search
Back to results

Neo-NTP-CRT for Locally Advanced ESCC (Neo-NTP-CRT)

Primary Purpose

Locally Advanced Esophageal Squamous Cell Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
Taiwan
Study Type
Interventional
Intervention
Nivolumab
Sponsored by
National Taiwan University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Esophageal Squamous Cell Carcinoma

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Pathologically proven squamous cell carcinoma of the intrathoracic esophagus.
  2. Locally advanced disease, which is defined by the TNM system of the American Joint Committee on Cancer (AJCC) Cancer Staging System (8th edition), fulfilling one of the following criteria as determined by endoscopic ultrasound, computed tomography, bronchoscopy and positron emission tomography:

    1. cT3/4a, N0, M0;
    2. cT1-3, N1-3, M0.
  3. Tumor length longitudinal ≤ 8cm and radial ≤ 5cm.
  4. The tumor must not extend more than 2cm into the stomach.
  5. No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula.
  6. Age ≥ 20 and ≤ 75 years old.
  7. Performance status ECOG 0~1.
  8. Adequate bone marrow reserves, defined as:

    1. white blood cells (WBC) ≥ 4,000/µl or neutrophil count (ANC) ≥ 2,000/µl;
    2. platelets ≥ 100,000/µl.
  9. Adequate liver function reserves, defined as:

    1. hepatic transaminases ≤ 2.5 x upper limit of normal (ULN);
    2. serum total bilirubin ≤ 2.0 x upper limit of normal (ULN).
  10. Adequate renal function: Creatinine ≤1.5 x upper normal limit or estimated creatinine clearance ≥ 50 ml/min (estimated by Cockcroft-Gault formulation)
  11. Written informed consent.
  12. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  13. Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section - Contraception, for the course of the study through 120 days after the last dose of study medication.

    Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

  14. Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section - Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria:

  1. Adenocarcinoma.
  2. Previous thoracic irradiation.
  3. Previous systemic chemotherapy
  4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  5. Synchronously diagnosed squamous cell carcinoma of aerodigestive way, other than esophageal cancer.
  6. Prior malignancy, except for the following:

    1. adequately treated basal cell or squamous cell skin cancer;
    2. in-situ cervical cancer;
    3. a "cured" malignancy more than 5 years prior to enrollment.
  7. Significant co-morbid disease, which prohibits the conduction of chemotherapy, concurrent chemo- radiotherapy, or radical surgery, such as active systemic infection, symptomatic cardiac or pulmonary disease, or psychiatric disorders.
  8. Documented myocardial infarction within the 6 months preceding registration (pretreatment ECG evidence of infarct only will not exclude patients). Patients with a history of significant ventricular arrhythmia requiring medication. Patients with a history of 2nd or 3rd degree heart block.
  9. Pre-existing motor or sensory neurotoxicity greater than grade 1.
  10. Patients with prior allergic reactions to drug containing Cremophor, such as teniposide or cyclosporine.
  11. Weight loss > 15%.
  12. Dementia or altered mental status that would prohibit the understanding and completion of informed consent.
  13. Estimated life expectancy less than 3 months.
  14. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  15. Has a known history of active TB (Bacillus Tuberculosis)
  16. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  17. Has known history of, or any evidence of active, non-infectious pneumonitis, interstitial lung disease or pulmonary fibrosis.
  18. Concurrent diverticulitis or symptomatic gastrointestinal ulcerative disease.
  19. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  20. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  21. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., anti-HCV reactive and HCV RNA [qualitative] are detected).
  22. Patients with a negative HBs antigen test but a positive test result for either HBs antibody or HBc antibody with a detectable level of HBV-DNA.
  23. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  24. Has received organ transplantation.

Sites / Locations

  • National Taiwan University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neo-CRT

Arm Description

Nivolumab 240 mg, 30-min IVF, Q2W on days -14, 1, 15, and 29; Paclitaxel 50 mg/m2, 1h-IVF, on days 1, 8, 15, 22, and 29; Cisplatin 30 mg/m2,1h-IVF,on days 1, 8,15, 22, and 29; RT: 1.8 Gy/fraction, 5 days a week, for 25 fractions (total dose= 45 Gy).

Outcomes

Primary Outcome Measures

change in treatment related death
no increase of treatment-related death within 30 days after esophagectomy
rate of completion of protocol treatment
successful completion of preoperative therapy and processing to surgery without any extended treatment-related delay, which is defined as > 19 weeks after the first dose of nivolumab (d-14) in neo-NTP-CRT (19 weeks include 15 weeks of protocol treatment plus 4 weeks of flexibility.).

Secondary Outcome Measures

Full Information

First Posted
October 24, 2021
Last Updated
November 22, 2021
Sponsor
National Taiwan University Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT05130684
Brief Title
Neo-NTP-CRT for Locally Advanced ESCC
Acronym
Neo-NTP-CRT
Official Title
Neoadjuvant Nivolumab Plus Paclitaxel/ Cisplatin- Chemo- Radiotherapy (Neo-NTP-CRT) Followed by Esophagectomy for Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Recruiting
Study Start Date
February 22, 2021 (Actual)
Primary Completion Date
March 1, 2023 (Anticipated)
Study Completion Date
March 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Taiwan University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The investigators hypothesize that nivolumab combined with neoadjuvant chemoradiotherapy (CRT) is safe and effective in patients with locally advanced esophageal squamous cell carcinoma (LAESCC).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Esophageal Squamous Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
43 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Neo-CRT
Arm Type
Experimental
Arm Description
Nivolumab 240 mg, 30-min IVF, Q2W on days -14, 1, 15, and 29; Paclitaxel 50 mg/m2, 1h-IVF, on days 1, 8, 15, 22, and 29; Cisplatin 30 mg/m2,1h-IVF,on days 1, 8,15, 22, and 29; RT: 1.8 Gy/fraction, 5 days a week, for 25 fractions (total dose= 45 Gy).
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
paclitaxel, cisplatin, radiation
Intervention Description
adding nivolumab to conventional neoadjuvant CRT
Primary Outcome Measure Information:
Title
change in treatment related death
Description
no increase of treatment-related death within 30 days after esophagectomy
Time Frame
30 days
Title
rate of completion of protocol treatment
Description
successful completion of preoperative therapy and processing to surgery without any extended treatment-related delay, which is defined as > 19 weeks after the first dose of nivolumab (d-14) in neo-NTP-CRT (19 weeks include 15 weeks of protocol treatment plus 4 weeks of flexibility.).
Time Frame
5 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathologically proven squamous cell carcinoma of the intrathoracic esophagus. Locally advanced disease, which is defined by the TNM system of the American Joint Committee on Cancer (AJCC) Cancer Staging System (8th edition), fulfilling one of the following criteria as determined by endoscopic ultrasound, computed tomography, bronchoscopy and positron emission tomography: cT3/4a, N0, M0; cT1-3, N1-3, M0. Tumor length longitudinal ≤ 8cm and radial ≤ 5cm. The tumor must not extend more than 2cm into the stomach. No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula. Age ≥ 20 and ≤ 75 years old. Performance status ECOG 0~1. Adequate bone marrow reserves, defined as: white blood cells (WBC) ≥ 4,000/µl or neutrophil count (ANC) ≥ 2,000/µl; platelets ≥ 100,000/µl. Adequate liver function reserves, defined as: hepatic transaminases ≤ 2.5 x upper limit of normal (ULN); serum total bilirubin ≤ 2.0 x upper limit of normal (ULN). Adequate renal function: Creatinine ≤1.5 x upper normal limit or estimated creatinine clearance ≥ 50 ml/min (estimated by Cockcroft-Gault formulation) Written informed consent. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section - Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section - Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Exclusion Criteria: Adenocarcinoma. Previous thoracic irradiation. Previous systemic chemotherapy Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. Synchronously diagnosed squamous cell carcinoma of aerodigestive way, other than esophageal cancer. Prior malignancy, except for the following: adequately treated basal cell or squamous cell skin cancer; in-situ cervical cancer; a "cured" malignancy more than 5 years prior to enrollment. Significant co-morbid disease, which prohibits the conduction of chemotherapy, concurrent chemo- radiotherapy, or radical surgery, such as active systemic infection, symptomatic cardiac or pulmonary disease, or psychiatric disorders. Documented myocardial infarction within the 6 months preceding registration (pretreatment ECG evidence of infarct only will not exclude patients). Patients with a history of significant ventricular arrhythmia requiring medication. Patients with a history of 2nd or 3rd degree heart block. Pre-existing motor or sensory neurotoxicity greater than grade 1. Patients with prior allergic reactions to drug containing Cremophor, such as teniposide or cyclosporine. Weight loss > 15%. Dementia or altered mental status that would prohibit the understanding and completion of informed consent. Estimated life expectancy less than 3 months. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Has a known history of active TB (Bacillus Tuberculosis) Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Has known history of, or any evidence of active, non-infectious pneumonitis, interstitial lung disease or pulmonary fibrosis. Concurrent diverticulitis or symptomatic gastrointestinal ulcerative disease. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., anti-HCV reactive and HCV RNA [qualitative] are detected). Patients with a negative HBs antigen test but a positive test result for either HBs antibody or HBc antibody with a detectable level of HBV-DNA. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. Has received organ transplantation.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ta-Chen Huang, MD
Phone
+886223123456
Ext
71669
Email
e360215@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chih-Hung Hsu, MD PhD
Organizational Affiliation
National Taiwan University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ta-Chen Huang, MD
Phone
+886223123456
Ext
71669
Email
e360215@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Neo-NTP-CRT for Locally Advanced ESCC

We'll reach out to this number within 24 hrs