A Study of Toripalimab Combined With Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma.

NCT04084158 | Suspended Phase 2

• 1 other identifier: IESO001
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to explore the efficacy and safety of Toripalimab injection (JS001) given before and after concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

Esophageal Squamous Cell Carcinoma; PD-1 antibody

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression-Free Survival

  2 years

Secondary Outcomes (4)

• Objective Response Rate

  analysis is completed 4 weeks after concurrent chemoradiation

• OS

  3 years

• DoR

  2 years

• TTDM

  3 years

Study Arms (2)

Toripalimab+chemoradiation

EXPERIMENTAL

Induction immunotherapy: Toripalimab injection (JS001) 3mg/kg IV q 14 days x 2 cycles. Concurrent Chemoradiotherapy: Starting within 4 weeks after the first cycle induction immunotherapy. carboplatin AUC = 2 + albumin-bound paclitaxel 60 mg/m2 or paclitaxel liposome 45 mg/m2 or paclitaxel 45 mg/m2 IV weekly x 6 weeks concurrent with radiation to a total dose of 50.4 Gy given in 1.8 Gy fractions daily x 28 fractions. Progression of disease (PD): The progress of the disease will be assessed within 4 weeks after concurrent chemoradiotherapy. Patients without disease progression continue to receive consolidation and adjuvant therapy. Consolidation chemotherapy: carboplatin AUC = 6 + albumin-bound paclitaxel 260 mg/m2 or paclitaxel liposome 135 mg/m2 or paclitaxel 135 mg/m2 IV q 21 days x 6 cycles. Adjuvant immunotherapy:Toripalimab injection (JS001) 3mg/kg IV q 14 days up to 1 year.

Drug: Toripalimab injection (JS001); Drug: Paclitaxel, Albumin-Bound; Radiation: Radiotherapy; Drug: Platinum-Based Drug

chemoradiation

ACTIVE COMPARATOR

Concurrent Chemoradiotherapy: carboplatin AUC = 2 + albumin-bound paclitaxel 60 mg/m2 or Liposome paclitaxel 45 mg/m2 or paclitaxel 45 mg/m2 IV weekly x 6 weeks concurrent with radiation to a total dose of 50.4 Gy given in 1.8 Gy fractions daily x 28 fractions. Progression of disease (PD): The progress of the disease will be assessed within 4 weeks after concurrent chemoradiotherapy. Patients without disease progression continue to receive consolidation therapy. Consolidation chemotherapy: carboplatin AUC = 6 + albumin-bound paclitaxel 260 mg/m2 or paclitaxel liposome 135 mg/m2 or paclitaxel 135 mg/m2 IV q 21 days x 6 cycles.

Drug: Paclitaxel, Albumin-Bound; Radiation: Radiotherapy; Drug: Platinum-Based Drug

Interventions

Toripalimab injection (JS001) DRUG

Toripalimab injection (JS001) is a humanized IgG4 monoclonal antibody against the programmed death-1 (PD-1) receptor, blocks the interaction of PD-1 with its ligands and promotes T cell activation in preclinical studies.

Toripalimab+chemoradiation

Paclitaxel, Albumin-Bound DRUG

Paclitaxel

Toripalimab+chemoradiation; chemoradiation

Radiotherapy RADIATION

PTV 50.4Gy/28 fractions, PGTV 61.6Gy/28 fractions, once a day, 5 days a week.

Toripalimab+chemoradiation; chemoradiation

Platinum-Based Drug DRUG

carboplatin

Toripalimab+chemoradiation; chemoradiation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≤age≤75.
• Histologically or cytologically confirmed esophageal squamous carcinoma.
• Patients must have unresectable disease as assessed by thoracic surgeons or refuse surgical treatment.
• The investigator confirmed at least one measurable lesion according to RECIST 1.1.
• Stage II-IVA (AJCC 8th)
• No adjacent organs infringed confirmed by endoscopic ultrasonography (T1-3).
• ECOG PS 0-1.
• FEV1\>0.8L
• Life expectancy is not less than 12 weeks.
• No prior chemotherapy, radiotherapy, biotherapy, immunotherapy or other anti-tumor treatment for esophageal cancer.
• Adequate organ function defined at baseline as: 1) ANC ≥1.5×109 /L，PLt ≥100×109 /L，Hb ≥90 g/L; 2) TBIL ≤1.5×ULN, ALT ≤2.5ULN, AST ≤2.5ULN, BUN and Cr ≤1×ULN or Ccr ≥50ml/min (Cockcroft-Gault formula); 3) INR ≤1.5×ULN or PT ≤1.5×ULN (If the patient is receiving anticoagulant therapy, PT should be within the intended use range of the anticoagulant drug); 4) Myocardial zymogram is within normal range.
• Women of childbearing age must have taken reliable contraceptive measures or have a pregnancy test (serum or urine) within 7 days prior to enrollment and the results are negative. Besides, subjects should agree to use effective methods of contraception during the trial and within 2 months of the last dose of anti-PD-1 antibody. For male subjects whose spouse are of childbearing age, effective contraceptive methods should be used during the trial and within 2 months after the last dose of anti-PD-1 antibodies;
• Subject volunteers to join the study, Signs informed consent, has good compliance and can cooperate with follow-up.

You may not qualify if:

• Those with prior or concurrent uncured malignant tumor. cured skin basal cell carcinoma, cervical cancer and superficial bladder cancer were excluded.
• Esophageal cancer patients with primary multifocal lesions.
• Those with the pathology of small cell esophageal carcinoma, esophageal adenocarcinoma or mixed carcinoma.
• Primary esophageal squamous carcinoma with active hemorrhage of the primary lesion within 2 months.
• Those with primary esophageal lesion that was closely related to tracheal bronchus and great vessels, and were evaluated with a great risk of perforation and massive bleeding by the researchers.
• Patients with any active autoimmune disease or autoimmune disease history (such as interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, and hypothyroidism (those with normal thyroid function after hormone replacement therapy could be enrolled); those with leucoderma or childhood asthma that was completely relieved and required no intervention during adulthood could be enrolled, while asthma patients requiring bronchodilators and medical intervention should not be enrolled.
• Patients with uncontrolled cardiovascular disease: grade II and above myocardial ischemia or myocardial infarction, and poorly-controlled arrhythmia (including the QTc interval of ≥470 ms); those with grade III-IV cardiac insufficiency according to the NYHA criteria, or those whose echocardiography revealed left ventricular ejection fraction (LVEF) of \<50%; and those having myocardial infarction within 1 year.
• Those with active infection or fever of \>38.5 ℃ with unknown cause during the screening period and before the first administration (patients with tumor-induced fever judged by the researchers could be enrolled).
• Those with interstitial lung disease or active non-infectious pneumonia history or evidence.
• Those with congenital or acquired immunodeficiency (such as those with HIV infection), active hepatitis B (HBV-DNA≥104 copies/ml) or hepatitis C (positive hepatitis C antibody, and the HCR-RNA was higher than the lower limit of detection of the analysis method).
• Those who had previously received other PD-1 antibody treatment or PD-1/PD-L1 targeted immune therapy.
• Those who were known to be allergic to paclitaxel, carboplatin, macromolecular protein preparation, or any anti-PD-1 antibody component.
• Subjects who required to use corticosteroids (prednison dose of \> 10 mg/day) or other immunosuppressors for systemic treatment within the first 7 days of research. In the absence of active autoimmune disease, glucocorticoids at physiological dose (≤ 10 mg/day prednison or equivalent drug), inhalation or local application of steroid and adrenocortical hormone replacement treatment with prednison at the dose of \> 10 mg/day.
• Those receiving anti-tumor monoclonal antibody (mAb) and targeted small molecule treatment within 4 weeks before the initial use of the research drug, or those with unrecovered adverse events induced by the previous treatment (namely, grade ≤ 1 or reaching the baseline level). Apart from subjects with ≤ grade 2 nervous lesion or ≤ grade 2 alopecia, any subject that had received major surgery should sufficiently recover from the toxic reaction and/or complication resulted from the surgical intervention before the initiation of treatment.
• Those who were within 4 weeks before the initial use of the research drug (subjects that had entered the follow-up period were calculated at the final use of experimental drug or instrument) or those who were participating other clinical research.

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

toripalimab; Albumin-Bound Paclitaxel; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Therapeutics

Study Officials

• Chen Ming, MD

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

• Yujin Xu, MD

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2019
• First Posted: September 10, 2019
• Study Start: September 7, 2019
• Primary Completion: December 30, 2021
• Study Completion: December 30, 2021
• Last Updated: February 23, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)