Combining low-dose radiation with immunochemotherapy for esophageal cancer treatment

Efficacy and Safety of Low-dose Radiation Combined With Neoadjuvant Chemotherapy and Immunotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma

This study is testing whether using low-dose radiation along with chemotherapy and immunotherapy can help improve treatment outcomes for patients with advanced esophageal cancer before surgery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sichuan University (other)
• Drugs / interventions: tiragolumab, chemotherapy, immunotherapy, Radiation, prednisone, tislelizumab
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT06446726 on ClinicalTrials.gov

What this trial studies

This study investigates the efficacy and safety of low-dose radiation combined with neoadjuvant chemotherapy and immunotherapy for patients with locally advanced thoracic esophageal squamous cell carcinoma. The approach reduces the radiation dose significantly to minimize adverse reactions while exploring its potential to enhance immune responses against tumors. The study aims to determine if this combination can improve clinical outcomes for patients who are candidates for surgery. It also assesses the impact of low-dose radiation on tumor-specific immune responses and lymphocyte infiltration.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with histologically confirmed locally advanced thoracic esophageal squamous cell carcinoma eligible for curative surgery.

Not a fit: Patients with severe pulmonary dysfunction or acute cardiac failure may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved treatment outcomes and survival rates for patients with esophageal squamous cell carcinoma.

How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and chemotherapy, indicating potential for success in this novel approach.

Eligibility criteria

Inclusion Criteria:

1. 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)
2. Candidates eligible for an R0 curative resection
3. ECOG performance status of 0-1
4. Male or female patients aged ≥18 years and ≤75 years
5. 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
6. 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%)
7. 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
8. 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)
9. 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
10. Expected survival \>6 months
11. Patients agree to undergo surgical treatment as well as radiotherapy, chemotherapy, and immunotherapy
12. 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
13. No esophageal perforation or active esophageal bleeding, and no tracheal or major thoracic vascular invasion
14. According to the solid tumor response evaluation criteria (RECIST version 1.1), at least one measurable lesion by imaging

Exclusion Criteria:

1. Patients who are unsuitable for the immunotherapy and chemotherapy specified in the protocol
2. 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
3. Patients with a history of primary tumor infiltration causing fistula
4. Patients assessed as having a high risk of fistula or signs of perforation
5. 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)
6. 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
7. Patients with a history of interstitial lung disease, non-infectious pneumonia, or poorly controlled pulmonary diseases including pulmonary fibrosis or acute lung diseases
8. 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
9. Patients with a history of allogeneic organ transplant (excluding corneal transplant) or allogeneic hematopoietic stem cell transplant
10. Patients known to be allergic to the study drug tiragolumab, or to the active ingredients or excipients in the combined chemotherapy drugs
11. 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

Where this trial is running

Chengdu, Sichuan

• Sichuan University West China Hospital — Chengdu, Sichuan, China (RECRUITING)

Study contacts

• Principal investigator: Jianxin Xue, professor — West China Hospital
• Study coordinator: Yong Yuan, Professor

Conditions: Esophageal Squamous Cell Carcinoma, Esophageal squamous cell carcinoma, low-dose radiation, neoadjuvant immunochemotherapy