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

NCT ID: NCT07052669

Last Updated: 2025-07-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

311 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-01

Study Completion Date

2029-06-30

Brief Summary

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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.

Detailed Description

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This phase III, randomized controlled trial aims to investigate the efficacy and safety of hypofractionated chemoradiotherapy followed by consolidative immunotherapy versus conventional fractionated chemoradiotherapy followed by consolidative immunotherapy in LANSCLC patients. Patients will be randomized in a 2:1 ratio to the following two groups: (1) Study group: Patients in this group will undergo hypofractionated chemoradiotherapy, followed by consolidative immunotherapy for a maximum duration of 12 months. (2) Control group: Patients in this group will receive conventional fractionated chemoradiotherapy followed by consolidative immunotherapy for a maximum duration of 12 months.

Conditions

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Locally Advanced Non-Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Hypofractionated CCRT

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

Group Type EXPERIMENTAL

Hypofractionated Radiation Therapy

Intervention Type 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.

Concurrent Chemotherapy

Intervention Type DRUG

Paclitaxel plus platinum-based chemotherapy.

Consolidative immunotherapy

Intervention Type 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

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

Group Type ACTIVE_COMPARATOR

Conventionally Fractionated Radiation Therapy

Intervention Type RADIATION

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

concurrent chemotherapy

Intervention Type DRUG

Paclitaxel plus platinum-based chemotherapy or pemetrexed plus platinum-based chemotherapy.

Consolidative immunotherapy

Intervention Type DRUG

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

Interventions

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Hypofractionated Radiation Therapy

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.

Intervention Type RADIATION

Conventionally Fractionated Radiation Therapy

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

Intervention Type RADIATION

Concurrent Chemotherapy

Paclitaxel plus platinum-based chemotherapy.

Intervention Type DRUG

concurrent chemotherapy

Paclitaxel plus platinum-based chemotherapy or pemetrexed plus platinum-based chemotherapy.

Intervention Type DRUG

Consolidative immunotherapy

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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:

* Presence of distant metastases.
* Locoregional progression making definitive concurrent chemoradiotherapy unfeasible due to normal tissue dose constraints (assessed by the radiation oncologist).
* WHO performance status score of 2-4.
* Impaired organ or bone marrow function, including:

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. Creatinine clearance (Cockcroft-Gault formula) \<50 mL/min. Serum bilirubin \>1.5 × upper limit of normal (ULN). AST and ALT \>2.5 × ULN.

\- Patient withdrawal from the study.

Patients should not proceed to consolidation immunotherapy if any of the following criteria are met:

* Disease progression during concurrent chemoradiotherapy.
* Use of immunosuppressive drugs within 28 days before the first dose of tislelizumab, except for physiological doses of intranasal or inhaled corticosteroids or systemic corticosteroids ≤10 mg/day of prednisone or equivalent. Use of corticosteroids to manage chemoradiotherapy-related toxicity is permitted.
* Persistent unresolved CTCAE grade \>2 toxicities from prior chemoradiotherapy.
* Grade ≥2 pneumonitis resulting from prior chemoradiotherapy.
* Any prior grade ≥3 immune-related adverse event (irAE) or unresolved irAE \> grade 1.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sun Yat-sen University

OTHER

Sponsor Role lead

Responsible Party

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Hui Liu

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hui Liu, Professor

Role: PRINCIPAL_INVESTIGATOR

Sun yat-sen universtiy cancer center

Locations

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The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

Site Status RECRUITING

Gansu Provincial Cancer Hospital

Lanzhou, Gansu, China

Site Status RECRUITING

Sun yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Bo Qiu, Professor

Role: CONTACT

02087343031

Hui Liu, Professor

Role: CONTACT

02087343031

Facility Contacts

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Tao Zhang, MD

Role: primary

Shihong Wei, M.Med

Role: primary

Hui Liu, MD

Role: primary

02087343031

References

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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Reference Type BACKGROUND
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Other Identifiers

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GASTO-10134

Identifier Type: -

Identifier Source: org_study_id

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