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

Neoadjuvant Nivolumab Plus Paclitaxel/ Cisplatin- Chemo- Radiotherapy (Neo-NTP-CRT) Followed by Esophagectomy for Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)

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

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Anticipated): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ta-Chen Huang, MD; Phone Number: 71669 +886223123456; Email: e360215@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Ta-Chen Huang, MD; Phone Number: 71669 +886223123456; Email: e360215@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neo-CRT; 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).	Drug: Nivolumab; adding nivolumab to conventional neoadjuvant CRT; Other Names: cisplatin; radiation; paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in treatment related death	no increase of treatment-related death within 30 days after esophagectomy	30 days
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.).	5 months

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Chih-Hung Hsu, MD PhD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2021
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: October 24, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): November 23, 2021

Study Record Updates

• Last Update Posted (Actual): November 23, 2021
• Last Update Submitted That Met QC Criteria: November 22, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Paclitaxel; Cisplatin; Nivolumab
• Other Study ID Numbers: 202005115MIPB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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