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Cervical Esophagus AdenocarcinomaPhase 1NCT04615013

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

A Phase 1 study testing Capecitabine, Carboplatin and Docetaxel in people with Cervical Esophagus Adenocarcinoma and Clinical Stage II Esophageal Adenocarcinoma AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record

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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Capecitabine, Carboplatin and Docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
23 Nov 2020to 31 Oct 2027
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Steven H. Lin, 713-606-3836, SHLin@mdanderson.org

    Steven H. Lin

    Recruiting

Other trials in United States

About this study

Official title: A Phase 1 Study of NBTXR3 Activated by Radiotherapy With Concurrent Chemotherapy for Adenocarcinoma of the Esophagus

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the recommended phase II dose (RP2D) of hafnium oxide-containing nanoparticles NBTXR3 (NBTXR3) activated by radiotherapy with concurrent chemotherapy, per standard of care, for treatment naive patients with adenocarcinoma of the esophagus.

SECONDARY OBJECTIVES:

  1. To evaluate the safety and feasibility of radiation with NBTXR3 in patients with adenocarcinoma of the esophagus.

II. To evaluate the anti-tumor response of chemoradiation with NBTXR3 in patients with adenocarcinoma of the esophagus.

III. To evaluate time-to-event outcomes after chemoradiation with NBTXR3 in patients with adenocarcinoma of the esophagus.

EXPLORATORY OBJECTIVES:

  1. To evaluate the body kinetic profile of intratumorally/intranodally injected NBTXR3.

II. To evaluate time to event outcomes for patients with clinical staging of locally advanced, unresectable disease.

III. To evaluate surgical outcomes in patients who undergo surgery after study treatment.

IV. To evaluate radiomic measurements with outcomes. V. To assess immune-related biomarkers of response.

OUTLINE: This is a dose-escalation study of NBTXR3.

Patients receive NBTXR3 intratumorally (IT) or intranodally (IN) on day 1. Beginning day 15, patients undergo intensity-modulated radiation therapy (IMRT) 5 days per week for 6 weeks for a total of 28 fractions in the absence of disease progression or unacceptable toxicity. Beginning on day 15, 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.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Being tested
Capecitabine, Carboplatin, Docetaxel, Fluorouracil, Hafnium Oxide-containing Nanoparticles NBTXR3

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CapecitabineDrug

    Also called Ro 09-1978/000, Xeloda

    Not applicable to this study

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Not applicable to this study

  • DocetaxelDrug

    Also called Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

    Not applicable to this study

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Not applicable to this study

  • Hafnium Oxide-containing Nanoparticles NBTXR3Other

    Also called NBTXR3

    Given IT or IN

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

    Undergo IMRT

  • LeucovorinDrug

    Also called Folinic acid

    Not applicable to this study

  • OxaliplatinDrug

    Also called 1-OHP, Ai Heng, Aiheng, Dacotin

    Not applicable to this study

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Not applicable to this study

Study groups in NCT04615013
Study groupRoleWhat they receive
Treatment (NBTXR3, IMRT, chemotherapy)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to end of treatment visit (day 85)

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

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

    Measured: Up to end of treatment visit (day 85)

Secondary outcomes (8)

  1. Incidence of NBTXR3/radiation therapy related late onset toxicities

    Will be defined as any grade >= 3 adverse event.

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

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

    The feasibility features of NBTXR3 local administration by intratumoral injection will be presented relative to the initial planned volume level in every cohort.

    Measured: Up to 1 year

  3. Objective response rate

    Will be defined as the rate of complete or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, in target and non-target lesions.

    Measured: Up to 1 year

  4. Major pathological response rate

    Will be assessed by the Modified Ryan Scheme for Tumor Regression Score.

    Measured: Up to 1 year

  5. Local progression-free survival

    Will be estimated using the method of Kaplan and Meier. Median times and 95% confidence intervals will also be estimated per dose level.

    Measured: 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

  6. Distant progression-free survival

    Will be estimated using the method of Kaplan and Meier. Median times and 95% confidence intervals will also be estimated per dose level

    Measured: From NBTXR3 injection to the radiographic confirmation (RECIST version 1.1) of a new lesion outside the esophagus and regional nodes, or death from any cause, whichever occurs first, assessed up to 1 year

  7. Progression-free survival

    Will be estimated using the method of Kaplan and Meier. Median times and 95% confidence intervals will also be estimated per dose level.

    Measured: From NBTXR3 injection to local recurrence, local progression, distant progression, confirmed radiographically (RECIST version 1.1), or death from any cause, whichever occurs first, assessed up to 1 year

  8. Overall survival

    Will be estimated using the method of Kaplan and Meier. Median times and 95% confidence intervals will also be estimated per dose level.

    Measured: From NBTXR3 injection to death from any cause or end of study, whichever occurs first, assessed up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2020
  2. Study start23 Nov 2020
  3. Primary completion31 Oct 2027 (estimated)
  4. Study completion31 Oct 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04615013
Sponsor's protocol ID
2020-0122
Other IDs
NCI-2020-05329, 2020-0122
Status last verified
Oct 2026
First submitted
1 Oct 2020
Last updated
7 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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