Phase II Study of Concurrent Radiotherapy With Envafolimab and Capecitabine in LAPC

Phase II Study of Concurrent Radiotherapy With Envafolimab and Capecitabine in Locally Advanced Pancreatic Cancer

This is a single-arm prospective phase II clinical trial to investigate the efficacy and safety of concurrent radiotherapy with envafolimab and capecitabine in locally advanced pancreatic cancer.Eligibility patients will receive intensity-modulated radiotherapy(IMRT)or volumetric modulated arc therapy(VMAT) to pancreatic lesions,metastatic lymph nodes and high-risk lymphatic drainage areas,concurrent with and followed by envafolimab and capecitabine.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; Capecitabine; Radiotherapy; Envafolimab
• Intervention / Treatment: Radiation: concurrent radiotherapy with envafolimab and capecitabine

Detailed Description

This is a single-arm prospective phase II clinical trial to investigate the efficacy and safety of concurrent radiotherapy with envafolimab and capecitabine in locally advanced pancreatic cancer.Primary enrollment criteria is locally advanced non-resectable pancreatic cancer without systemic metastases other than retroperitoneal lymph nodes.Eligibility patients will receive intensity-modulated radiotherapy(IMRT)or volumetric modulated arc therapy(VMAT) to pancreatic lesions,metastatic lymph nodes and high-risk lymphatic drainage areas,concurrent with and followed by envafolimab and capecitabine.Concurrent and sequential dose of envafolimab is 200mg subcutaneous injection weekly.Capecitabine is with a concurrent and sequential dose of 500-800 mg/m2 bid po , taken orally for 2 weeks and stopped for 1 week (standard concurrent dose is 800 mg/m2 bid po , but for patients ≥70 years of age, 500 mg/m2 bid po depending on physical status ) until progression or intolerance.

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bo Chen, MD; Phone Number: 008613240000876; Email: cbchinese@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Bo Chen
      • Contact: Bo Chen, MD; Phone Number: 008613240000876; Email: chenboo@outlook.com
      • Principal Investigator: Bo Chen, MD
      • Sub-Investigator: Yirui Zhai, MD
      • Sub-Investigator: Zhuanbo Yang, MD
      • Sub-Investigator: Pan Zhao, BA
      • Sub-Investigator: Yuan Zong, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: 18-90 years old.
2. Pancreatic cancer diagnosed by histology or cytology.
3. Locally or regionally advanced non-resectable pancreatic cancer without systemic metastases other than retroperitoneal lymph nodes.
4. Patients who have not received prior systemic chemotherapy or who have progressed on first-line therapy.
5. At least one measurable lesion (≥10 mm long diameter on CT scan for tumor lesions and ≥15 mm short diameter on CT scan for lymph node lesions according to RECIST 1.1 criteria).
6. ECOG score: 0-1.
7. Expected survival ≥ 3 months.
8. Normal function of major organs, meeting the following criteria:

9. Criteria for routine blood tests need to be met (no blood and blood products transfusion within 14 days):

   1. ANC ≥ 1.5×10^9/L
   2. PLT ≥80×10^9/L

10. Biochemical tests need to meet the following criteria:

    1. TBIL<1.5 ULN
    2. ALT and AST < 2.5ULN and in patients with liver metastases < 5ULN
    3. Serum Cr ≤ 1.25ULN or endogenous creatinine clearance > 45 ml/min (Cockcroft-Gault formula) 11).Subjects voluntarily enrolled in this study and signed an informed consent form, were compliant and cooperated with the follow-up.

Exclusion Criteria:

1. Presence of any active autoimmune disease or history of autoimmune disease in the subject.
2. Allergy to study-used medications.
3. Subjects who are on immunosuppressive, or systemic, or absorbable topical hormone therapy for immunosuppression (dose >10mg/day prednisone or other equipotent hormone) and who continue to be on it within 2 weeks prior to enrollment.
4. Class III-IV cardiac insufficiency according to NYHA criteria, or cardiac ultrasound suggesting left ventricular ejection fraction (LVEF) <50%.
5. Those with abnormal coagulation function (INR>1.5,APTT>1.5 ULN) and bleeding tendency.
6. prolonged unhealed wounds or fractures; major surgical procedures or severe traumatic injuries, fractures or ulcers within 4 weeks.
7. Subjects with congenital or acquired immune deficiency (e.g., HIV-infected individuals), or active hepatitis (Hepatitis B reference: HBV DNA test value exceeding the upper limit of normal, Hepatitis C reference: HCV viral titer or RNA test value exceeding the upper limit of normal).
8. Subject has received other prior PD-1 antibody immunotherapy or other immunotherapy targeting PD-1 or PD-L1.
9. Known existing hereditary or acquired bleeding and thrombotic tendencies (e.g., hemophiliacs, coagulation disorders, thrombocytopenia, hypersplenism, etc.) or events of arterial or venous thrombosis in the last 6 months (up to the first medication use of envafolimab ).
10. Subjects with active infection or unexplained fever >38.5 degrees Celsius during screening and prior to the first dose.
11. Patients with central nervous system metastases;
12. Subjects who have had a live bacterial vaccine or live attenuated vaccine vaccine within 30 days prior to the first dose of study treatment.
13. Subjects with previous or concurrent other malignant tumors.
14. Women who are pregnant or breastfeeding.
15. Those with a history of psychotropic substance abuse that cannot be abstained from or patients with psychiatric disorders.
16. Patients with concomitant illnesses that, in the judgment of the investigator, seriously jeopardize patient safety or interfere with the patient's ability to complete the study.
17. Those who are not suitable for inclusion in the judgment of the investigator.

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: Concurrent Radiotherapy With Envafolimab and Capecitabine; Concurrent radiotherapy with envafolimab and capecitabine, post-adjuvant envafolimab and capecitabine for locally advanced pancreatic cancer

Radiation: concurrent radiotherapy with envafolimab and capecitabine; Eligibility patients will receive intensity-modulated radiotherapy(IMRT)or volumetric modulated arc therapy(VMAT) to pancreatic lesions,metastatic lymph nodes and high-risk lymphatic drainage areas,concurrent with and followed by envafolimab and capecitabine.Concurrent and sequential dose of envafolimab is 200mg subcutaneous injection weekly.Capecitabine is with a concurrent and sequential dose of 500-800 mg/m2 bid po , taken orally for 2 weeks and stopped for 1 week (standard concurrent dose is 800 mg/m2 bid po , but for patients ≥70 years of age, 500 mg/m2 bid po depending on physical status ) until progression or intolerance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Overall Response Rate (ORR) was defined as the total of CR (Complete Response) and PR (Partial Response). CR and PR were assessed by independent reviewers according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. ORR evaluated in 1 to 3 months after the completion of radiotherapy.	1-3 months after radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progress free survival	up to 24 months
OS	Overall Survival (OS) was defined as the duration from the date of patient recruited to the date of death with any reason	up to 24 months
DCR	Complete response(CR)and partial response(PR)	up to 24 months
DoR	During of response	up to 24 months
Incidence of grade 3 and above adverse events	Adverse events was evaluated during received protocol therapy according to the NCI Common Terminology Criteria for Adverse Events 4.03(CTCAE 4.03).	up to 24 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): January 31, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 2, 2024
• First Submitted That Met QC Criteria: January 2, 2024
• First Posted (Actual): January 11, 2024

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: capecitabine; radiotherapy; pancreatic cancer; envafolimab
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: NCC4325

Drug and device information, study documents

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