Radiotherapy to All Residual Lesions After Chemoimmunotherapy

Chemoimmunotherapy Followed by All-residual-lesions Radiotherapy for Extensive-stage Small-cell Lung Cancer: A Phase I/II Trial

Extensive-stage small-cell lung cancer is a lethal malignancy with an extremely poor prognosis. First-line chemotherapy could only achieve an overall survival of approximately 10 months. CREST study demonstrated that the addition of thoracic radiotherapy to the patients who responded to chemotherapy could increase the 2-year survival rate from 3% to 13%. CASPIAN and IMpower 133 trials have established the standard modality of first-line chemoimmunotherapy for extensive-stage small-cell lung cancer and prolonged the overall survival to 13 months. Both the addition of thoracic radiotherapy and immunotherapy to chemotherapy were able to improve the survival. Recently, several retrospective studies have demonstrated the effectiveness and safety of the combination of thoracic radiotherapy and chemoimmunotherapy. In a prospective study, 4-6 cycles of first-line chemotherapy with Adebrelimab followed by thoracic radiotherapy achieved the progression-free survival of 10.1 months and overall survival of 21.4 months, which was longer than chemoimmunotherapy. Another study demonstrated not only thoracic radiotherapy, but also radiotherapy to metastatic lesions could ameliorate survival. Therefore, we supposed that whether radiotherapy to all residual lesions after first-line chemoimmunotherapy could further improve survival for patients with extensive-stage small-cell lung cancer.

Study Overview

• Status: Recruiting
• Conditions: Extensive-stage Small Cell Lung Cancer
• Intervention / Treatment: Radiation: Radiotherapy to all residual lesions; Drug: Chemoimmunotherapy

Detailed Description

Trial design: To enroll 150 patients diagnosed with extensive-stage small-cell lung cancer to receive first-line chemoimmunotherapy with or without radiotherapy to all residual lesions.

Primary endpoint: Progression-free Survival Secondary endpoint: Overall Survival, Objective Response Rate, Duration of Response, Disease Control Rate.

Randomization: All the enrolled patients would be randomly assigned to chemoimmunotherapy group and chemoimmunotherapy with radiotherapy group using random table method.

All enrolled patients with accordance to the inclusion criteria would first receive 4 to 6 cycles of chemoimmunotherapy (etoposide and cisplatin & carboplatin with Adebrelimab). Then patients who were evaluated as partial response or stable disease would be assigned randomly to receive radiotherapy to all residual lesions followed by Adebrelimab maintenance or only Adebrelimab maintenance up to 2 years.

Chemoimmunotherapy: Etoposide 80-100mg/m2 day 1, 2, 3 and cisplatin 75-80mg/m2 day 1 & carboplatin AUC 5 day 1 and Adebrelimab 1200mg day 1 q3w totally 4 to 6 cycles.

Immunotherapy maintenance: Adebrelimab 1200mg q3w to 2 year or disease progression & untolerated toxicity.

Response evaluation: After 4 to 6 cycles of chemoimmunotherapy, patients would undertake response evaluation according to RECIST criteria. These patients who were evaluated as partial response and stable disease could be included into the study and receive randomization.

Radiotherapy to residual lesions: Patients assigned to chemoimmunotherapy with radiotherapy group would first receive PET-CT and cranial contrasted MRI to ascertain residual lesions. All residual lesions would be irradiated in a hypofractionated manner. Radiotherapy should be completed in two weeks. The suggested dose fraction for different lesion was as follows:

Thoracic lesion: 40Gy/10f Cranial lesion: Hippocamps-sparing whole brain irradiation of 30Gy/10f with or without simultaneous integrated lesion boost of 40Gy/10f Hepatic or adrenal lesion: 40Gy/10f Osseous lesion: 30Gy/10f or 40Gy/10f Dose constraint to organs at risk could be referred to QUANTEC criteria (30Gy/10f) and Timmerman's sheet (40Gy/10f) Follow-up: Patients should be follow-up every three months right after the completion of the final cycle of immunotherapy to 3 years after that. Then follow-up every half year is allowed to 5 years. After 5 years, follow-up every year is appropriate. In follow-up, chest CT and abdominal ultrasonography should be implemented. Cranial MRI should be performed every half year. Bone scan should be undertaken every year for all patients.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Dong Qian, M.D.; Phone Number: +8619156007756; Email: qiandong@ustc.edu.cn
• Study Contact Backup: Name: Xiao-yang Li, M.D.; Phone Number: +8618701851829; Email: drxyl@ustc.edu.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230011
      • Recruiting
      • Anhui Provincial Hospital
      • Contact: Dong Qian, M.D.; Phone Number: 800-666-7777; Email: bingyan29618@ustc.edu.cn
      • Principal Investigator: Dong Qian, M.D

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18-70 years old;
• ECOG 0-1;
• Adequate organ function to tolerate chemotherapy, immunotherapy and radiotherapy;
• Small-cell lung cancer;
• Extensive stage confirmed by cranial MRI, chest CT, abdominal ultrasonograph, bone scan or cranial MRI and PET-CT;
• Signature of inform consent.

Exclusion Criteria:

Younger than 18 years old or older than 70 years old;

• ECOG>1;
• Inadequate organ function to tolerate chemotherapy, immunotherapy and radiotherapy;
• Non-small cell lung cancer and other neuroendocrine carcinoma including typical or atypical carcinoid, large-cell neuroendocrine carcinoma;
• Limited stage confirmed by cranial MRI, chest CT, abdominal ultrasonograph, bone scan or cranial MRI and PET-CT;
• No signature of inform consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Chemoimmunotherapy group; Patients assigned to chemoimmunotherapy group would receive 4 to 6 cycles of standard chemoimmunotherapy followed by immunotherapy maintenance to 2 years.	Drug: Chemoimmunotherapy; atients assigned to chemoimmunotherapy group would receive 4 to 6 cycles of chemoimmunotherapy followed by consolidative immunotherapy
Experimental: Chemoimmunotherapy with radiotherapy group; Patients assigned to chemoimmunotherapy group would receive 4 to 6 cycles of standard chemoimmunotherapy followed by radiotherapy to all residual lesions and immunotherapy maintenance to 2 years.	Radiation: Radiotherapy to all residual lesions; Patients assigned to chemoimmunotherapy with radiotherapy group would first receive PET-CT and cranial contrasted MRI to ascertain residual lesions. All residual lesions would be irradiated in a hypofractionated manner.; Drug: Chemoimmunotherapy; atients assigned to chemoimmunotherapy group would receive 4 to 6 cycles of chemoimmunotherapy followed by consolidative immunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	The survival time from diagnose of the disease to progression of the disease	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The survival time from diagnose of the disease to death	3 years

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Investigators: Principal Investigator: Dong Qian, M.D, Anhui Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: June 24, 2024
• First Submitted That Met QC Criteria: June 24, 2024
• First Posted (Actual): June 28, 2024

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: radiotherapy; small-cell lung cancer; extensive-stage; residual lesion
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: 2024-ky236

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