Combination of Tislelizumab and Chemoradiotherapy in Esophageal Cancer (EC-CRT-002)

NCT ID: NCT05520619

Last Updated: 2024-11-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-15
• Study Completion Date: 2026-07-31

Brief Summary

Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable locally advanced esophageal cancer (EC). However, as high as more than 40% of EC patients experienced locoregional recurrence after concurrent CRT. Immunotherapy targeting the PD-1/PD-L1 checkpoints has demonstrated promising activity in advanced EC. Recently, the combination of immunotherapy with CRT has emerged as a promising strategy to improve clinical outcomes in EC. The aim of this study was to evaluate whether the efficacy of tislelizumab (an anti-PD-1 antibody) plus induction chemotherapy followed by concurrent chemoradiotherapy would achieve a ≥71% 1-year progression-free survival rate, surpassing the historical 56% rate (NCT02403531) in patients with locally advanced esophageal squamous cell carcinoma (ESCC).

Detailed Description

A total of 114 patients with unresectable, locally advanced ESCC will be randomized to receive either tislelizumab plus induction chemotherapy followed by concurrent CRT and then 12 additional cycles of tislelizumab (Arm A) or tislelizumab plus the same induction and concurrent regimen without the maintenance of tislelizumab (Arm B).

Patients will receive 2 cycles of 3-weekly schedule of induction chemotherapy, consisting of paclitaxel 135-175 mg/m2, cisplatin 75 mg/m2, and tislelizumab 200mg on day 1 prior to CRT. Then all patients will receive standard fractionation radiation therapy scheme: 50.4 Gy in 28 fractions, concurrently with paclitaxel 45mg/m2 and cisplatin 25 mg/m2 once weekly for 5 weeks and 2 cycles of tislelizumab. Patients in Arm A will receive 12 additional cycles of tislelizumab after the completion of CRT.

Conditions

Esophageal Squamous Cell Carcinoma; Locally Advanced Esophageal Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tislelizumab plus CRT with maintenance

Patients will receive 2 cycles of 3-weekly schedule of induction chemotherapy, consisting of paclitaxel 135-175 mg/m2, cisplatin 75 mg/m2, and tislelizumab 200mg on day 1 prior to CRT. Then all patients will receive standard fractionation radiation therapy scheme: 50.4 Gy in 28 fractions, concurrently with paclitaxel 45mg/m2 and cisplatin 25 mg/m2 once weekly for 5 weeks and 2 cycles of tislelizumab. Patients in Arm A will receive 12 additional cycles of tislelizumab after the completion of radiotherapy.

Group Type: EXPERIMENTAL

Paclitaxel, Cisplatin

Intervention Type: DRUG

Patients received 2 cycles of induction chemotherapy with paclitaxel/cisplatin (paclitaxel 135-175mg/m2 and cisplatin 75 mg/m2) prior to radiotherapy. Then patients will receive paclitaxel 45mg/m2 and cisplatin 25 mg/m2 once weekly for 5 weeks during radiotherapy.

tislelizumab

Intervention Type: DRUG

Patients received tislelizumab 200 mg every 3 weeks for 16 cycles in Arm A and 4 cycles in Arm B.

Radiotherapy

Intervention Type: RADIATION

All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 50.4 Gy in 28 fractions over 5-6 weeks.

Tislelizumab plus CRT without maintenance

Patients will receive 2 cycles of 3-weekly schedule of induction chemotherapy, consisting of paclitaxel 135-175 mg/m2, cisplatin 75 mg/m2, and tislelizumab 200mg on day 1 prior to CRT. Then all patients will receive standard fractionation radiation therapy scheme: 50.4 Gy in 28 fractions, concurrently with paclitaxel 45mg/m2 and cisplatin 25 mg/m2 once weekly for 5 weeks and 2 cycles of tislelizumab. Patients in Arm B will receive 4 cycles of tislelizumab in total.

Group Type: EXPERIMENTAL

Paclitaxel, Cisplatin

Intervention Type: DRUG

Patients received 2 cycles of induction chemotherapy with paclitaxel/cisplatin (paclitaxel 135-175mg/m2 and cisplatin 75 mg/m2) prior to radiotherapy. Then patients will receive paclitaxel 45mg/m2 and cisplatin 25 mg/m2 once weekly for 5 weeks during radiotherapy.

tislelizumab

Intervention Type: DRUG

Patients received tislelizumab 200 mg every 3 weeks for 16 cycles in Arm A and 4 cycles in Arm B.

Radiotherapy

Intervention Type: RADIATION

All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 50.4 Gy in 28 fractions over 5-6 weeks.

Interventions

Paclitaxel, Cisplatin

Patients received 2 cycles of induction chemotherapy with paclitaxel/cisplatin (paclitaxel 135-175mg/m2 and cisplatin 75 mg/m2) prior to radiotherapy. Then patients will receive paclitaxel 45mg/m2 and cisplatin 25 mg/m2 once weekly for 5 weeks during radiotherapy.

Intervention Type: DRUG

tislelizumab

Patients received tislelizumab 200 mg every 3 weeks for 16 cycles in Arm A and 4 cycles in Arm B.

Intervention Type: DRUG

Radiotherapy

All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 50.4 Gy in 28 fractions over 5-6 weeks.

Intervention Type: RADIATION

Other Intervention Names

Taxol; intensity-modulated radiotherapy

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed squamous cell carcinoma of the esophagus;

2. Locally advanced, and absence of hematogenous metastasis disease, confirmed by endoscopic ultrasound (EUS) and PET-CT scan (according to UICC TNM version 8);

3. Not suitable for surgery (either for medical reasons or patient's choice);

4. Age at diagnosis 18 to 70 years;

5. No prior cancer therapy;

6. Estimated life expectancy >6 months;

7. Eastern Cooperative Oncology Group performance status ≤ 2

8. No history of concomitant or previous malignancy;

9. The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥4.0×109/L, absolute neutrophil count (ANC) ≥1.5×109/L; b. platelets ≥100×109/L; c. hemoglobin ≥9g/dL; d. serum albumin ≥2.8g/dL; e. total bilirubin ≤1.5×ULN, ALT, AST and/or AKP ≤2.5×ULN; f. serum creatinine ≤1.5×ULN or creatinine clearance rate >60 mL/min;

10. Ability to understand the study and sign informed consent.

Exclusion Criteria

1. Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);

2. Patients with hematogenous metastasis disease at diagnosis;

3. Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of Toripalimab, and the chemotherapeutic drugs paclitaxel or cisplatin;

4. Patients who have a preexisting or coexisting bleeding disorder;

5. Female patients who are pregnant or lactating;

6. Inability to provide informed consent due to psychological, familial, social and other factors;

7. Presence of CTC grade ≥ 3 peripheral neuropathy;

8. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer

9. A history of diabetes for more than 10 years and poorly controlled blood glucose levels;

10. Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.

11. Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), a history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation;

12. A history of interstitial lung disease or non-infectious pneumonia;

13. A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment;

14. Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Zhongshan People's Hospital, Guangdong, China

OTHER

Sponsor Role: collaborator

Jieyang People's Hospital

OTHER

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Mian XI

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ruihua Xu, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Mian Xi

Guangzhou, Guangdong, China

Countries

China

References

Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Oliden VC, Liu Q, Shah S, Bhagia P, Kato K; KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4.

Reference Type: BACKGROUND

PMID: 34454674 (View on PubMed)

Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, Zhang Y, Zhao K, Chen Z, Gao S, Li J, Fu Z, Gu K, Liu Z, Wu L, Zhang X, Feng J, Niu Z, Ba Y, Zhang H, Liu Y, Zhang L, Min X, Huang J, Cheng Y, Wang D, Shen Y, Yang Q, Zou J, Xu RH; ESCORT-1st Investigators. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial. JAMA. 2021 Sep 14;326(10):916-925. doi: 10.1001/jama.2021.12836.

Reference Type: BACKGROUND

PMID: 34519801 (View on PubMed)

Other Identifiers

SL-B2022-216-02

Identifier Type: -

Identifier Source: org_study_id