- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04615013
NBTXR3, Chemotherapy, and Radiation Therapy for the Treatment of Esophageal Cancer
A Phase 1 Study of NBTXR3 Activated by Radiotherapy With Concurrent Chemotherapy for Adenocarcinoma of the Esophagus
Study Overview
Status
Conditions
- Gastroesophageal Junction Adenocarcinoma
- Clinical Stage II Esophageal Adenocarcinoma AJCC v8
- Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8
- Clinical Stage III Esophageal Adenocarcinoma AJCC v8
- 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
- Clinical Stage IIB Esophageal Adenocarcinoma AJCC v8
- Cervical Esophagus Adenocarcinoma
- Thoracic Esophagus Adenocarcinoma
Detailed Description
PRIMARY OBJECTIVE:
I. 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:
I. 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:
I. 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.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- M D Anderson Cancer Center
-
Contact:
- Steven H. Lin
- Phone Number: 713-606-3836
- Email: SHLin@mdanderson.org
-
Principal Investigator:
- Steven H. Lin
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Undergo IMRT
Other Names:
Not applicable to this study
Other Names:
Not applicable to this study
Other Names:
Not applicable to this study
Other Names:
Not applicable to this study
Other Names:
Given IT or IN
Other Names:
Not applicable to this study
Other Names:
Not applicable to this study
Other Names:
Not applicable to this study
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of dose limiting toxicities (DLTs)
Time Frame: Up to end of treatment visit (day 85)
|
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)
Time Frame: Up to end of treatment visit (day 85)
|
The Bayesian Optimal Interval design, with accelerated titration, will be used to identify RP2D.
|
Up to end of treatment visit (day 85)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of NBTXR3/radiation therapy related late onset toxicities
Time Frame: From end of treatment visit (day 85) until end of study (1 year)
|
Will be defined as any grade >= 3 adverse event.
|
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
Time Frame: Up to 1 year
|
The feasibility features of NBTXR3 local administration by intratumoral injection will be presented relative to the initial planned volume level in every cohort.
|
Up to 1 year
|
Objective response rate
Time Frame: Up to 1 year
|
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.
|
Up to 1 year
|
Major pathological response rate
Time Frame: Up to 1 year
|
Will be assessed by the Modified Ryan Scheme for Tumor Regression Score.
|
Up to 1 year
|
Local progression-free survival
Time Frame: 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
|
Will be estimated using the method of Kaplan and Meier.
Median times and 95% confidence intervals will also be estimated per dose level.
|
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
|
Distant progression-free survival
Time Frame: 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
|
Will be estimated using the method of Kaplan and Meier.
Median times and 95% confidence intervals will also be estimated per dose level
|
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
|
Progression-free survival
Time Frame: 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
|
Will be estimated using the method of Kaplan and Meier.
Median times and 95% confidence intervals will also be estimated per dose level.
|
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
|
Overall survival
Time Frame: From NBTXR3 injection to death from any cause or end of study, whichever occurs first, assessed up to 1 year
|
Will be estimated using the method of Kaplan and Meier.
Median times and 95% confidence intervals will also be estimated per dose level.
|
From NBTXR3 injection to death from any cause or end of study, whichever occurs first, assessed up to 1 year
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time-course dependent presence of hafnium in blood and urine following NBTXR3 intratumoral/intranodal injection
Time Frame: Up to 4 hrs post NBTXR3 injection
|
Up to 4 hrs post NBTXR3 injection
|
|
Disease control rate
Time Frame: At 6 months post NBTXR3
|
Will be defined as the proportion of patients without progression (local or distant) 6-months post NBTXR3 injection.
|
At 6 months post NBTXR3
|
R-status
Time Frame: Up to 1 year
|
Will be assessed macroscopically by surgeon.
|
Up to 1 year
|
Pathological response rate
Time Frame: Up to 1 year
|
Will be assessed by the Modified Ryan Scheme for Tumor Regression Score.
|
Up to 1 year
|
Prognosis of patients with baseline and follow-up quantitative computed tomography image-based analysis
Time Frame: Up to 1 year
|
Up to 1 year
|
|
Changes in radiomic measurements
Time Frame: Baseline up to 1 year
|
Will evaluate clinical and pathological outcomes of patients with changes in radiographic features.
|
Baseline up to 1 year
|
Tumor microenvironment
Time Frame: Up to time of surgery or up to 141 days after end of treatment visit (for patients not undergoing surgery)
|
Will analyze the tumor microenvironment through multiplexed immunohistochemistry (mIHC).
|
Up to time of surgery or up to 141 days after end of treatment visit (for patients not undergoing surgery)
|
Ribonucleic acid expression
Time Frame: Up to time of surgery or up to 141 days after end of treatment visit (for patients not undergoing surgery)
|
Up to time of surgery or up to 141 days after end of treatment visit (for patients not undergoing surgery)
|
|
Cytokine profiling
Time Frame: Up to 1 year
|
Up to 1 year
|
|
Immune activation quantification
Time Frame: Up to 1 year
|
Will quantify immune activation by analyzing T and B cells, peripheral blood mononuclear cells using flow cytometry, and esophageal cancer biopsies using mIHC.
|
Up to 1 year
|
Concordance of cell free deoxyribonucleic acid (DNA)
Time Frame: Up to 1 year
|
Will evaluate the concordance of cell free DNA detected mutations to those detected in esophageal cancer tumor-derived DNA.
|
Up to 1 year
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Steven H Lin, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Esophageal Diseases
- Adenocarcinoma
- Esophageal Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Protective Agents
- Antineoplastic Agents, Phytogenic
- Micronutrients
- Vitamins
- Antidotes
- Vitamin B Complex
- Docetaxel
- Carboplatin
- Paclitaxel
- Fluorouracil
- Capecitabine
- Oxaliplatin
- Leucovorin
- Albumin-Bound Paclitaxel
Other Study ID Numbers
- 2020-0122 (Other Identifier: M D Anderson Cancer Center)
- NCI-2020-05329 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Gastroesophageal Junction Adenocarcinoma
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingClinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Unresectable Gastroesophageal Junction Adenocarcinoma | Locally Advanced Gastroesophageal Junction Adenocarcinoma | Postneoadjuvant Therapy Stage III... and other conditionsUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingEsophageal Adenocarcinoma | Esophageal Squamous Cell Carcinoma | Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8 | Pathologic Stage... and other conditionsUnited States
-
Roswell Park Cancer InstitutePfizerRecruitingAdvanced Malignant Solid Neoplasm | Metastatic Colorectal Adenocarcinoma | Metastatic Gastroesophageal Junction Adenocarcinoma | Stage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Clinical Stage III... and other conditionsUnited States
-
M.D. Anderson Cancer CenterRecruitingClinical Stage III Gastric Cancer AJCC v8 | Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastric Cancer AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction... and other conditionsUnited States
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)RecruitingClinical Stage III Gastric Cancer AJCC v8 | Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastric Cancer AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction... and other conditionsUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)CompletedClinical Stage IV Gastric Cancer AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastric Adenocarcinoma | Metastatic Gastroesophageal Junction Adenocarcinoma | Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Postneoadjuvant... and other conditionsUnited States
-
NRG OncologyNational Cancer Institute (NCI)RecruitingClinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Unresectable Gastroesophageal Junction Adenocarcinoma | Postneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma... and other conditionsUnited States
-
Roswell Park Cancer InstituteUnited States Department of DefenseRecruitingClinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8 | Metastatic Gastroesophageal Junction Adenocarcinoma | Unresectable Gastroesophageal Junction Adenocarcinoma | Locally Advanced Gastroesophageal Junction... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingClinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage II Esophageal Adenocarcinoma AJCC v8 | Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8 | Clinical Stage III Esophageal Adenocarcinoma AJCC v8 | Pathologic Stage IB Esophageal Adenocarcinoma AJCC v8 | Pathologic... and other conditionsUnited States
-
Roswell Park Cancer InstituteNational Comprehensive Cancer NetworkActive, not recruitingClinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8 | Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8 | Clinical Stage III Esophageal Adenocarcinoma AJCC v8 | Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8 | Pathologic Stage IIB Esophageal Adenocarcinoma AJCC v8 | Pathologic Stage III Esophageal Adenocarcinoma AJCC v8 and other conditionsUnited States
Clinical Trials on Intensity-Modulated Radiation Therapy
-
National Cancer Institute (NCI)TerminatedLocally Recurrent Head and Neck Squamous Cell Carcinoma | Nasopharyngeal Squamous Cell Carcinoma | Sinonasal Squamous Cell CarcinomaUnited States
-
NRG OncologyNational Cancer Institute (NCI)Active, not recruitingStage II Prostate AdenocarcinomaUnited States, Canada, Hong Kong, Switzerland, India, Ireland
-
Mount Sinai Hospital, CanadaPrincess Margaret Hospital, CanadaActive, not recruitingAdult Soft Tissue SarcomaCanada, United States, Belgium
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingRecurrent Head and Neck CarcinomaUnited States
-
Institut Cancerologie de l'OuestCompletedCervical Cancer | Prostate Cancer | Anal Canal CancersFrance
-
Memorial Sloan Kettering Cancer CenterCompletedMetastatic DiseaseUnited States
-
University Health Network, TorontoOntario Cancer Research NetworkCompleted
-
Xiangya Hospital of Central South UniversityRecruitingNasopharyngeal CarcinomaChina
-
Alberta Health servicesCompleted
-
Ohio State University Comprehensive Cancer CenterNational Cancer Institute (NCI)Active, not recruitingAnatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic Stage IIIA Breast Cancer AJCC v8 | Anatomic Stage IIIB Breast Cancer AJCC v8 | Anatomic Stage IIIC Breast Cancer AJCC... and other conditionsUnited States