Clinical trial NCT06061146: Tislelizumab Plus Concurrent Chemoradiation in Older With ESCC
Official title: Tislelizumab Combined With Concurrent Chemoradiation Versus Concurrent Chemoradiation for Older Patients With Inoperable Locally Advanced Esophageal Squamous Cell Carcinoma: a Randomized, Parallel-controlled, Multicenter Phase II Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Esophageal Cancer
Keywords: Old Age
Esophageal Cancer
Tislelizumab
Concurrent Chemoradiotherapy
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
Collaborators: name: Sichuan Cancer Hospital and Research Institute
name: Shanxi Province Cancer Hospital
name: Henan Cancer Hospital
name: Hunan Cancer Hospital
name: The First Affiliated Hospital with Nanjing Medical University
First posted: 2023-09-29
Enrollment: 136
Sex: ALL
Minimum age (years): 70
Maximum age (years): 90
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was conducted in elderly (≥70 years old) patients with locally advanced esophageal squamous cell carcinoma. Aim to find the difference in efficacy and safety between tirilizumab combined with concurrent chemoradiation and standard concurrent chemoradiation.

Concurrent chemoradiation is the standard treatment for elderly esophageal cancer. Tirelizumab is the first-line and second-line standard treatment for advanced esophageal squamous carcinoma. However, the effect of tirilizumab combined with concurrent chemoradiation for elder with locally advanced esophageal squamous cell carcinoma is unkown.

In the study, the investigators plan to enroll 136 elderly subjects with locally advanced esophageal cancer from five hospitals in China. The enrolled patients will be randomly divided into two groups: tirilizumab combined with concurrent chemoradiation group (Tislelizumab + radiotherapy + tigio) and concurrent chemoradiation group (radiotherapy + tigio). The treatment efficiency and safety will be evaluated.


Eligibility criteria: Inclusion Criteria:

1. Volunteered to participate, cooperated with follow-up visits;
2. Aged ≥ 70 years, both male and female;
3. Histologically confirmed cT1N2-3M0 or cT2-4bN0-3M0 or cT1-4bN0-3M1(supraclavicular lymph node metastasis) locally advanced ESCC (8th AJCC );
4. Clinically staged as II-IVb inoperable locally advanced ESCC(including non-resectable, or with contraindications to or refusal of surgery);
5. ECOG performance status 0 or 1;
6. Presence of measurable and/or non-measurable lesions as defined by RECIST 1.1;
7. Haven't received any previous systemic anti-tumor therapy (including but not limited to systemic chemotherapy, radiotherapy, molecularly targeted drug therapy, immunotherapy, biologic therapy, topical therapy and other investigational therapeutic agents);
8. Provide fresh or archived tumour tissue samples within 6 months (fresh samples preferred) for biomarker analysis (e.g.PD-L1). Sample types are formalin-fixed, paraffin-embedded \[FFPE\] tumour tissue blocks or at least 5 unstained, 3-5 μm thick FFPE tumour tissue sections;
9. Expected survival ≥ 3 months;
10. Adequate hematologic function, defined as ANC ≥1500/μl, platelet count ≥100,000/μl and hemoglobin count ≥9.0 g/dl or ≥5.6 mmol/l;
11. Adequate renal function, defined as creatinine ≤1.5× ULN or measured or calculated creatinine clearance ≥60 mL/min for those with creatinine levels \>1.5× ULN (Calculated from the Cockcroft-Gault formula);
12. Adequate hepatic function, defined as total bilirubin ≤1.5× ULN and ALT/AST/AKP levels ≤2.5× ULN and albumin ≥2.8 g/dl;
13. Adequate coagulation function, defined as INR ≤1.5× ULN and APTT≤1.5× ULN unless the patient is receiving anticoagulant therapy as long as INR is within the therapeutic range;
14. Documented informed consent.

Exclusion Criteria:

1. Surgery for esophageal cancer;
2. Esophageal fistulae due to infiltration of the primary tumour;
3. Risk of gastrointestinal bleeding, oesophageal fistula or oesophageal perforation
4. Poor nutritional status, weight loss of ≥10% in the previous 2 months, with no significant improvement after nutritional intervention;
5. Major surgery or severe trauma within 4 weeks prior to first use of study drug;
6. Uncontrollable pleural effusion, pericardial effusion, or ascites that requires repeated drainage;
7. Received or receiving any of the following treatments in the past:

   1. Anti-PD-1 or anti-PD-L1 antibody therapy, chemotherapy, radiotherapy or targeted therapy;
   2. Participation in a study of an investigational agent or device within 4 weeks before the first dose of study treatment;
   3. Systemic treatment with corticosteroids (\>10 mg prednisone equivalent dose per day) or other immunosuppressive agents is required for 2 weeks before the first dose of study treatment(except for the use of corticosteroids for local inflammation of the oesophagus and for the prevention of allergy and nausea and vomiting). Other special circumstances need to be communicated to the sponsor.Inhaled or topical steroids and adrenocorticotropic hormone replacement at doses \>10mg/day prednisone efficacy dose are permitted if the patient does not have active autoimmune disease;
   4. Received an anti-tumour vaccine or received a live vaccine within 4 weeks before the first dose of study treatment;
8. Any active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonitis, uveitis, enteritis, hepatitis, pituitary gland inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism);Except for patients with vitiligo or those who had asthma or allergies in childhood but did not need any intervention as adults; patients with autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone and type I diabetes mellitus treated with stable doses of insulin may be included;
9. Diagnosis of immunodeficiency, including positive HIV test,other acquired/congenital immunodeficiency diseases, organ transplantation and allogeneic bone marrow transplantation;
10. Diagnosis of uncontrolled cardiac clinical symptoms or disease such as a.NYHA II or above heart failure b.unstable angina c.myocardial infarction within 1 year d.clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention;
11. Severe infections (CTC AE \> Grade 2), such as severe pneumonia requiring hospitalisation, bacteraemia, infectious co-morbidities, etc., within 4 weeks before the first use of study treatment; Baseline chest imaging suggestive of active lung inflammation, signs and symptoms of infection requiring oral or intravenous antibiotic treatment within 2 weeks before the first use of study treatment, except for prophylactic antibiotic use;
12. History of interstitial lung disease or non-infectious pneumonia, or pulmonary insufficiency ≥ grade 3 as confirmed by pulmonary function tests;
13. Active tuberculosis infection detected by history or CT examination, or history of active tuberculosis infection within 1 year before enrollment or more than 1 year previously without regular treatment;
14. Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive and HCV-RNA above the lower limit of detection);
15. Presence of abnormal sodium, potassium, and calcium laboratory test values greater than Grade 1 within 2 weeks prior to randomisation that do not improve with treatment;
16. Known hypersensitivity to large protein preparations, or to any of the components of tirilizumab, or anaphylaxis, hypersensitivity, or contraindication to paclitaxel or cisplatin or to any of the components used within their preparations;

Primary outcomes:
measure: PFS
timeFrame: up to 2 years
Secondary outcomes:
measure: OS
timeFrame: up to 2 years
measure: ORR
timeFrame: up to 2 years
measure: DoR
timeFrame: up to 2 years
measure: AE
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
Study officials:
affiliation: Tian jin cancer hospital
name: Wencheng Zhang, M.D
role: PRINCIPAL_INVESTIGATOR
References: