NBTXR3, Chemotherapy, and Radiation Therapy for the Treatment of Esophageal Cancer

NCT04615013 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2020-0122NCI-2020-05329
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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; Gastroesophageal Junction Adenocarcinoma; Pathologic Stage II Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIA Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIB Esophageal Adenocarcinoma AJCC v8; Pathologic Stage III Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIIA Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIIB Esophageal Adenocarcinoma AJCC v8; Thoracic Esophagus Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities (DLTs)

  Will be coded and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5 criteria. Descriptive summary tables will be produced, providing the DLTs by initial planned dose level of NBTXR3, initial planned volume of NBTXR3 to be injected, the injected volume, the radiation therapy dose given and the details of the concurrent chemotherapy given.

  Up to end of treatment visit (day 85)

• Maximum tolerated dose and recommended phase 2 dose (RP2D)

  The Bayesian Optimal Interval design, with accelerated titration, will be used to identify RP2D.

  Up to end of treatment visit (day 85)

Secondary Outcomes (8)

• Incidence of NBTXR3/radiation therapy related late onset toxicities

  From end of treatment visit (day 85) until end of study (1 year)

• Feasibility of NBTXR3 injection in the esophageal tumor and involved regional lymph nodes

  Up to 1 year

• Objective response rate

  Up to 1 year

• Major pathological response rate

  Up to 1 year

• Local progression-free survival

  From NBTXR3 injection to locoregional (i.e., within the esophagus or regional nodes) disease recurrence, local progression confirmed radiographically (RECIST v1.1), or death from any cause, whichever occurs first, assessed up to 1 year

Other Outcomes (11)

• Time-course dependent presence of hafnium in blood and urine following NBTXR3 intratumoral/intranodal injection

  Up to 4 hrs post NBTXR3 injection

• Disease control rate

  At 6 months post NBTXR3

• R-status

  Up to 1 year

Study Arms (1)

Treatment (NBTXR3, IMRT, chemotherapy)

EXPERIMENTAL

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.

Drug: Capecitabine; Drug: Carboplatin; Drug: Docetaxel; Drug: Fluorouracil; Other: Hafnium Oxide-containing Nanoparticles NBTXR3; Radiation: Intensity-Modulated Radiation Therapy; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Paclitaxel

Interventions

Capecitabine DRUG

Not applicable to this study

Also known as: Ro 09-1978/000, Xeloda

Treatment (NBTXR3, IMRT, chemotherapy)

Carboplatin DRUG

Not applicable to this study

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (NBTXR3, IMRT, chemotherapy)

Docetaxel DRUG

Not applicable to this study

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Treatment (NBTXR3, IMRT, chemotherapy)

Fluorouracil DRUG

Not applicable to this study

Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (NBTXR3, IMRT, chemotherapy)

Hafnium Oxide-containing Nanoparticles NBTXR3 OTHER

Given IT or IN

Also known as: NBTXR3

Treatment (NBTXR3, IMRT, chemotherapy)

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMRT

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

Treatment (NBTXR3, IMRT, chemotherapy)

Leucovorin DRUG

Not applicable to this study

Also known as: Folinic acid

Treatment (NBTXR3, IMRT, chemotherapy)

Oxaliplatin DRUG

Not applicable to this study

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Treatment (NBTXR3, IMRT, chemotherapy)

Paclitaxel DRUG

Not applicable to this study

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (NBTXR3, IMRT, chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Interventions

Capecitabine; Carboplatin; Docetaxel; Fluorouracil; dehydroftorafur; Radiotherapy, Intensity-Modulated; Leucovorin; Oxaliplatin; Paclitaxel; Taxes

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Economics; Health Care Economics and Organizations

Study Officials

• Steven H Lin

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: November 4, 2020
• Study Start: November 23, 2020
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)