Radiotherapy to All Residual Lesions After Chemoimmunotherapy

NCT ID: NCT06479473

Last Updated: 2024-08-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-01
• Study Completion Date: 2026-03-31

Brief Summary

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.

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.

Conditions

Extensive-stage Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemoimmunotherapy group

Patients assigned to chemoimmunotherapy group would receive 4 to 6 cycles of standard chemoimmunotherapy followed by immunotherapy maintenance to 2 years.

Group Type: ACTIVE_COMPARATOR

Chemoimmunotherapy

Intervention Type: DRUG

atients assigned to chemoimmunotherapy group would receive 4 to 6 cycles of chemoimmunotherapy followed by consolidative immunotherapy

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.

Group Type: EXPERIMENTAL

Radiotherapy to all residual lesions

Intervention Type: RADIATION

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.

Chemoimmunotherapy

Intervention Type: DRUG

atients assigned to chemoimmunotherapy group would receive 4 to 6 cycles of chemoimmunotherapy followed by consolidative immunotherapy

Interventions

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.

Intervention Type: RADIATION

Chemoimmunotherapy

atients assigned to chemoimmunotherapy group would receive 4 to 6 cycles of chemoimmunotherapy followed by consolidative immunotherapy

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Anhui Provincial Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Dong Qian

M.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dong Qian, M.D

Role: PRINCIPAL_INVESTIGATOR

Anhui Provincial Hospital

Locations

Anhui Provincial Hospital

Hefei, Anhui, China

Site Status: RECRUITING

Countries

China

Central Contacts

Dong Qian, M.D.

Role: CONTACT

qiandong@ustc.edu.cn

+8619156007756

Xiao-yang Li, M.D.

Role: CONTACT

drxyl@ustc.edu.cn

+8618701851829

Facility Contacts

Dong Qian, M.D.

Role: primary

bingyan29618@ustc.edu.cn

800-666-7777

Other Identifiers

2024-ky236

Identifier Type: -

Identifier Source: org_study_id