PD-1 Inhibitor Plus Chemotherapy With or Without Radiotherapy in Patients With Metastatic Esophageal Cancer

Esophageal Neoplasms Clinical Trial

Official title:

PD-1 Inhibitor Plus Chemotherapy With or Without Radiotherapy in Patients With Metastatic Esophageal Cancer: A Randomized Multicenter Phase III Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06086457
• Other study ID #: BEIR 0
• Status: Recruiting
• Phase: Phase 3
• Start date: February 4, 2024
• Est. completion date: August 28, 2029

Study information

• Verified date: April 2023
• Source: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Contact: Wen-Yang Liu, MD
• Phone: 8601087787625
• Email: liuwenyang[@]cicams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The treatment efficacy for stage IVb esophageal cancer has been improved through chemotherapy combined with immunotherapy recently. On this basis, the investigators intend to conduct a prospective, multicenter phase III clinical trial to assess whether radiotherapy with concurrent chemotherapy and immunotherapy could further improve the survival of patients with metastatic esophageal cancer. Accompanied tissue samples, blood samples and urine samples will be analyzed by molecular biological detection (Including Whole Exome Sequencing and proteomics) to explore potential biomarkers for predicting outcomes, efficacy and toxicity.

Description:

Esophageal cancer (EC) is one of the most common carcinomas with high morbidity and mortality worldwide. More than 30% of the patients were stage IV when diagnosed. Fluoropyrimidine plus platinum-based chemotherapy is recommended as first-line treatment for patients with metastatic EC for approximately four decades, however, only minimal improvement has been reached in overall survival (OS). Recently, immune checkpoint inhibitors have shown effective antitumor activity in patients with unresectable, advanced or metastatic EC. Several randomized trials have demonstrated the PD-1 inhibitor could further improve the OS in patients with advanced esophageal squamous cell carcinoma (ESCC) on the basis of chemotherapy. Chemotherapy combined with immunotherapy has become one of the the standard treatment modality for advanced EC. As reported, for the patients with metastatic lung cancer or EC, locoregional radiotherapy could improve survival. However, high-level evidence is still needed to assess whether these patients can benefit from local radiotherapy. The efficacy of immunotherapy combined with chemotherapy is obviously better than that of chemotherapy alone. On this basis, locoregional radiotherapy may help some patients with advanced EC improve local control, relieve the local symptoms and improving the quality of life. Therefore, the investigators intend to conduct a prospective, multicenter phase III trial to assess the efficiency and safety of radiotherapy with chemotherapy and immunotherapy of patients with metastatic EC. Accompanied tissue samples, blood samples and urine samples will be analyzed by molecular biological detection to explore potential biomarkers for predicting outcomes, efficacy and toxicity.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 436
• Est. completion date: August 28, 2029
• Est. primary completion date: June 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1. =18 years, any gender
• 2. Histologically or cytologically confirmed squamous cell carcinoma of esophageal cancer. The initial clinical stage is IVb (2018 American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th Edition) , with distant metastasis involving no more than 2 organs (lymph node metastasis is counted);
• 3. ECOG (Eastern Cooperative Oncology Groupper) formance status <= 1. Patients aged 65 years and over need to complete G8 screening or Comprehensive Geriatric Assessment, and the final evaluation is good;
• 4.There was no significant abnormality in laboratory routine indicators such as blood routine and liver and kidney function;
• 5.No prior history of thoracic radiation;
• 6.Expected survival is more than 12 weeks;
• 7.Informed consent provided.

Exclusion Criteria:

• 1.Patients with other cancer history except hypopharyngeal carcinoma in situ, non-malignant skin cancer and cervical carcinoma in situ.
• 2.Received surgery (except ostomy), chemotherapy or other anti-tumor treatment before enrollment;
• 3. Active infection currently exists . The following conditions occurred within 6 months before randomization: myocardial infarction, cerebrovascular accident, or received gastrointestinal, neurological, cardiopulmonary surgery;
• 4. History of allergy to chemotherapy drugs or autoimmune disease;
• 5. Participate in other clinical trials at present or within 4 weeks before enrollment;
• 6.There are factors such as high risk of fistula that radiotherapy cannot be safely carried out as assessed by the radiation oncologist.

Related Conditions & MeSH terms

• Esophageal Neoplasms

Intervention

Radiation:
• Radiation
IMRT/VMAT technique. Patients receive radiotherapy once daily, 5 days a week for an average of 5 weeks. Radiotherapy is delivered to achieve a dosage of 50Gy in 25 fractions to planning gross tumor volume (PGTV) with involved site included.

Drug:
• TP or PF regimen depended on investigator's choice.
A maximum of six cycles was recommended for chemotherapy. Chemotherapy Regimen 1(TP regimen A): Nab-paclitaxel(Albumin-bound paclitaxel) 110-130mg/ m2,d1,d8; Cisplatin 60-75mg/ m2,d1;Q3W; Chemotherapy Regimen 2 (TP regimen B): Paclitaxel 150-175 mg/m2, d1; Cisplatin 60-75mg/ m2,d1;Q3W; PD-1 inhibitor 200mg, d1, Q3W Chemotherapy Regimen 3 (PF regimen): Capecitabine 800mg/m2, bid, d1-14; Cisplatin 25-30mg/m2, d1,d2, Q3W.

Biological:
• PD-1 inhibitor
Camrelizumab (200mg, d1, Q3W) was continued until disease progression, unacceptable toxicity, death, physician or patient decision to withdraw, non-compliance, or discontinuation for administrative reasons (up to 35 cycles).

Locations

Country	Name	City	State
China	Cancer hospital, CAMS	Beijing	Beijing

Sponsors (17)

Lead Sponsor

Collaborator

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Af?liated Hospital of North Sichuan Medical College, Anyang Tumor Hospital, Beijing Cancer Prevention & Treatment Society, Changzhou Cancer Hospital of Soochow University, First Affiliated Hospital Xi'an Jiaotong University, Fujian Cancer Hospital, Hebei Medical University Fourth Hospital, Henan Cancer Hospital, Peking University Cancer Hospital & Institute, Second Affiliated Hospital of Xi'an Jiaotong University, Sichuan Cancer Hospital and Research Institute, Tengzhou Central People's Hospital, The First Affiliated Hospital of Xiamen University, The First Affiliated Hospital of Zhengzhou University, The First Affiliated Hospital with Nanjing Medical University, Tianjin Medical University Cancer Institute and Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

Guttmann DM, Mitra N, Bekelman J, Metz JM, Plastaras J, Feng W, Swisher-McClure S. Improved Overall Survival with Aggressive Primary Tumor Radiotherapy for Patients with Metastatic Esophageal Cancer. J Thorac Oncol. 2017 Jul;12(7):1131-1142. doi: 10.1016/j.jtho.2017.03.026. Epub 2017 Apr 28. — View Citation

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. — View Citation

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. Erratum In: Lancet. 2021 Nov 20;398(10314):1874. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biomarkers for the predicting of efficacy	To explore the dynamic changes of circulating tumor DNA (the frequency of specific mutations by Next-generation sequencing Methodology) from baseline, before and after radiotherapy.	33 months
Primary	Overall survival (OS)	Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS is reported for all participants of the Intent-To-Treat (ITT) population (all randomized).	Up to approximately 33 months (through Primary Analysis cut-off date of 30-May-2026).
Secondary	Progression-free survival (PFS)	PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first.	Up to approximately 33 months (through Primary Analysis cut-off date of 30-May-2026).
Secondary	Objective Response Rate (ORR)	ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: =30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator.	Up to approximately 33 months (through Primary Analysis cut-off date of 30-May-2026).
Secondary	Acute toxicity Rate	Acute toxicity rate was defined as the frequency of toxicities related to the treatment, which arises within one month after administration, according to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 5.0 (CTC Adverse Event 5.0).	One month within the end of one specific treatment.
Secondary	Late toxicity rate	Late toxicity rate was defined as the frequency of toxicities related to the treatment, which arises after one month after administration, according to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 5.0 (CTC Adverse Event 5.0).	One month after the end of one specific treatment.
Secondary	QUALITY OF LIFE: Change From Baseline in the EORTC QLQ-C30 Subscale Score in Participants	The score of the participants evaluated by The EORTC core quality of life questionnaire (QLQ-C30) . The scale and single-item measure range in score from 0 to100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high/healthy level of functioning.	24 months
Secondary	QUALITY OF LIFE: Change From Baseline in the EORTC QLQ-OES18 Subscale Score in Participants	The score of the participants evaluated by The EORTC Quality of Life Questionnaire - Oesophageal Cancer Module (EORTC QLQ-OES18). The scale and single-item measure range in score from 0 to100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high/healthy level of functioning.	24 months