Fraction Dose Escalation of Hypo-fractionated Radiotherapy in LANSCLC

Sun Yat-sen University

Status and phase: Completed; Phase 1

Conditions: Locally Advanced Lung Carcinoma

Treatments: Drug: Concurrent chemotherapy; Drug: Consolidation immunotherapy; Radiation: Hypofractionated radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT04951063

GASTO-1080

Details and patient eligibility

About

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).

Enrollment: 18 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Split-course adaptive HRT-CHT

Experimental group

Description:

In keeping the same total radiation dose (60Gy), we escalate the fraction dose to find the maximum tolerable fraction dose. 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. RT is delivered using the IMRT technique with daily cone-beam CT image guidance. The dose limitation of organ at risk (OAR) are shown in Table 1. Patients receive a 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.

Treatment:

Drug: Concurrent chemotherapy

Drug: Consolidation immunotherapy

Radiation: Hypofractionated radiotherapy