A Multi Tumor, Open Phase I Clinical Study on the Progression of First-line Anti-tumor Therapy Using Cardonizumab Combined With Pulsed Low-dose Rate External Irradiation (PLDR)

NCT06232083 | Recruiting Phase 1 DMC

• 1 other identifier: Zhou peijie-2024ky-05
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

At present, the treatment methods for recurrent cancers are very limited. The immune checkpoint inhibitors (ICBs) is a promising new directions for recurrent lung cancer/ esophageal cancer / cervical cancer, but the clinical response rate is insufficient. Pulse low-dose rate radiotherapy (PLDR) is a new technology in recent years, which uses continuous pulse low-dose rate irradiation to induce hypersensitivity in tumors, and its clinical safety has been verified. Compared to conventional radiotherapy, PLDR has advantages in protecting the lymphatic system and relieving the immune barrier, but it is still unclear whether it can improve the efficacy of ICB. This project aims to combine PLDR with ICB to explore new strategies for recurrent patients.

Conditions

Lung Cancer; Esophageal Cancer; Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• ORR

  Objective response rate，The proportion of patients whose tumor volume shrinks by 30% and can be maintained for more than four weeks, which is the sum of complete remission and partial remission (CR+PR)

  6 month post PLDR external irradiation

Secondary Outcomes (1)

• TEAE

  6 month post PLDR external irradiation

Study Arms (1)

PLDR+Cadonilimab

EXPERIMENTAL

1. PLDR: 40Gy/20f; GTV is the recurrence or metastasis lesion with clear imaging (the radiotherapy lesion is determined by the researcher, and the first-line treatment is preferred for the advanced lesion). CTV is the appropriate expansion of GTV by 0.5cm-0.7cm, including the related lymphatic drainage area (such as neck and pelvic cavity) if necessary. 2. ICB was performed during the external irradiation of PLDR, and cadunizumab 6mg/kg was given for 2 weeks; After the external irradiation of PLDR, cardunilimab was maintained at the dose of 10mg/kg for 3 weeks. Maintenance treatment for 2 years.

Radiation: PLDR+Cardunizumab

Interventions

PLDR+Cardunizumab RADIATION

Application of PLDR external irradiation combined with Cardunizumab in recurrent lung cancer, esophageal cancer and cervical cancer.

PLDR+Cadonilimab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all the following criteria to be enrolled:
• The subjects voluntarily joined the study, signed informed consent, had good compliance and were willing to cooperate with the follow-up;
• There is no limit for men and women, ranging in age from 18 to 75 years old (including 18 and 75 years old);
• Pathologically confirmed esophageal cancer, lung cancer or cervical cancer;
• The expected survival time was more than 3 months;
• Recurrent or metastatic patients with previous treatment progress;
• ECoG 0-2 points;
• According to RECIST 1.1 standard, there was at least one extracranial measurable lesion;
• The laboratory test results within one week before enrollment meet the following conditions: 1) blood routine: HGB≥90g/L； WBC ≥ 4.0 × 109/L; Neut ≥ 2.0 × 109/l; PLT ≥ 100 × 109/l; 2) Blood biochemistry: TBIL ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN (ALT and AST ≤ 5 × ULN in patients with liver metastasis); Bun and Cr ≤ 1.5 × ULN and creatinine clearance rate ≥ 50 ml/min; 3) The results of echocardiography within two weeks before admission were consistent: left ventricular ejection fraction (LVEF)\>50%;
• The coagulation function was normal without active bleeding and thrombosis;
• Patients without contraindications to radiotherapy;
• The pregnancy test of patients of childbearing age was negative, and they voluntarily took effective and reliable contraceptive measures during the test;
• Subjects who have received anti-tumor treatment in the past should not be enrolled until the toxicity of previous treatment has stabilized and returned to the baseline level (except for the residual hair loss effect) or the CTCAE V5.0 score ≤ 1.

You may not qualify if:

• If the patient meets any of the following conditions, he cannot be selected:
• Patients with malignant tumors other than esophageal cancer, lung cancer and cervical cancer;
• Patients with other active malignant tumors in the first 5 years of randomization, such as squamous cell carcinoma of the skin, basal cell carcinoma of the skin, superficial bladder cancer, and breast cancer in situ, except those with locally curable tumors that have been cured;
• Patients who had participated in clinical trials of other drugs within 4 weeks before enrollment, and who had received radiotherapy for the target area within 4 weeks before entering this study, were vaccinated with live attenuated vaccine within 4 weeks before the first administration or during the study period;
• Arteriovenous thrombosis events occurred within 6 months, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism, etc;
• Receiving any other anti-tumor treatment at the same time;
• Those who are known to have a history of allergy to the drug components of this protocol have a history of telangiectatic ataxia or other radiation hypersensitivity;
• Subjects with active infectious diseases;
• Subjects with any severe and/or uncontrolled disease;
• Female patients during pregnancy and lactation, female patients with fertility and positive baseline pregnancy test;
• According to the judgment of the investigator, there are concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study (including but not limited to severe hypertension, severe pulmonary dysfunction/disease and severe diabetes that cannot be controlled by drugs);
• Having a clear history of neurological or mental disorders, including epilepsy or dementia, and unable to cooperate with the radiotherapy process;
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
• Diagnosed with immune deficiency or undergoing systemic glucocorticoid therapy or any other form of immunosuppressive therapy, and suffering from active or recurrent autoimmune diseases, except for vitiligo, alopecia, psoriasis or eczema that do not require systematic treatment; Hypothyroidism caused by autoimmune thyroiditis only needs a stable dose of hormone replacement therapy; Type I diabetes requiring only a stable dose of insulin replacement therapy;
• Have active or documented inflammatory bowel disease (such as Crohn's disease, ulcerative colitis), and active diverticulitis. The clinical manifestations of gastrointestinal obstruction, or the need for conventional parenteral fluid infusion, parenteral nutrition or indwelling gastric tube;

Sponsors & Collaborators

• Anhui Provincial Hospital: lead
• Akeso Pharmaceuticals, Inc.: collaborator

Study Sites (1)

The First Affiliated Hospital of University of Science and Technology of China

Hefei, British Columbia, 230001, China

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms; Esophageal Neoplasms; Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2024
• First Posted: January 30, 2024
• Study Start: September 1, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: July 9, 2025

Record last verified: 2025-07

Locations

CN (1)