Locally Advanced Lung Carcinoma
Conditions
Keywords
Locally advanced non-small cell lung cancer, Definitive hypofractionated chemoradiotherapy, Fraction dose escalation, Consolidation immunotherapy
Brief summary
This Phase 1 trial aimed to determine the maximum tolerated fraction dose (MTD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer (LA-NSCLC).
Interventions
RADIATIONHypofractionated radiotherapy
Split-course adaptive HRT-CHT is administered at the following three dose levels: 1. Level 1: DT 4500cGy/15 daily fractions/300cGy in the first course，DT 1500cGy/5 daily fractions/300cGy in the second course; 2. Level 2: DT 4000cGy/10 daily fractions/400cGy in the first course， DT 2000cGy/5 daily fractions/400cGy in the second course; 3. Level 3: DT 3000cGy/6 daily fractions/500cGy in the first course， DT 3000cGy/6 daily fractions/500cGy in the second course.
DRUGConcurrent chemotherapy
weekly infusion of docetaxel (25mg/m2) and cisplatin (25mg/m2) during RT
Consolidative immunotherapy (PD-1 or PD-L1 inhibitor) up to 1 year is administered for those without disease progression after HRT-CHT.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Non-small cell lung cancer confirmed by histology. * Tumor size is measured according to RECIST standard. * Unresectable stage IIIA (N2) and IIIB/IIIC, confirmed by PET-CT/or chest and abdomen CT, brain MRI, and whole body bone scan. * 18-75 years old, regardless of gender. * The ECOG score is 0-1. * Newly treated or underwent neoadjuvant chemotherapy and/or immunotherapy. * Have not received chest radiotherapy in the past. * Serum hemoglobin ≥10 mg/dL, platelets ≥100000/μL, absolute neutrophil count ≥1500/μL. * Serum creatinine ≤1.25 times UNL or creatinine clearance ≥60 ml/min. * Serum bilirubin ≤1.5 times UNL, AST (SGOT) and ALT (SGPT) ≤2.5 times UNL, alkaline phosphatase≤ 5 times UNL. * FEV1\>1 L. * CB6 normal range. * The patient and his family members agree and sign an informed consent form.
Exclusion criteria
* Other malignant tumors in the past or during treatment, except for non-melanoma of the skin or carcinoma in situ of the cervix. * Any other diseases or conditions are contraindications to chemotherapy (such as active infection, within 6 months after myocardial infarction, symptomatic heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmia, immunosuppressive therapy). * Pregnant or breastfeeding women, women who have not undergone a pregnancy test (within 14 days before the first dose), and pregnant women. * Those who are pregnant, breastfeeding or have fertility but have not taken contraceptive measures. * People with bleeding tendency. * Those who participated in other clinical trials within 30 days before participating in this experiment. * Drug addiction, long-term alcoholism, and AIDS patients. * People with uncontrollable seizures or loss of self-control due to mental illness. * People with a history of severe allergies or specific physique. * The researcher believes that the patient is inappropriate to participate in this trial. Exit criteria * The treatment cannot be carried out in accordance with the requirements of the research protocol; * The patient has an allergic reaction ≥ grade 4 or a serious adverse reaction to the study drug; * The patient is pregnant or has not used adequate contraceptive measures; * The researcher judges that the patient should not continue to participate the clinical trial; * The subject asked to withdraw.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the maximally tolerated fraction dose | 1 year | The maximum tolerated fraction dose was defined as the highest DL in which \<=2 patients of the 6 treated patients experienced G3+ toxicity and \<=1 patient experienced G4+ toxicity within 12 months after RT. If a patient had multiple types of toxicities, only the highest grade of toxicity was counted. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | 2 months after radiotherapy | Proportion of patients with PR and CR at 2 months after radiotherapy |
| Overall survival | 1-year | — |
| Progression-free survival | 1-year | — |
| Distant-metastasis free survival | 1-year | — |
| Loco-regional recurrence-free survival | 1-year | — |
Countries
China
Outcome results
None listed