Radiotherapy Plus Durvalumab in Elderly Esophageal Squamous Cell Carcinoma

Radiotherapy Plus Durvalumab in Elderly Esophageal Squamous Cell Carcinoma: A Prospective Phase II Clinical Trial

The incidence and mortality of esophageal cancer are at the forefront in China, among which the elderly patients account for a large proportion. Concurrent chemoradiotherapy is the standard treatment for inoperable locally advanced esophageal cancer. Most elderly patients with esophageal cancer cannot tolerate concurrent chemotherapy because of complications and other reasons. Immunotherapy has definite efficacy and low toxicity in advanced esophageal squamous cell carcinoma, and the results combined with radiotherapy have also been preliminarily reported. Therefore, it is necessary to further explore the efficacy and safety of radiotherapy combined with immunotherapy in elderly patients with esophageal cancer.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Radiation: Radiotherapy; Drug: Durvalumab

• Study Type: Interventional
• Enrollment (Anticipated): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • Recruiting
    • National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 70-85 years old, both men and women
2. Histologically confirmed esophageal squamous cell carcinoma located in thoracic segment, treatment naive
3. Stage cT2-4aNanyM0 (AJCC 8 TNM classification)
4. Unresectable, unable to tolerate or refuse surgery and concurrent chemoradiotherapy
5. ECOG PS 0-2
6. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
7. No severe abnormalities of the Hematologic system, heart, lung, liver, kidney, and immunodeficiency

8. Adequate bone marrow and organ function as defined below (excluding the use of any blood components and cell growth factors within 7 days):

   • Absolute neutrophil count≥1,500/mm3
   • Platelets ≥ 100,000/mm3
   • Hemoglobin ≥ 5.6 mmol/L (9g/dL)
   • Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥50 mL/min by Cockcroft-Gault estimation
   • Total bilirubin ≤ 1.5 x ULN
   • ALT and AST ≤ 2.5 x ULN
   • Proteinuria < 2+, for subjects with urine protein ≥ 2 + at baseline, urine samples should be collected within 24 hours and urine protein in 24 hours should be ≤ 1g
9. INR or PT or aPTT ≤ 1.5 x ULN
10. Life expectancy more than 6 months
11. Ability to understand and willingness to sign an IRB approved written informed consent document, and capable of proper therapeutic compliance, and accessible to correct follow-up

Exclusion Criteria:

1. Complete esophageal obstruction that unable to eat fluid and cannot provide necessary nutrition through nasal feeding
2. Patients with obvious ulcer or esophageal perforation or hematemesis
3. Placement of esophagotracheal stents
4. Has a history or current evidence of pulmonary fibrosis, interstitial pneumonia, pneumonoconiosis, drug-associated pneumonia, severe impairment of pulmonary function
5. Has had major surgery within 28 days prior to the start of the treatment
6. Immunosuppressive drugs used within 4 weeks prior to the initial study treatment, excluding local glucocorticoids, or systemic glucocorticoids at physiological doses (i.e., no more than 10 mg/ day of prednisone or equivalent doses of other glucocorticoids);
7. The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, glomerulonephritis, thyroiditis (patients with vitiligo or asthma has been completely relieved in childhood, and do not need any intervention during adulthood can be included; patients with type I diabetes with good insulin control can also be included; hypothyroidism caused by autoimmune thyroiditis requiring hormone replacement therapy can also be included)
8. Has had congenital or acquired immunodeficiency, such as human immunodeficiency virus (HIV) infection, active hepatitis B (HBV-DNA ≥ 104 copies/ml) or hepatitis C (HCV-RNA ≥ 103 copies/ml; For chronic hepatitis B virus carriers, HBV viral load must be < 2000 IU/ml (< 104 copies / ml), and must receive antiviral therapy at the same time before they can be enrolled
9. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation
10. Uncontrolled clinically significant disease, including active infection, uncontrolled hypertension, unstable angina pectoris, angina within the past 3 months, heart failure > NYHA II, myocardial infarction within the past 6 months, severe arrhythmias requirement for treatment or intervention, liver/kidney or metabolic disease
11. System infections that require treatment
12. Received a live vaccine within 4 weeks of the first dose of study medication
13. Synchronous or metachronous second primary malignancy. Participants with basal cell carcinoma of the skin, or cervical cancer in situ that have undergone potentially curative therapy are not excluded from the study
14. Patients who have participated in other clinical trials within 30 days
15. Drug addiction, chronic alcoholism and AIDS
16. Patients with uncontrollable seizures or loss of self-control due to mental illness
17. Those with a history of severe allergy or specific physique
18. The investigators judge not suitable for inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exprimental Arm; IMRT plus Durvalumab	Radiation: Radiotherapy; IMRT (Intensity Modulated RT) or 3D-CRT (three-dimensional conformal radiotherapy); 95% PGTV 59.92Gy/2.14Gy/28f; 95% GTVnd 59.92Gy/2.14Gy/28f; 95% PTV 50.40Gy/1.80Gy/28f; 5 days a week; 6 weeks.; Drug: Durvalumab; Durvalumab 1000 mg, intravenously (IV), on Day 1 of radiotherapy, every 3 weeks for up to 18 administrations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS was assessed by Response Evaluation Criteria in Solid Tumors (RECIST)1.1. Progression-free survival defined as the time from enrollment to the first documented disease progression of local recurrence or distant metastasis or death due to any cause.	1-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall survival defined as the time from enrollment to death due to any cause.	1-, 2- and 3-year
Progression-free survival (PFS)	PFS was assessed by Response Evaluation Criteria in Solid Tumors (RECIST)1.1. Progression-free survival defined as the time from enrollment to the first documented disease progression of local recurrence or distant metastasis or death due to any cause.	2- and 3-year
Objective Response Rate (ORR)	ORR was Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).	during the intervention up to 60 weeks
Disease Control Rate (DCR)	DCR was Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).	during the intervention up to 60 weeks
Number of participants with an adverse event	Evaluanted by CTCAE 5.0	Up to 60 weeks
Quality of Life (QOL): questionnaire EORTC QLQ-C30 (version 3)	Evaluate the quality of life via questionnaire EORTC QLQ-C30 (version 3), minimum value 30, maximum value 126, higher scores mean a worse outcome.	up to 60 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life (QOL): questionnaire EORTC QLQ-OES18	Evaluate the quality of life via questionnaire EORTC QLQ-OES18, minimum value 18, maximum value 72, higher scores mean a better outcome.	up to 60 weeks

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2021
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: April 5, 2021
• First Submitted That Met QC Criteria: April 16, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): June 22, 2021
• Last Update Submitted That Met QC Criteria: June 20, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: NCC2840

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No