Hypofractionated Versus Conventional Chemoradiotherapy Followed by Consolidative Immunotherapy in Locally Advanced NSCLC

NCT07052669 | Recruiting Phase 3

• 1 other identifier: GASTO-10134
• Study Type: interventional
• Target: 311
• Locations: 1 country
• Sites: 3

Brief Summary

Consolidative immunotherapy following concurrent chemoradiotherapy, based on the PACIFIC trial, has become the standard treatment for locally advanced non-small cell lung cancer (LANSCLC). Radiotherapy strategies for maximizing efficacy and local control require further investigation. This phase III, randomized controlled clinical trial is to investigate the efficacy and safety of hypofractionated chemoradiotherapy followed by consolidative immunotherapy versus conventional fractionated chemoradiotherapy followed by consolidative immunotherapy in LANSCLC patients.

Conditions

Locally Advanced Non-Small Cell Lung Cancer

Keywords

Hypofractionated radiotherapy; Conventionally fractionated radiotherapy; Concurrent Chemoradiotherapy; Consolidative immunotherapy

Outcome Measures

Primary Outcomes (1)

• Median Progression-Free Survival

  PFS measures the time from the start of treatment until the disease progresses or the patient dies from any cause, whichever occurs first.

  2 years

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  1-2 months after treatment

• Overall survival (OS)

  2 years

• Failure patterns

  2 years

• Safety: Adverse Events

  1 years after treatment

• Quality of life assessed by Quality of Life Core 30

  1 years after treatment

Study Arms (2)

Hypofractionated CCRT

EXPERIMENTAL

All patients will receive hypofractionated concurrent chemoradiotherapy, followed by consolidative immunotherapy for a maximum duration of 12 months.

Radiation: Hypofractionated Radiation Therapy; Drug: Concurrent Chemotherapy; Drug: Consolidative immunotherapy

Conventional fractionated CCRT

ACTIVE COMPARATOR

All patients will receive conventional fractionated concurrent chemoradiotherapy, followed by consolidative immunotherapy for a maximum duration of 12 months.

Radiation: Conventionally Fractionated Radiation Therapy; Drug: concurrent chemotherapy; Drug: Consolidative immunotherapy

Interventions

Hypofractionated Radiation Therapy RADIATION

All patients will receive split-course hypofractionated radiotherapy. First course of radiotherapy: Total dose of 4000 cGy in 10 daily fractions (400 cGy per fraction) or 3000 cGy in 6 daily fractions (500 cGy per fraction). Three weeks after the completion of the first course of hypofractionated radiotherapy, tumor response and toxicity will be evaluated. For patients who achieve a partial response and without grade 2 or higher respiratory toxicity, a second course of radiotherapy will be planned for the residue disease at a total dose of 2000 \~2400 cGy in 5\~6 fractions (400 cGy per fraction). The interval between the two courses of radiotherapy will be 28 days.

Hypofractionated CCRT

Conventionally Fractionated Radiation Therapy RADIATION

Patients in this group will receive a total dose of 6000- 6400 cGy in 30- 32 fractions, with 200 cGy per fraction.

Conventional fractionated CCRT

concurrent chemotherapy DRUG

Paclitaxel plus platinum-based chemotherapy.

Hypofractionated CCRT

Consolidative immunotherapy DRUG

Following the completion of chemoradiotherapy, PD-1/PD-L1 immune checkpoint inhibitor consolidation therapy will be administered for up to 12 months.

Conventional fractionated CCRT; Hypofractionated CCRT

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and Dated Informed Consent: Written informed consent must be provided prior to any study procedures, with the consent form signed and dated by the participant.
• Age Range: Male or female patients aged 18 to 75 years.
• Diagnosis: Patients must have locally advanced, unresectable (stage III) non-small cell lung cancer (NSCLC), with histological or cytological confirmation of the diagnosis.
• Previous Treatment: Treatment-naïve or previously treated with induction chemotherapy ± immunotherapy.
• Tumor Sample Requirement: Tumor tissue samples must be provided, and they should be sufficient for analysis. The samples must be unstained and archived.
• Driver gene testing: EGFR wild-type, ALK rearrangement-negative.
• Life Expectancy: Patients must have an expected survival of at least 12 weeks.
• Performance Status (PS): The patient's WHO Performance Status (PS) must be 0 or 1.
• Pregnancy Testing: Postmenopausal women, or women who have had a negative urine or serum pregnancy test within 14 days before the study medication (HCG sensitivity ≥ 25 IU/L or equivalent).
• Breastfeeding: Women must not be breastfeeding.
• Women of childbearing potential (WOCBP) must agree to use contraception during the study treatment period and for 5 months after the last dose of the investigational drug (i.e., 30 days \[ovulation cycle\] + approximately 5 half-lives of the study drug).
• Men who have sexual relations with WOCBP must agree to use contraception during the study treatment period and for 7 months after the last dose of the investigational drug (i.e., 90 days \[sperm renewal cycle\] + approximately 5 half-lives of the study drug).
• Males with no sperm production are exempt from contraception requirements. WOCBP who are not sexually active are exempt from contraception but must still undergo pregnancy testing as outlined above.
• Organ and Bone Marrow Function: The following laboratory parameters must be met:
• Forced expiratory volume in 1 second (FEV1) ≥ 800 mL Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L Platelets ≥ 100 × 10⁹/L Hemoglobin ≥ 9.0 g/dL Calculated creatinine clearance using the Cockcroft-Gault formula ≥ 50 mL/min Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) AST and ALT ≤ 2.5 × ULN

You may not qualify if:

• Patients meeting any of the following criteria should not be enrolled in the study:
• Concurrent participation in another clinical trial, except for observational (non-interventional) studies.
• Histological subtype of mixed small-cell and non-small-cell lung cancer. Use of immunosuppressive drugs within 28 days before treatment, except for intranasal or inhaled corticosteroids at physiological doses or systemic corticosteroids ≤10 mg/day of prednisone or equivalent.
• Major surgery within 4 weeks prior to enrollment (excluding procedures for vascular access).
• History or active autoimmune diseases within the past two years.
• Active or a history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of primary immunodeficiency.
• History of organ transplantation requiring immunosuppressive therapy.
• Average corrected QT interval (QTc) ≥470 ms calculated from three ECG cycles using the Bazett formula.
• Uncontrolled comorbidities, including but not limited to: Persistent or active infections. Symptomatic congestive heart failure. Poorly controlled hypertension. Unstable angina. Cardiac arrhythmias. Active peptic ulcer disease or gastritis. Active bleeding disorders. Hepatitis C or HIV infection. HBsAg-positive patients with HBV DNA \>500 IU/mL. Mental or social conditions that may limit adherence to study requirements or compromise the ability to provide informed consent.
• Known history of tuberculosis.
• Receipt of a live attenuated vaccine within 30 days before study initiation or planned during the study period.
• History of another primary malignancy within the past 5 years, except for adequately treated basal or squamous cell carcinoma of the skin or in situ cervical cancer.
• Pregnancy, breastfeeding, or not using effective contraception (for men and women of reproductive potential).
• Patients in the experimental group should not proceed to concurrent chemoradiotherapy if any of the following criteria are met:

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (3)

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

RECRUITING

Gansu Provincial Cancer Hospital

Lanzhou, Gansu, 730050, China

RECRUITING

Sun yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (11)

• Zhou R, Liu F, Zhang H, Wang D, Zhang P, Zheng S, Liu Y, Chen L, Guo J, Zou Y, Rong YM, Liu H, Qiu B. Fraction Dose Escalation of Hypofractionated Radiotherapy with Concurrent Chemotherapy and Subsequent Consolidation Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer: A Phase I Study. Clin Cancer Res. 2024 Jul 1;30(13):2719-2728. doi: 10.1158/1078-0432.CCR-23-3600.

  PMID: 38652815 BACKGROUND

• Filatenkov A, Baker J, Mueller AM, Kenkel J, Ahn GO, Dutt S, Zhang N, Kohrt H, Jensen K, Dejbakhsh-Jones S, Shizuru JA, Negrin RN, Engleman EG, Strober S. Ablative Tumor Radiation Can Change the Tumor Immune Cell Microenvironment to Induce Durable Complete Remissions. Clin Cancer Res. 2015 Aug 15;21(16):3727-39. doi: 10.1158/1078-0432.CCR-14-2824. Epub 2015 Apr 13.

  PMID: 25869387 BACKGROUND

• Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T, Weichselbaum RR, Fu YX. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009 Jul 16;114(3):589-95. doi: 10.1182/blood-2009-02-206870. Epub 2009 Apr 6.

  PMID: 19349616 BACKGROUND

• Tang C, Liao Z, Gomez D, Levy L, Zhuang Y, Gebremichael RA, Hong DS, Komaki R, Welsh JW. Lymphopenia association with gross tumor volume and lung V5 and its effects on non-small cell lung cancer patient outcomes. Int J Radiat Oncol Biol Phys. 2014 Aug 1;89(5):1084-1091. doi: 10.1016/j.ijrobp.2014.04.025. Epub 2014 Jul 8.

  PMID: 25035212 BACKGROUND

• Wild AT, Herman JM, Dholakia AS, Moningi S, Lu Y, Rosati LM, Hacker-Prietz A, Assadi RK, Saeed AM, Pawlik TM, Jaffee EM, Laheru DA, Tran PT, Weiss MJ, Wolfgang CL, Ford E, Grossman SA, Ye X, Ellsworth SG. Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients With Unresectable Pancreatic Cancer. Int J Radiat Oncol Biol Phys. 2016 Mar 1;94(3):571-9. doi: 10.1016/j.ijrobp.2015.11.026. Epub 2015 Dec 1.

  PMID: 26867885 BACKGROUND

• Zhou R, Qiu B, Xiong M, Liu Y, Peng K, Luo Y, Wang D, Liu F, Chen N, Guo J, Zhang J, Huang X, Rong Y, Liu H. Hypofractionated Radiotherapy followed by Hypofractionated Boost with weekly concurrent chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Results of A Prospective Phase II Study (GASTO-1049). Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2):387-399. doi: 10.1016/j.ijrobp.2023.04.021. Epub 2023 Apr 25.

  PMID: 37100160 BACKGROUND

• Kong FM, Ten Haken RK, Schipper M, Frey KA, Hayman J, Gross M, Ramnath N, Hassan KA, Matuszak M, Ritter T, Bi N, Wang W, Orringer M, Cease KB, Lawrence TS, Kalemkerian GP. Effect of Midtreatment PET/CT-Adapted Radiation Therapy With Concurrent Chemotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer: A Phase 2 Clinical Trial. JAMA Oncol. 2017 Oct 1;3(10):1358-1365. doi: 10.1001/jamaoncol.2017.0982.

  PMID: 28570742 BACKGROUND

• Durm GA, Jabbour SK, Althouse SK, Liu Z, Sadiq AA, Zon RT, Jalal SI, Kloecker GH, Williamson MJ, Reckamp KL, Langdon RM, Kio EA, Gentzler RD, Adesunloye BA, Harb WA, Walling RV, Titzer ML, Hanna NH. A phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non-small cell lung cancer: Hoosier Cancer Research Network LUN 14-179. Cancer. 2020 Oct 1;126(19):4353-4361. doi: 10.1002/cncr.33083. Epub 2020 Jul 22.

  PMID: 32697352 BACKGROUND

• Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Ozguroglu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. doi: 10.1200/JCO.21.01308. Epub 2022 Feb 2.

  PMID: 35108059 BACKGROUND

• Gray JE, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, Cho BC, Planchard D, Paz-Ares L, Faivre-Finn C, Vansteenkiste JF, Spigel DR, Wadsworth C, Taboada M, Dennis PA, Ozguroglu M, Antonia SJ. Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC-Update from PACIFIC. J Thorac Oncol. 2020 Feb;15(2):288-293. doi: 10.1016/j.jtho.2019.10.002. Epub 2019 Oct 14.

  PMID: 31622733 BACKGROUND

• Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8.

  PMID: 28885881 BACKGROUND

Study Officials

• Hui Liu, Professor

  Sun yat-sen universtiy cancer center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bo Qiu, Professor

CONTACT

02087343031; qiubo@sysucc.org.cn

Hui Liu, Professor

CONTACT

02087343031; liuhui@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 30, 2025
• First Posted: July 6, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: July 23, 2025

Record last verified: 2025-07

Locations

CN (3)