Recruiting
Phase 1

NBTXR3, Chemotherapy, Radiation Therapy

Sponsor:

M.D. Anderson Cancer Center

Code:

NCT04615013

Conditions

Cervical Esophagus Adenocarcinoma

Clinical Stage II Esophageal Adenocarcinoma AJCC v8

Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8

Clinical Stage IIB Esophageal Adenocarcinoma AJCC v8

Clinical Stage III Esophageal Adenocarcinoma AJCC v8

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Capecitabine

Carboplatin

Docetaxel

Fluorouracil

Hafnium Oxide-containing Nanoparticles NBTXR3

Study Details

Brief summary:

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.

Conditions

Cervical Esophagus Adenocarcinoma

Clinical Stage II Esophageal Adenocarcinoma AJCC v8

Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8

Clinical Stage IIB Esophageal Adenocarcinoma AJCC v8

Clinical Stage III Esophageal Adenocarcinoma AJCC v8

Study ID

NCT04615013

Start date

Nov 23, 2020

Status verified date

Jul, 2026

Completion date

Oct 31, 2027

Anticipated

Primary completion date

Oct 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Biopsy proven adenocarcinoma of the cervical or thoracic esophagus or gastroesophageal junction
  • Adenocarcinoma of the esophagus stages II-III allowed
  • Medically able to receive chemoradiation. Following chemotherapy regimens are allowed:

  • Oxaliplatin and fluorouracil (5-FU) or capecitabine
  • Docetaxel and/or 5-FU or paclitaxel
  • Carboplatin and paclitaxel
  • Amenable to undergo the endoscopic ultrasound (EUS) guided injection of NBTXR3 as determined by the investigator or treating physician

  • Patients with lesions for which the EUS scope is not able to traverse the tumor are allowed on this trial as long as an injection can be performed as per treating physician's discretion
  • Has at least 1 and up to 4 target lesion(s) in the esophagus that are measurable on cross sectional imaging and repeated measurements (via Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\] 1.1) at the same anatomical location should be achievable

  • Local nodal disease around the esophagus allowed
  • Nodal target lesions must be >= 15 mm (short axis) based on computed tomography (CT) (slice thickness of 5 mm or less) or magnetic resonance imaging (MRI)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Hemoglobin >= 8.0 g/dL
  • Absolute neutrophil count (ANC) >= 1,500/mm\^3
  • Platelet count >= 100,000/mm\^3
  • Creatinine =< 1.5 x upper limit of normal (ULN)
  • Calculated (Calc.) creatinine clearance > 30 mL/min
  • Glomerular filtration ratio > 40 mL/min per 1.73 m\^2
  • Total bilirubin =< 2.0 mg/dL
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Negative urine or serum pregnancy test =< 7 days of NBTXR3 injection in all female participants of child-bearing potential
  • Signed informed consent form (ICF) indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study

Exclusion Criteria:

  • Prior radiation or any therapy for the treatment of esophageal cancer
  • Prior surgical resection of esophageal tumor
  • Esophageal cancer with radiographic evidence of metastases at screening
  • At screening, past medical history of:

  • Esophageal fistula
  • Tracheoesophageal fistula
  • Siewert type III tumors
  • Evidence of bulky disease and/or abutment of tumor above the carina that may result in tracheoesophageal fistulas as determined by the investigator or treating physician

  • Tumors above the carina without defacement of the fat plane between tumor and the airway are allowed
  • Known uncontrolled (grade >= 2) or active esophageal or gastric ulcer disease within 28 days of enrollment
  • Known contraindication to iodine-based or gadolinium-based intravenous (IV) contrast
  • Active malignancy, in addition to esophageal cancer except for basal cell carcinoma of the skin or non-metastatic low risk prostate cancer definitively treated and relapse free within at least 3 months from time of screening
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, renal failure, cardiac arrhythmia, or psychiatric illness that would limit compliance with treatment
  • Known active, uncontrolled (high viral load) human immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
  • Female patients who are pregnant or breastfeeding
  • Women of child-bearing potential and their male partners who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period. Acceptable methods of contraception are those that, alone or in combination, result in a failure rate of < 1% per year when used consistently and correctly
  • Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

Study Design

Enrollment

24 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (NBTXR3, IMRT, chemotherapy)

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.

Interventions

Capecitabine

Not applicable to this study

Carboplatin

Not applicable to this study

Docetaxel

Not applicable to this study

Fluorouracil

Not applicable to this study

Hafnium Oxide-containing Nanoparticles NBTXR3

Given IT or IN

Intensity-Modulated Radiation Therapy

Undergo IMRT

Leucovorin

Not applicable to this study

Oxaliplatin

Not applicable to this study

Paclitaxel

Not applicable to this study

Primary outcome measure

  • Incidence of dose limiting toxicities (DLTs) [ Time Frame: Up to end of treatment visit (day 85) ]
  • Maximum tolerated dose and recommended phase 2 dose (RP2D) [ Time Frame: Up to end of treatment visit (day 85) ]

Central Contacts and Locations

Locations

M D Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Steven H. Lin

713-606-3836SHLin@mdanderson.org

Principal Investigator:

Steven H. Lin

More Information

Sponsor

M.D. Anderson Cancer Center

Last update posted

Jul 24, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by M.D. Anderson Cancer Center on 2026-07-24.