Hypofractionated Radiotherapy Combined With PD-1 Inhibitor Sequential GM-CSF and IL-2 for the Treatment of Advanced Refractory Solid Tumors (PRaG2.0)

A Prospective Multicenter Clinical Study of Hypofractionated Radiotherapy Combined With PD-1 Inhibitor Sequential GM-CSF and IL-2 for the Treatment of Advanced Refractory Solid Tumors

This is a prospective multicenter clinical study to determine the efficacy and safety of hypofractionated radiotherapy combined with PD-1 inhibitor sequential GM-CSF and IL-2 for advanced multiple metastatic solid tumors

Study Overview

• Status: Recruiting
• Conditions: Advanced Refractory Solid Tumors
• Intervention / Treatment: Radiation: Hypofractionated radiotherapy; Drug: PD-1 inhibitor; Drug: GM-CSF; Drug: IL-2

• Study Type: Interventional
• Enrollment (Anticipated): 66
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liyuan Zhang, Dr; Phone Number: 0086-0512-67784827; Email: zhangliyuan126@126.com

Study Locations

• China
  • Beijing, China
    • Not yet recruiting
    • Peking University Third Hospital
    • Contact: Hao Wang, Dr
  • Changsha, China
    • Not yet recruiting
    • Hunan Cancer Hospital
    • Contact: Pei Yang, Dr
  • Changsha, China
    • Not yet recruiting
    • The Second Xiangya Hospital of Central South University
    • Contact: Pin Liu, Dr
  • Changsha, China
    • Not yet recruiting
    • Xiangya Hospital of Central South University
    • Contact: Haijun Wu, Dr
  • Chongqing, China
    • Not yet recruiting
    • Chongqing University Cancer Hospital
    • Contact: Wei Zhou, Dr
  • Guangzhou, China
    • Not yet recruiting
    • The Sixth Affiliated Hospital ，Sun Yat-seen University
    • Contact: Xiangbo Wan, Dr
  • Hangzhou, China
    • Recruiting
    • Cancer Hospital of The University of Chinese Academy of Sciences
    • Contact: Wei Feng, Dr
  • Hefei, China
    • Recruiting
    • The First Affiliated Hospital of Ustc
    • Contact: Dong Qian, Dr
  • Jinan, China
    • Not yet recruiting
    • Shandong Provincial Tumor Hospital
    • Contact: Dali Han, Dr
  • Nanchang, China
    • Not yet recruiting
    • The Second Affiliated Hospital of Nanchang University
    • Contact: Hua Wang, Dr
  • Nanjing, China
    • Not yet recruiting
    • Jiangsu Cancer Hospital
    • Contact: Li Yin, Dr
  • Shanghai, China
    • Not yet recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Guichao Li, Dr
  • Suzhou, China
    • Recruiting
    • Second Affiliated Hospital of Soochow University
    • Contact: Liyuan Zhang, Dr; Phone Number: 0086-0512-67784827; Email: zhangliyuan126@126.com
  • Wuhan, China
    • Not yet recruiting
    • Renmin Hospital of Wuhan University
    • Contact: Xiangpan Li, Dr
  • Wuxi, China
    • Recruiting
    • Jiangyin People's Hospital
    • Contact: Jiang Wang, Dr
  • Xuzhou, China
    • Recruiting
    • The Affilated Hospital of Xuzhou Medical University
    • Contact: Jiangshe Wang, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. The enrolled patients meet the recurrence or metastasis of advanced solid malignant tumors, have a clear pathological diagnosis report or medical history, the guidelines do not clearly recommend standard treatment plans or cannot tolerate standard treatment plans, and have clear measurable metastatic lesions (>1cm);
3. No congestive heart failure, unstable angina, or unstable arrhythmia occurred in the past 6 months.
4. The patient's activity status score is 0-3 points based on the Eastern Cooperative Oncology Group (ECOG) scoring method, and the life expectancy assessment is ≥3 months.
5. No serious hematopoietic function, abnormal heart, lung, liver, kidney function and immune deficiency in the past.
6. One week before admission, the absolute value of T lymphocytes was ≥0.5 times the lower limit of normal, and neutrophils ≥1.0×109/L; AST and ALT were ≤3.0 times the upper limit of normal (for liver cancer/liver metastasis ≤5.0 times) Upper limit of normal); creatinine ≤3.0 times the upper limit of normal.
7. The patient have the ability to understand and voluntarily sign an informed consent form.

Exclusion Criteria:

1. Pregnant or breastfeeding women.
2. Those with a history of other malignant diseases in the last 5 years, except for cured skin cancer and cervical carcinoma in situ.
3. If there is a history of uncontrolled epilepsy, central nervous system disease or mental disorder, the investigator's judgment of its clinical severity may hinder the signing of informed consent or affect the patient's compliance with medication.
4. Clinically serious (ie active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) grade II or more severe congestive heart failure, or severe arrhythmia requiring drug intervention, or recent A history of myocardial infarction within 12 months.
5. Those who need immunosuppressive therapy for organ transplantation.
6. A known major active infection, or the researcher's judgment has major blood, kidney, metabolism, gastrointestinal, endocrine function or metabolic disorders, or other serious uncontrolled accompanying diseases.
7. Those who are allergic to any research drug ingredients.
8. A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation, or those with other immune-related diseases that require long-term oral hormone therapy.
9. In the period of acute and chronic tuberculosis infection (T-spot test is positive, patients with suspected tuberculosis foci on chest X-ray).
10. Other situations that the researcher thinks are not suitable for inclusion in the group.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: RT+PD-1+GM-CSF+IL-2	Radiation: Hypofractionated radiotherapy; 10-24Gy/5-8Gy/2-3f; Drug: PD-1 inhibitor; q3w, until PD; Drug: GM-CSF; 200μg, D1-D7, ≥8 cycles; Drug: IL-2; at a dose of 2 million IU, D8-D14, ≥8 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression free survival，PFS	Time from cycle 1, day 1 of treatment to disease progression or death due to any cause	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate，ORR	The proportion of patients with at least one tumor scan of complete response (CR) or partial response (PR) using RECIST v1.1.	Up to 3 years
Disease control rate，DCR	The proportion of patients with at least one tumor scan of complete response (CR) or partial response (PR) or stable disease (SD) using RECIST v1.1.	Up to 3 years
Overall survival，OS	Time from cycle 1, day 1 of treatment until death due to any cause	Up to 3 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Liyuan Zhang, Dr, Second Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 30, 2021
• Primary Completion (ANTICIPATED): August 1, 2023
• Study Completion (ANTICIPATED): August 1, 2024

Study Registration Dates

• First Submitted: April 19, 2021
• First Submitted That Met QC Criteria: May 16, 2021
• First Posted (ACTUAL): May 19, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 9, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: IL-2; PD-1 inhibitor; hypofractionated radiotherapy; GM-CSF
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immune Checkpoint Inhibitors
• Other Study ID Numbers: JD-LK-2021-035-01

Drug and device information, study documents

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