Neoadjuvant PD-1 Blockade for Elderly Esophageal Squamous Cell Carcinoma (BLESS)

NCT06385730 | Recruiting Phase 2 DMC

• 1 other identifier: SCE2401
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will conduct a prospective phase 2 study to evaluate the efficacy and safety of neoadjuvant PD-1 blockade monotherapy with toripalimab in elderly patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC).

Conditions

Esophageal Cancer

Keywords

esophageal cancer, immunotherapy, elderly patients

Outcome Measures

Primary Outcomes (1)

• MPR rate

  A major pathological response rate (MPR) is defined as the proportion of residual living tumor cells in the post-surgery specimen within the tumor bed being less than or equal to 10%

  Through the study completion, an average of 12 months

Secondary Outcomes (7)

• pCR rate

  Through the study completion, an average of 12 months

• Adverse events and treatment-related adverse events

  Through the study completion, an average of 12 months

• R0 resection rate

  Through the study completion, an average of 12 months

• Objective Response rate

  Through the study completion, an average of 12 months

• Event-free survival (EFS)

  Through the study completion, an average of 12 months

Study Arms (2)

neoadjuvant anti-PD-1

EXPERIMENTAL

Drug: Immunotherapy Patients will receive the neoadjuvant immunotherapy with toripalimab followed by the esophagectomy.

Drug: neoadjuvant anti-PD-1

neoadjuvant anti-PD-1 with LDRT

EXPERIMENTAL

Drug: Immunotherapy Patients will receive the neoadjuvant low-dose radiotherapy plus immunotherapy with toripalimab followed by the esophagectomy.

Drug: neoadjuvant anti-PD-1 with LDRT

Interventions

neoadjuvant anti-PD-1 DRUG

PD-1 inhibitor (toripalimab) 240mg, day 1，every 3 weeks, 2 cycles. Postoperative adjuvant treatment: according to the recommendations of the guidelines and the investigators

neoadjuvant anti-PD-1

neoadjuvant anti-PD-1 with LDRT DRUG

Radiotherapy: low-dose radiotherapy (LDRT), gross target volume (GTV), DT: 1Gy (day1), 1Gy (day2), every 3 weeks, 2 cycles. PD-1 inhibitor (toripalimab) 240mg, day 3，every 3 weeks, 2 cycles. Postoperative adjuvant treatment: according to the recommendations of the guidelines and the investigators

neoadjuvant anti-PD-1 with LDRT

Eligibility Criteria

• Age: 76 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Subjects signed the informed consent and volunteered to participate in the study.
• Esophageal squamous cell carcinoma confirmed by histology or cytology.
• Thoracic esophageal squamous cell carcinoma confirmed by CT or pet-CT, which is classified as T1N1-3M0 or T2-3N0-3M0 (M1 lymph node metastasis confined to the supraclavicular lymph nodes) (AJCC 8th).
• Expect to have R0 resection
• In age \>75.
• ECOG PS: 0\~1.
• Have not received any anti-tumor treatment for esophageal cancer in the past, including radiotherapy, chemotherapy, surgery, etc.
• No contraindications to surgery.
• Has sufficient organ function including (1) Blood routine: NE≥1.5×109/L; PLT≥100×109/L; HGB≥90 g/L (2)Comprehensive Metabolic Panel: bilirubin≤ 1.5×ULN; ALT≤2.5×ULN; AST≤2.5×ULN; sCr≤1.5×ULN or CrCl≥50 mL/min（Cocheroft-Gault) (3) Coagulation function: INR≤1.5.
• Women of childbearing age must undergo a serological pregnancy test within 72 hrs before first administration. Women of childbearing age, or male subjects with childbearing age female partners, must take contraceptive measures from the first dose to five months after last administration.
• Good compliance, willing to comply with follow-up schedules.

You may not qualify if:

• Subjects have received or are receiving any of:
• anti-tumor interventions such as radiotherapy, chemotherapy, immunotherapy or other medictions.
• Received systemic corticosteroid therapy (prednisone equivalence\> 10mg/d) or other immunosuppressive agents within the first 2 weeks prior to the first administration.
• live vaccine within 4 weeks before the first administration.
• other cancers instead of ESCC
• non-recetable or metastatic ESCC
• not comply with T1N1-3M0 or T2-3N0-3M0 (AJCC 8th).
• Subjects with other malignant tumors within 5 years before the first administration, but subjects with cervical carcinoma in situ, skin basal cell carcinoma, skin squamous cell carcinoma, and localized prostate cancer received radical surgery in situ that have received radical treatment and do not need other treatment can be included).
• \. Other criteria Subjects have uncontrolled cardiovascular diseases, such as 1) heart failure ≥ NYHA class 2, 2) unstable angina 3) myocardial infarction within 1 year; 4) supraventricular or ventricular arrthymia that needs treatment Subjects with any known active autoimmune disease Pregnant or breastfeeding female Presence of allergy or hypersensitivity to investigational medications HIV positive or active hepatitis B (HbsAg positive and HBV-DNA ≥2000 IU/ml or ≥ 104 copies/mL) or active hepatitis C (HCV antibody positive) or active tuberculosis Investigators assessed there might be other factors that cause subjects to withdrawl.

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

Related Publications (3)

• Yin J, Yuan J, Li Y, Fang Y, Wang R, Jiao H, Tang H, Zhang S, Lin S, Su F, Gu J, Jiang T, Lin D, Huang Z, Du C, Wu K, Tan L, Zhou Q. Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial. Nat Med. 2023 Aug;29(8):2068-2078. doi: 10.1038/s41591-023-02469-3. Epub 2023 Jul 24.

  PMID: 37488287 BACKGROUND

• Matsuda S, Kitagawa Y, Takemura R, Okui J, Okamura A, Kawakubo H, Muto M, Kakeji Y, Takeuchi H, Watanabe M, Doki Y. Real-world Evaluation of the Efficacy of Neoadjuvant DCF Over CF in Esophageal Squamous Cell Carcinoma: Propensity Score-matched Analysis From 85 Authorized Institutes for Esophageal Cancer in Japan. Ann Surg. 2023 Jul 1;278(1):e35-e42. doi: 10.1097/SLA.0000000000005533. Epub 2022 Jul 15.

  PMID: 35837977 BACKGROUND

• Yang Y, Zhu L, Cheng Y, Liu Z, Cai X, Shao J, Zhang M, Liu J, Sun Y, Li Y, Yi J, Yu B, Jiang H, Chen H, Yang H, Tan L, Li Z. Three-arm phase II trial comparing camrelizumab plus chemotherapy versus camrelizumab plus chemoradiation versus chemoradiation as preoperative treatment for locally advanced esophageal squamous cell carcinoma (NICE-2 Study). BMC Cancer. 2022 May 6;22(1):506. doi: 10.1186/s12885-022-09573-6.

  PMID: 35524205 BACKGROUND

MeSH Terms

Conditions

Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Central Study Contacts

Zhigang Li, MD, PhD

CONTACT

86-18960619260; zhigang.li@shsmu.edu.cn

Zhichao Liu, MD, PhD

CONTACT

86-15622175948; liuzc1995@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Department of Esophageal Surgery

Study Record Dates

• First Submitted: April 23, 2024
• First Posted: April 26, 2024
• Study Start: June 17, 2024
• Primary Completion: May 1, 2025
• Study Completion (Estimated): May 1, 2027
• Last Updated: July 1, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)