Clinical trial NCT06084897: Radiotherapy in Patients With Metastatic Esophageal Cancer Responding to PD-1 Inhibitor Plus Chemotherapy
Official title: Radiotherapy in Patients With Metastatic Esophageal Cancer Responding to PD-1 Inhibitor Plus Chemotherapy: a Patient Preference Multicenter Randomized Phase II Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Esophageal Neoplasm Metastatic
Esophageal Cancer Stage IVb
Lead sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Sponsor class: OTHER
Collaborators: name: Peking University Cancer Hospital & Institute
name: Hebei Medical University Fourth Hospital
name: Tianjin Medical University Cancer Institute and Hospital
name: Anyang Tumor Hospital
First posted: 2023-10-16
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 II clinical trial to assess whether radiotherapy could further improve the survival of patients with metastatic esophageal cancer responding to PD-1 Inhibitor plus chemotherapy.

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.

Detailed 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 metastatic EC.

As reported, for the patients with metastatic lung cancer or EC, locoregional radiotherapy could improve survival, especially in those who responding to systemic therapy. 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 those patients with metastatic EC responding to systemic therapy improve local control, relieve the local symptoms, and even improve survival.

Therefore, the investigators intend to conduct a prospective, multicenter phase II trial to assess the efficiency and safety of radiotherapy with chemotherapy and immunotherapy for 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.

Eligibility criteria: 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 AJCC Cancer Staging Manual, 8th Edition) or recurrent patients with recurrence after radical treatment (radical treatment includes surgery and radiotherapy, but the recurrence site cannot be located in the previous radiotherapy field).
* 3. ECOG performance 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.For patients after definitive or preoperative radiotherapy, no recurrence was in the prior radiation filed;
* 6.Expected survival is more than 12 weeks;
* 7.Informed consent provided;
* 8.With response to 2-4 cycles of the first-line chemotherapy combined with immunotherapy.

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.

Primary outcomes:
measure: EFFICACY:1-year overall survival probability
timeFrame: 12 month
Secondary outcomes:
measure: EFFICACY: Median progression-free survival (PFS)
timeFrame: 12 month
measure: SAFETY: Acute toxicity rate
timeFrame: One month within the end of one specific treatment
measure: SAFETY: Late toxicity rate
timeFrame: One month after the end of one specific treatment.
measure: QUALITY OF LIFE: Change From Baseline in the EORTC QLQ-C30 Subscale Scores in Participants
timeFrame: 24 month
measure: QUALITY OF LIFE: Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants
timeFrame: 24 month
Other outcomes:
measure: Biomarkers for the predicting of efficacy
timeFrame: 24 month
Locations:
city: Beijing
country: China
facility: Cancer hospital, CAMS
state: Beijing
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Wen-Yang Liu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking University Cancer Hospital & Institute
name: Zhi-Hao Lu, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.