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

NCT06086457 | Recruiting Phase 3 DMC

• 1 other identifier: BEIR 0
• Study Type: interventional
• Target: 436
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Esophageal Neoplasms

Keywords

Radiotherapy; PD-1 inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Progression-free survival (PFS)

  Up to approximately 33 months (through Primary Analysis cut-off date of 30-May-2026).

• Objective Response Rate (ORR)

  Up to approximately 33 months (through Primary Analysis cut-off date of 30-May-2026).

• Acute toxicity Rate

  One month within the end of one specific treatment.

• Late toxicity rate

  One month after the end of one specific treatment.

• QUALITY OF LIFE: Change From Baseline in the EORTC QLQ-C30 Subscale Score in Participants

  24 months

Other Outcomes (1)

• Biomarkers for the predicting of efficacy

  33 months

Study Arms (2)

PD-1 inhibitor plus chemotherapy arm

ACTIVE COMPARATOR

Drugs: TP or PF regimen depended on investigator's choice. A maximum of six cycles was recommended for chemotherapy. Biological: PD-1 inhibitor (Camrelizumab).

Drug: TP or PF regimen depended on investigator's choice.; Biological: PD-1 inhibitor

Radiotherapy arm

EXPERIMENTAL

Radiation: Intensity-modulated Radiation Therapy/Volumetric Modulated Arc Therapy (IMRT/VMAT) technique. Patients will receive radiotherapy between the first and third cycle of chemotherapy. Drugs: TP or PF regimen depended on investigator's choice. Biological: PD-1 inhibitor (Camrelizumab).

Radiation: Radiation; Drug: TP or PF regimen depended on investigator's choice.; Biological: PD-1 inhibitor

Interventions

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.

Also known as: Modern intensity modulated radiotherapy

Radiotherapy arm

TP or PF regimen depended on investigator's choice. DRUG

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.

Also known as: Chemotherapy

PD-1 inhibitor plus chemotherapy arm; Radiotherapy arm

PD-1 inhibitor BIOLOGICAL

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).

Also known as: Camrelizumab

PD-1 inhibitor plus chemotherapy arm; Radiotherapy arm

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: gender identity
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. ≥18 years, any gender
• \. 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);
• \. 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;
• There was no significant abnormality in laboratory routine indicators such as blood routine and liver and kidney function;
• No prior history of thoracic radiation;
• Expected survival is more than 12 weeks;
• Informed consent provided.

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (1)

Cancer hospital, CAMS

Beijing, Beijing Municipality, 100021, China

RECRUITING

Related Publications (3)

• 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.

  PMID: 34454674 BACKGROUND

• 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.

  PMID: 34519801 BACKGROUND

• 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.

  PMID: 28461255 BACKGROUND

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Radiation; Drug Therapy; Immune Checkpoint Inhibitors; camrelizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Phenomena; Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Lin Shen, MD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

• Wen-Yang Liu, MD

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wen-Yang Liu, MD

CONTACT

8601087787625; liuwenyang@cicams.ac.cn

Zhi-Hao Lu, MD

CONTACT

86-10-88196561; pppeirain@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2023
• First Posted: October 17, 2023
• Study Start: February 4, 2024
• Primary Completion (Estimated): June 28, 2026
• Study Completion (Estimated): August 28, 2029
• Last Updated: July 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data requests can be submitted starting 12 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact liuwenyang@cicams.ac.cn

Locations

CN (1)