Chemotherapy-immunotherapy-based Split-course Adaptive Hypofractionated Radiotherapy for Extensive-stage SCLC

NCT06816966 | Enrolling By Invitation Phase 2

• 1 other identifier: 2023YF056-02
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, single-arm, phase Ⅱ trial evaluating the safety and efficacy of Chemotherapy-immunotherapy-based split-course adaptive hypofractionated radiotherapy for extensive-stage SCLC

Conditions

Small-cell Lung Cancer

Keywords

Radiation; split; hypofractionated radiotherapy

Outcome Measures

Primary Outcomes (2)

• 6-month Progression-Free Survival rate

  6-month Progression-Free Survival rate from consent.

  Time from consent to any documented progression or death due to any cause, whichever occurs first, assessed up to 6 months.

• Safety

  For each patient, the maximum severity reported for both immune mediated and non-immune mediated adverse events will be used in the summaries. Adverse events will be summarized regardless of relationship to protocol treatment as assessed by the investigator. All adverse events, adverse events leading to withdrawal, interruption or modification of protocol treatment, grade \>= 3 adverse events, and serious adverse events will be summarized. Deaths and cause of death will be summarized. The rate of treatment-related adverse events using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version \[v.\]5.0) will be reported with the frequency and severity (e.g., type, grade, and attribution). All adverse events will be classified by the relationship to treatment.

  Up to 6 months

Secondary Outcomes (2)

• Overall survival

  Up to 2 years

• Failure pattern

  Up to 2 years

Study Arms (1)

Chemotherapy-immunotherapy-based split-course adaptive hypofractionated radiotherapy

EXPERIMENTAL

Each cycle of chemotherapy and immunotherapy is synchronized with a 5 Gy dose of radiotherapy, which is precisely targeted at the gross tumor located within the thoracic cavity. The delineation of the target is adaptively adjusted based on the volumetric reduction of the tumor observed at each treatment session.

Radiation: split-course adaptive hypofractionated radiotherapy

Interventions

split-course adaptive hypofractionated radiotherapy RADIATION

Each treatment cycle comprises a solitary radiotherapy session, which allows for its integration with chemotherapy and immunotherapy. The radiotherapy sessions are scheduled at three-week intervals, thereby affording extended recovery periods for normal tissues. An adaptive radiotherapy plan is implemented for each cycle, enabling precise adjustments to the treatment target area in response to the reduction in tumor volume.

Chemotherapy-immunotherapy-based split-course adaptive hypofractionated radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any pathologic confirmation of ES-SCLC at any site, either primary or metastases.
• Patients must have measurable disease and 3 or fewer observable liver metastases.
• If there is a pleural effusion, patients will be eligible if thoracentesis is cytologically negative or if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging
• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate normal organ and bone marrow function
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
• Life expectancy greater than six (6) months
• If the autoimmune disease is not active for over 3 years and the patient is not receiving immunosuppressive treatment such as methotrexate or steroids above a dose equivalent to 10 mg prednisone daily, the patient is eligible.
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
• Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible.
• Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations are excluded only if they have active disease with acute exacerbation and on immunosuppressive medications within the 12 months prior to enrollment. They are eligible otherwise.
• Severe, active co-morbidity defined as follows: Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of radiation, chemotherapy and ICIs or that may affect the interpretation of the results or render the patient at high risk from treatment complications;
• Active tuberculosis;
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.

You may not qualify if:

• Metastatic disease invading the liver (\> 3 metastases)
• Patients with malignant pleural and/or pericardial effusions
• Prior radiotherapy in the thorax that would result in overlapping RT fields
• Active autoimmune disease, including, but not limited to: systemic lupus erythematosus; rheumatoid arthritis; inflammatory bowel disease (e.g. Crohn's, ulcerative colitis); vascular thrombosis associated with antiphospholipid syndrome; Wegener's granulomatosis; Sjogren's syndrome; Guillain-Barre syndrome; multiple sclerosis; vasculitis; or glomerulonephritis.
• Known immunosuppressive disease, for example history of bone marrow transplant or chronic lymphocytic leukemia (CLL);
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months;
• History of recent myocardial infarction within 6 months prior to registration.
• Clinically significant interstitial lung disease;
• History of allogeneic organ transplant;
• Patients positive for human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months and a stable regimen of highly active anti-retroviral (HAART) HIV-positive patients must have no requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections.

Sponsors & Collaborators

• Fujian Medical University Union Hospital: lead

Study Sites (1)

Fujian Medical University Union Hospital,

Fuzhou, Fujian, 350000, China

Location

Related Publications (5)

• Jeremic B, Shibamoto Y, Nikolic N, Milicic B, Milisavljevic S, Dagovic A, Aleksandrovic J, Radosavljevic-Asic G. Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer: A randomized study. J Clin Oncol. 1999 Jul;17(7):2092-9. doi: 10.1200/JCO.1999.17.7.2092.

  PMID: 10561263 BACKGROUND

• Slotman BJ, van Tinteren H, Praag JO, Knegjens JL, El Sharouni SY, Hatton M, Keijser A, Faivre-Finn C, Senan S. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet. 2015 Jan 3;385(9962):36-42. doi: 10.1016/S0140-6736(14)61085-0. Epub 2014 Sep 14.

  PMID: 25230595 BACKGROUND

• Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. doi: 10.1056/NEJMoa1809064. Epub 2018 Sep 25.

  PMID: 30280641 BACKGROUND

• Bernabe-Caro R, Chen Y, Dowlati A, Eason P. Current and Emerging Treatment Options for Patients With Relapsed Small-cell Lung Carcinoma: A Systematic Literature Review. Clin Lung Cancer. 2023 May;24(3):185-208. doi: 10.1016/j.cllc.2023.01.012. Epub 2023 Feb 8.

  PMID: 36907793 BACKGROUND

• Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers. 2021 Jan 14;7(1):3. doi: 10.1038/s41572-020-00235-0.

  PMID: 33446664 BACKGROUND

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cheng Chen

Study Record Dates

• First Submitted: January 16, 2025
• First Posted: February 10, 2025
• Study Start: December 26, 2023
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2028
• Last Updated: February 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: To be made public in the form of a published article about 1 year after the trial is completed
• Access Criteria: Researchers who have approval from an Institutional Review Board (IRB).

Locations

CN (1)