Immunotherapy With CCRT Followed by Surgery for Locally Advanced ESCC Patients

NCT05743504 | Unknown Phase 1 DMC

• 2 other identifiers: 202111099MIPCML43431
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The prognosis of ESCC is poor with a five-year overall survival rate of 10 to 30 %. Randomized clinical trials have demonstrated that TMT, consisted of neoadjuvant concurrent CCRT and radical esophagectomy, improves the overall survival for patients with resectable locally advanced disease. As a consequence, it is mandatory to develop new pharmacotherapeutic regimen for TMT. In our previous prospective studies, we found higher levels of serum immune-related biomarkers, VEGF-A, TGF-β1, and soluble PD-L1, before neoadjuvant CCRT were independent associated with inferior overall survival and disease-free survival for locally advanced ESCC treated with neoadjuvant CCRT plus radical esophagectomy. In the present clinical trial, we plan to investigate whether incorporation of tiragolumab (Anti-TIGIT) and atezolizumab (Anti-PD-L1) into standard TMT will be safe while improve the pathological complete response rate. By the present research, we expect to develop a new TMT regimen for this poor prognostic disease.

Conditions

Locally Advanced Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate

  Pathological complete response rate after radical esophagectomy with or without adding tiragolumab/atezolizumab to neoadjuvant paclitaxel-platinum concurrent chemoradiation

  Through study treatment, around 4 to 5 months

Secondary Outcomes (7)

• Side effect evaluation

  30 days

• Side effect evaluation

  30 days

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Within 30 days

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  over 30 days

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Less than 90 days from last tiragolumab/atezolizumab administration

Study Arms (1)

Immunotherapy with CCRT before surgery

EXPERIMENTAL

Tiragolumab and Atezolizumab with CCRT before surgery

Drug: Tiragolumab

Interventions

Tiragolumab DRUG

Neoadjuvant Tiragolumab, Atezolizumab, Paclitaxel, Cisplatin and Radiotherapy Followed by Surgery

Also known as: Atezolizumab, Paclitaxel, Cisplatin, Radiotherapy, Surgery

Immunotherapy with CCRT before surgery

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proved squamous cell carcinoma of esophagus
• Locally advanced disease, which are defined by TNM system of American Joint Committee on Cancer (AJCC) Cancer Staging System (8th edition) in 2017, fulfilling one of the following criteria:
• T1-2N2-3M0
• T3N1-3M0
• Tumor judged to be operable and resectable with curative intent on the screening assessment
• Age ≥ 20 years
• Medical fit for curative surgery
• ECOG Performance Status 0 or 1
• Adequate bone marrow reserves within 2 weeks prior to registration, defined as:
• absolute neutrophil count (ANC) ≥ 1.5×109/L (1,500/μl)
• platelets ≥ 100×109/L (100,000/µl)
• hemoglobin ≥ 9.0 g/dl (may have been transfused)
• Adequate liver function reserves within 2 weeks prior to registration, defined as:
• hepatic transaminases (AST and ALT) ≤ 2.5 × upper limit of normal (ULN)
• serum total bilirubin ≤ 1.5 × upper limit of normal (ULN)

You may not qualify if:

• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-¬CTLA-4, anti-PD-1, anti-PD-L1 and anti-¬TIGIT therapeutic antibodies
• Prior radiotherapy to head and neck, chest, or abdomen
• Prior chemotherapy
• Histology consistent with adenocarcinoma, small cell carcinoma or mixed carcinoma of esophagus or gastroesophageal junction.
• Synchronously or metachronously diagnosed squamous cell carcinoma of aerodigestive way, other than esophageal cancer
• History of malignancy other than esophageal cancer within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
• a. Patients who received endoscopic mucosal resection or dissection for superficial mucosal cancers other than ESCC within 2 years prior to screening are eligible for the study.
• Prior organ transplantation including allogenic stem-cell transplantation
• Current use of immunosuppressive medication, EXCEPT for the following:
• intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
• systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent
• steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Treatment with therapeutic oral or intravenous antibiotics within 2 weeks prior to registration
• a. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment and on stable regimen are eligible.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

RECRUITING

MeSH Terms

Interventions

Tiragolumab; atezolizumab; Paclitaxel; Cisplatin; Radiotherapy; Surgical Procedures, Operative

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Officials

• Chia-Hsien Cheng, Cheng

  Employee

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chia-Hsien Cheng, c

CONTACT

+886-2-2352-2846; jasoncheng@ntu.edu.tw

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 24, 2023
• Study Start: September 18, 2023
• Primary Completion: May 31, 2025
• Study Completion: November 30, 2025
• Last Updated: February 2, 2024

Record last verified: 2023-09

Locations

TW (1)