Clinical trial NCT03606239: NSCLC Isotoxic Hypofractionated Chemoradiotherapy
Official title: A Phase II Open-Label Multi-center Trial of Isotoxic Hypofractionated Chemoradiotherapy for NSCLC
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: isotoxic
hypofractionated radiotherapy
Non-Small-Cell Lung
Lead sponsor: The Second Hospital of Hebei Medical University
Sponsor class: OTHER
First posted: 2018-07-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: radiation induced esophagitis and radiation induced pneumonitis
timeFrame: 2 years
Secondary outcomes:
measure: time to disease progression (TTP)
timeFrame: 5 years
measure: progression-free survival(PFS)
timeFrame: 5 years
measure: overall survival (OS)
timeFrame: 5 years
measure: local control（LC）
timeFrame: 5 years
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
Study officials:
affiliation: The Second Hospital of Hebei Medical University
name: Xiao-Ying Xue, Professor
role: STUDY_CHAIR
affiliation: North China Petroleum Bureau General Hospital, Hebei Medical University
name: Qiang Lin, Professor
role: STUDY_DIRECTOR
affiliation: No.1 Hospital of Shijiazhuang City
name: Chao-Xing Liu, Professor
role: STUDY_DIRECTOR
References:
citation: 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.