Fraction Dose Escalation of Hypo-fractionated Radiotherapy in LANSCLC

NCT04951063 | Completed Phase 1

• 1 other identifier: GASTO-1080
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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).

Conditions

Locally Advanced Lung Carcinoma

Keywords

Locally advanced non-small cell lung cancer; Definitive hypofractionated chemoradiotherapy; Fraction dose escalation; Consolidation immunotherapy

Outcome Measures

Primary Outcomes (1)

• the maximally tolerated fraction dose

  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.

  1 year

Secondary Outcomes (5)

• Objective response rate

  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

Study Arms (1)

Split-course adaptive HRT-CHT

EXPERIMENTAL

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.

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

Interventions

Hypofractionated radiotherapy RADIATION

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.

Split-course adaptive HRT-CHT

Concurrent chemotherapy DRUG

weekly infusion of docetaxel (25mg/m2) and cisplatin (25mg/m2) during RT

Split-course adaptive HRT-CHT

Consolidation immunotherapy DRUG

Consolidative immunotherapy (PD-1 or PD-L1 inhibitor) up to 1 year is administered for those without disease progression after HRT-CHT.

Split-course adaptive HRT-CHT

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun yat-sen University Cancer Center

Guangzhou, Guangdong, 510000, China

Location

Related Publications (15)

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MeSH Terms

Interventions

Radiation Dose Hypofractionation

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics

Study Officials

• Hui Liu, Professor

  Sun yat-sen universtiy cancer center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 26, 2021
• First Posted: July 6, 2021
• Study Start: June 1, 2021
• Primary Completion: March 31, 2023
• Study Completion: September 30, 2023
• Last Updated: December 15, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)