Low-dose Radiation Combined With Neoadjuvant Immunochemotherapy for Esophageal Squamous Cell Carcinoma
Efficacy and Safety of Low-dose Radiation Combined With Neoadjuvant Chemotherapy and Immunotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma
Sichuan University
30 participants
Jun 30, 2024
INTERVENTIONAL
Conditions
Summary
This study aims to investigate the efficacy and safety of low-dose radiation combined with neoadjuvant chemotherapy and immunotherapy in the treatment of locally advanced thoracic esophageal squamous cell carcinoma. By reducing the radiation dose from 40 Gy in 20 fractions to 4 Gy in 2 fractions, the goal is to lessen the adverse reactions caused by radiotherapy. Additionally, the study explores whether low-dose radiation therapy can promote the cross-presentation of tumor-specific antigens and increase lymphocyte infiltration into the tumor site. Study also examines whether this approach can enhance tumor-specific immune responses, thereby potentially improving the efficacy of immune checkpoint inhibitors.
Eligibility
Inclusion Criteria14
- Histologically confirmed thoracic esophageal squamous cell carcinoma with clinical staging of: cT1b-cT2 N1-2 M0 or cT3-cT4a N0-2 M0 (AJCC/UICC esophageal cancer staging, 8th edition)
- Candidates eligible for an R0 curative resection
- ECOG performance status of 0-1
- Male or female patients aged ≥18 years and ≤75 years
- Adequate major organ and bone marrow function (without transfusion or medication correction): Complete blood count: White blood cells ≥ 3.5×10\^9/L, Absolute Neutrophil Count (ANC) ≥1.5 ×10\^9/L, Platelets ≥100×10\^9/L, Hemoglobin ≥9g/dL
- Radiation oncologist assessment confirms no severe pulmonary ventilatory dysfunction and no acute cardiac failure. (Pulmonary function: FEV1/FVC≥70%, FEV1≥50% of the normal value, DLCO (lung diffusion capacity) actual versus predicted value \>80%)
- Liver function: Total bilirubin ≤1.5 times the upper limit of normal (ULN), Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) ≤2.5 times ULN, Serum albumin ≥3g/dL
- Renal function: Serum creatinine ≤1.5×ULN, or creatinine clearance ≥ 60ml/min (calculated using the Cockcroft/Gault formula): Female: CrCl = (140 - age) x weight (kg) x 0.85 / 72 x serum creatinine (mg/dL) Male: CrCl = (140 - age) x weight (kg) x 1.00 / 72 x serum creatinine (mg/dL)
- Study participants voluntarily join the study and sign a written informed consent form, and are able to comply with the protocol-specified visits and related procedures
- Expected survival \>6 months
- Patients agree to undergo surgical treatment as well as radiotherapy, chemotherapy, and immunotherapy
- Women of childbearing potential must have a negative pregnancy test within 7 days prior to the initiation of treatment; all participants, regardless of gender, are willing to use appropriate contraceptive methods during the trial and for 8 weeks after the last dose of study medication
- No esophageal perforation or active esophageal bleeding, and no tracheal or major thoracic vascular invasion
- According to the solid tumor response evaluation criteria (RECIST version 1.1), at least one measurable lesion by imaging
Exclusion Criteria11
- Patients who are unsuitable for the immunotherapy and chemotherapy specified in the protocol
- Patients with a history of treatment for ESCC, including experimental drugs, chemotherapy, radiotherapy, or therapies targeting T-cell co-stimulation checkpoint pathways such as anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies or drugs
- Patients with a history of primary tumor infiltration causing fistula
- Patients assessed as having a high risk of fistula or signs of perforation
- Patients who have required systemic corticosteroid treatment (prednisone \> 10 mg/day or equivalent dosage) or other immunosuppressive therapies within 14 days prior to the first administration. However, use of adrenocortical replacement steroids (prednisone ≤ 10 mg/day or equivalent) and minimal systemic absorption of topical, ocular, intra-articular, nasal, and inhaled corticosteroids, as well as short-term (≤ 7 days) use of corticosteroids for non-autoimmune conditions are allowed (dexamethasone can be used for paclitaxel pre-treatment)
- Patients with active autoimmune diseases or a history of autoimmune diseases that might recur. However, participants with well-controlled type 1 diabetes, hypothyroidism requiring only hormone replacement, well-controlled celiac disease, and non-systemic treated skin conditions like vitiligo, psoriasis, or alopecia, or conditions not likely to recur without an external trigger are eligible
- Patients with a history of interstitial lung disease, non-infectious pneumonia, or poorly controlled pulmonary diseases including pulmonary fibrosis or acute lung diseases
- Patients needing systemic antibacterial, antifungal, or antiviral treatment for infections such as tuberculosis. Patients who have had a severe infection including but not limited to hospitalization-required complications, bacteremia, or severe infectious pneumonia within 4 weeks before the first administration, or those who have received therapeutic oral or intravenous antibiotics within 2 weeks before the first administration
- Patients with a history of allogeneic organ transplant (excluding corneal transplant) or allogeneic hematopoietic stem cell transplant
- Patients known to be allergic to the study drug tiragolumab, or to the active ingredients or excipients in the combined chemotherapy drugs
- Patients with significant and severely symptomatic rhythm, conduction, or morphological abnormalities on a resting electrocardiogram, such as complete left bundle branch block, second-degree or higher heart block, ventricular arrhythmias, atrial fibrillation; unstable angina, congestive heart failure, or chronic heart failure with an NYHA classification of ≥ 2
Interventions
Patients will undergo two cycles of immunotherapy, each cycle lasting 21 days. Day 3 and Day 24: Tislelizumab, fixed dose of 200 mg
Patients will undergo two cycles of low-dose radiotherapy. Day 1/2 and Day 22/23: Low-dose radiotherapy (8 Gy/4f)
Patients will undergo two cycles of chemotherapy. Day 3 and Day 24: Nab-paclitaxel 260 mg/m2
Patients will undergo two cycles of chemotherapy. Day 3 and Day 24: Cisplatin 75 mg/m2.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06446726