Fraction Dose Escalation of Hypo-fractionated Radiotherapy in LANSCLC

December 10, 2023 updated by: Hui Liu, Sun Yat-sen University

Fraction Dose Escalation of Hypofractionated Radiotherapy With Concurrent Chemotherapy and Subsequent Consolidation Immunotherapy in Locally Advanced Non-small Cell Lung Cancer: a Phase 1 Study

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510000
        • Sun yat-sen University Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Split-course adaptive HRT-CHT

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

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.
Drug: Consolidation immunotherapy
Consolidative immunotherapy (PD-1 or PD-L1 inhibitor) up to 1 year is administered for those without disease progression after HRT-CHT.
Drug: Concurrent chemotherapy
weekly infusion of docetaxel (25mg/m2) and cisplatin (25mg/m2) during RT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the maximally tolerated fraction dose
Time Frame: 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.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 1-year
1-year
Objective response rate
Time Frame: 2 months after radiotherapy
Proportion of patients with PR and CR at 2 months after radiotherapy
2 months after radiotherapy
Progression-free survival
Time Frame: 1-year
1-year
Distant-metastasis free survival
Time Frame: 1-year
1-year
Loco-regional recurrence-free survival
Time Frame: 1-year
1-year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Hui Liu, Professor, Sun yat-sen universtiy cancer center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2021

Primary Completion (Actual)

March 31, 2023

Study Completion (Actual)

September 30, 2023

Study Registration Dates

First Submitted

June 26, 2021

First Submitted That Met QC Criteria

June 26, 2021

First Posted (Actual)

July 6, 2021

Study Record Updates

Last Update Posted (Estimated)

December 15, 2023

Last Update Submitted That Met QC Criteria

December 10, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GASTO-1080

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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