NSCLC Isotoxic Hypofractionated Chemoradiotherapy (IHRC)

A Phase II Open-Label Multi-center Trial of Isotoxic Hypofractionated Chemoradiotherapy for NSCLC

Radiotherapy plays an important role in non-small cell lung cancer (NSCLC), and concurrent chemoradiation is considered to be the standard treatment for locally advanced NSCLC. However, due to the patient's physical condition, comorbidities and other reasons, only about 1/3 of patients can receive concurrent chemoradiation. Radiotherapy alone or sequential chemoradiation has become the treatment protocol for most patients. Hypofractionated radiotherapy can be used in NSCLC because it can shorten the over treatment time and may potentially reduce the effect of accelerated repopulation and obtain higher biological effective dose（BED）. So far, the vast majority of radiotherapy prescriptions have given a uniform dose of 60 Gy. This unified prescription dosage approach is completely inconsistent with the concept of precision treatment. The Netherlands MAASTRO put forward the concept of in silico radiotherapy prescription, that is: the normal tissue limits are uniform, such as: V20% ≤ 30%, spinal cord V0> 45Gy, etc., and each patient receives a different dose of radiation therapy. This radiation prescription could reach the limits of the normal tissue of every patient; if no one tissue limits were reached, the highest dose was set up to 79.2 Gy (1.8 Gy, BID). MAASTRO applied this "iso-toxic" radiotherapy prescription and used accelerated hyperfractionation technology so that each patient received the maximum individualized radiation dose as possible. We will integrate this concept with hypofractionated radiotherapy in order to further improve efficacy.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Radiation: isotoxic hypofractionated group

Detailed Description

Radiotherapy plays an important role in non-small cell lung cancer (NSCLC), and concurrent chemoradiation is considered to be the standard treatment for locally advanced NSCLC. However, due to the patient's physical condition, comorbidities and other reasons, only about 1/3 of patients can receive concurrent chemoradiation. Radiotherapy alone or sequential chemoradiation has become the treatment protocol for most patients. Hypofractionated radiotherapy can be used in NSCLC because it can shorten the total treatment time and may potentially reduce the effect of accelerated repopulation and obtain higher BED. So far, the vast majority of radiotherapy prescriptions have given a uniform dose of radiotherapy to all patients, regardless of individual factors such as tumor size, location, and adjacent vital organs, which may cause two consequences: First, small-volume tumors may, not receive enough radiation dose, resulting in a decrease in local control rate. Second, for large volumes of tumors or tumors adjacent to vital organs, even the "so-called" standard dose (60 Gy) may cause serious damage to normal tissues. This unified prescription dosage approach is completely inconsistent with the concept of precision treatment. The Netherlands MAASTRO put forward the concept of in silico radiotherapy prescription, that is: the normal tissue limits are uniform, such as: V20% ≤ 30%, spinal cord V0> 45Gy, etc., and each patient receives a different dose of radiation therapy.This radiation prescription could reach the limits of the normal tissue of every patient; if no one tissue limits were reached, the highest dose was set up to 79.2 Gy (1.8 Gy, BID). MAASTRO applied this "iso-toxic" radiotherapy prescription and used accelerated hyperfractionation technology so that each patient received the maximum individualized radiation dose as possible.From the model study to the long-term survival results, a series of encouraging results were achieved. The use of an individualized radiotherapy prescription based on iso-toxicity for the treatment of NSCLC in large-segment radiotherapy is expected to achieve: 1. For patients with small tumor volumes and no adjacent to vital organs, a higher radiation dose is given under safe conditions. 2. For patients with larger volumes of tumors or adjacent to vital organs, give safer doses.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiao-Ying Xue, Professor; Phone Number: +86-158-0321-0636; Email: xxy0636@163.com

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Recruiting
      • The Second Hospital of Hebei Medical University
      • Contact: Xiao-Ying Xue, Professor; Phone Number: +86-158-0321-0636; Email: xxy0636@163.com
      • Contact: Lin, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Pathological or cytological diagnosis of non-small cell lung cancer patients, the clinical stage using the eighth edition of American Joint Committee on Cancer（AJCC）, including stage III without resectable or who when SBRT/SABR are not suitable;
2. Age ≥ 18 years，≤ 75 years;
3. The expected survival period is ≥ 3 months;
4. Karnofsky performance status （KPS） score ≥ 60;
5. Normal blood account , liver and kidney function;
6. Forced expiratory volume in 1 second of 0.75 L or greater.

Exclusion Criteria:

1. Serious medical problems require hospitalization, include (but not limited to ): history of pulmonary fibrosis, previous myocardial infarction within 6 months, heart failure grade II and above, uncontrolled heart failure, uncontrolled chronic obstructive pulmonary disease （COPD）, uncontrolled diabetes .et al;
2. Esophageal invasion (cT4);
3. Others are not suitable for receiving radiotherapy and chemotherapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: isotoxic hypofractionated group; Hypofractionated radiation: 1. Split mode: 3Gy/f. 2,Individualized prescriptions for different patients: (1) Spinal cord: 0%>45 Gy, and ≤2 Gy each time Lung: V20≤30%, V5≤65%, MLD≤16Gy Esophagus: highest dose ≤ 69Gy 3. Maximum limit: If the limit of any "A" is not reached, the maximum radiation dose is 69 Gy. The lowest radiation dose: 45Gy. Chemotherapy: Platinum-containing two-drug regimen: docetaxel + lobaplatin: Docetaxel 60 mg/m2, d1; Lobaplatin 30 mg/m2, d1; repeated every 28 days. The first cycle of chemotherapy started on the first day of radiotherapy. The same chemotherapy regimen is used up to 4 cycles as consolidation after the completion of radiotherapy.

Radiation: isotoxic hypofractionated group; the normal tissue limits are uniform, such as: V20% ≤ 30%, spinal cord 0> 45Gy, etc., and used hypofractionated radiotherapy technology so that each patient received the maximum individualized radiation dose as possible，and the same time use the Platinum-containing drugs: docetaxel + lobaplatin Docetaxel 60 mg/m2, d1; Lobaplatin 30 mg/m2, d1, repeated every 28 days. The first cycle of chemotherapy started on the first day of radiotherapy.Consolidate chemotherapy up to 4 cycles after radiotherapy, as above.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
radiation induced esophagitis and radiation induced pneumonitis	Number of participants with treatment-related severe adverse events：Grade IV radiation esophagitis, Grade III radiation esophagitis which results in interruption of radiotherapy for 7 days or more, and Grade III or above radiation pneumonitis	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to disease progression (TTP)	Record the time from the start of enrollment to the objective progression of the tumor	5 years
progression-free survival(PFS)	Record the time from the start of enrollment to the progression of disease or death	5 years
overall survival (OS)	Record the time from the start of enrollment to progression or primary tumors	5 years
local control（LC）	record the proportion of no increase in primary tumor	5 years

Collaborators and Investigators

• Sponsor: The Second Hospital of Hebei Medical University
• Investigators: Study Chair: Xiao-Ying Xue, Professor, The Second Hospital of Hebei Medical University; Study Director: Qiang Lin, Professor, North China Petroleum Bureau General Hospital, Hebei Medical University; Study Director: Chao-Xing Liu, Professor, No.1 Hospital of Shijiazhuang City

Publications and helpful links

General Publications

• Liu YE, Xue XY, Zhang R, Chen XJ, Ding YX, Liu CX, Qin YL, Li WQ, Ren XC, Lin Q. Study protocol: a multicentre, prospective, phase II trial of isotoxic hypofractionated concurrent chemoradiotherapy for non-small cell lung cancer. BMJ Open. 2020 Oct 23;10(10):e036295. doi: 10.1136/bmjopen-2019-036295.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2026

Study Registration Dates

• First Submitted: June 27, 2018
• First Submitted That Met QC Criteria: July 21, 2018
• First Posted (Actual): July 30, 2018

Study Record Updates

• Last Update Posted (Actual): May 9, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: isotoxic; hypofractionated radiotherapy; Non-Small-Cell Lung
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: NSCLS isotoxic HypoRCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

After the publication of this study, we could share the IPD. However, this sharing is limited to academic research.

Person to be contacted: Study Chair: Professor Xiao Ying Xue. Contact information: zyy_lq@petrochina.com.cn

• IPD Sharing Time Frame: After the publication of this study, we could share the IPD
• IPD Sharing Access Criteria: However, this sharing is limited to academic research. Person to be contacted: Study Chair: Professor Xiao Ying Xue.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No