Immunotherapy in Combination With Chemoradiotherapy in Unresectable Locally Advanced Esophageal Cancer

Phase 1

Recruiting

• Conditions: Unresectable Locally Advanced Esophageal Cancer; Esophageal Squamous Cell Carcinoma
• Interventions: Drug: PD-1inhibitor; Drug: nab-paclitaxel + cisplatin; Radiation: Radiotherapy

• Registration Number: NCT06173986
• Lead Sponsor: Shanghai Chest Hospital

Brief Summary

SCR-ESCC-02 is a multicenter, phase I/II clinical study to investigate the safety and efficacy of induction immunochemotherapy followed by concurrent chemoradiotherapy with anti-PD-1 therapy in patients diagnosed with locally advanced, unresectable esophageal cancer.

Detailed Description

Immunotherapy has shown promising results in advanced esophageal cancer, but its optimal integration into the management of unresectable locally advanced disease remains uncertain. The significant tumor regression and reduced tumor residual achieved through immunochemotherapy offer an opportunity to enhance the effectiveness of subsequent radiotherapy. This phase I/II clinical study aims to investigate the efficacy and safety of induction immunochemotherapy followed by concurrent chemoradiotherapy with anti-PD-1 for patients with unresectable locally advanced esophageal cancer. The study's co-primary endpoints are progression-free survival (PFS) and treatment completion rate.

Study Timeline

• Study Start: 2023-01-10
• Status Verified: 2023-12
• Study First Submitted: 2023-12-08
• Study First Submitted QC: 2023-12-15
• Last Update Submitted: 2023-12-15
• Study First Posted: 2023-12-18
• Last Update Posted: 2023-12-18
• Primary Completion: 2025-12-30
• Study Completion: 2027-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Age between 18 and 75 years.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
3. Clinical stage meeting the criteria of T1N+M0 or T2-4aN0-3M0 based on the 8th UICC-TNM classification.
4. Ineligibility for surgical resections due to patients' unwillingness for surgery, technically unresectable disease, or being medically unfit for surgery.
5. No prior anti-tumor treatment, including surgery, radiotherapy, chemotherapy, immunotherapy, or targeted therapy.
6. Adequate hematological, pulmonary, cardiac, hepatic, renal, and thyroid function.
7. Willingness to use contraception with an adequate method throughout the study.
8. Documented informed consent.

Exclusion Criteria

1. History of malignant disease within the 5 years preceding enrollment or presence of other malignant tumors or non-squamous cell carcinoma components.

2. High risk of gastrointestinal bleeding, esophageal fistula, or esophageal perforation as determined by the investigators.

3. Weight loss exceeding 20% within the 90 days prior to the first day of drug administration.

4. Presence of long-standing unhealed wounds or fractures or undergoing major surgical resections within 60 days preceding the first day of drug administration.

5. Presence of any severe or uncontrolled coexisting diseases, including but not limited to:

   • Uncontrolled hypertension
   • History of interstitial lung disease or non-infectious pneumonia
   • Active hepatitis B or C, syphilis, or other active and uncontrolled infections
   • Cardiac insufficiency (NYHA≥2)
   • Renal dysfunction requiring dialysis
   • Active autoimmune disease
   • History of acquired or congenital immunodeficiency diseases

6. Occurrence of serious arterial/venous thrombotic events within 6 months prior to the first day of drug administration.

7. History of psychotropic substance abuse or inability to quit, or patients with psychotic disorders.

8. Allergy to study drugs.

9. Patients deemed unsuitable for participation due to severe comorbidities or other reasons determined by the investigators.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IC+ICRT group	PD-1inhibitor	2 cycles of PD-1 inhibitor + nab-paclitaxel + cisplatin followed by concurrent PD-1 inhibitor + radiotherapy (45-50Gy/25fx) + nab-paclitaxel + cisplatin
IC+ICRT group	nab-paclitaxel + cisplatin	2 cycles of PD-1 inhibitor + nab-paclitaxel + cisplatin followed by concurrent PD-1 inhibitor + radiotherapy (45-50Gy/25fx) + nab-paclitaxel + cisplatin
IC+ICRT group	Radiotherapy	2 cycles of PD-1 inhibitor + nab-paclitaxel + cisplatin followed by concurrent PD-1 inhibitor + radiotherapy (45-50Gy/25fx) + nab-paclitaxel + cisplatin

Primary Outcome Measures

Name	Time	Method
Progression-free survival	Assessed up to 60 months	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first
Treatment completion rate	1 year	The Treatment Completion Rate is defined as the percentage of patients who successfully completed concurrent immuno-chemoradiotherapy.

Secondary Outcome Measures

Name	Time	Method
Objective response rate	1 year	Objective response rate (ORR), defined as the proportion of patients with a complete response or partial response after Immuno-Chemoradiotherapy according to Response Evaluation Criteria in Solid Tumors (RECIST)
Overall survival	Assessed up to 60 months	From date of randomization until the date of death from any cause
Incidence of Adverse events (AE) or severe adverse events (SAE)	1 year	Adverse events (AE) or severe adverse events (SAE) occurring within 3 months post-radiotherapy, and the incidence of treatment discontinuation due to AE/SAE

Trial Locations

Locations (1)

Shanghai Chest Hospital; 🇨🇳 Shanghai, China