, cisplatin, and carboplatin. However, which among these 3 regimens provides the best prognosis with minimum adverse events is still unknown.

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] We evaluated and compared the efficacy and safety of chemotherapy with paclitaxel plus cisplatin (TP) or carboplatin (TC) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) who underwent neoadjuvant chemoradiotherapy (NCRT).

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] A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC.

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] In esophageal cancer (EC) patients who are not eligible for surgery, definitive chemoradiation (dCRT) with curative intent using cisplatinum with 5-fluorouracil (5-FU) is the standard chemotherapy regimen. Nowadays carboplatin/paclitaxel is also often used. In this study, we compared survival and toxicity rates between both regimens.

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] The docetaxel, 5-fluorouracil, and cisplatin (DCF) regimen is an effective form of chemotherapy for advanced esophageal cancer. However, the incidence of adverse events such as febrile neutropenia and hematological toxicity is high.

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] To evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil as combination chemoradiotherapy (DCF-RT) for cervical esophageal cancer (CEC), we performed a retrospective analysis of CEC patients treated by DCF-RT at a single institution.

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

Phase II Study of Docetaxel, Cisplatin, and 5-Fluorouracil Chemoradiotherapy for Unresectable Esophageal Cancer. [2020] We performed a phase II study of triple-drug combination chemoradiotherapy (DCF-R therapy), in which docetaxel was added to the standard chemoradiotherapy (cisplatin [CDDP]/5-fluorouracil [5-FU]) for unresectable advanced esophageal cancer.

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] There is no standard chemotherapy for esophageal squamous cell carcinoma (ESCC) refractory to first-line fluoropyrimidine- and platinum-based chemotherapy. We therefore performed a randomized, selection-design phase II trial to compare docetaxel (DTX) and paclitaxel (PTX) in this setting.

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] To further improve the prognosis of esophageal cancer patients, it is necessary to investigate new treatment strategies. The purposes of this study were to retrospectively assess the safety and efficacy of neoadjuvant chemoradiotherapy (CRT) with docetaxel/cisplatin/5-fluorouracil (DCF) (DCF-RT) in patients with thoracic esophageal squamous cell carcinoma (ESCC).