Back to resultsIMRT and Timing in Combination With EGFRTKI for Stage IV Non-small-cell Lung Cancer
Primary Purpose
Non-Small Cell Lung Cancer, Nonsmall Cell Lung Cancer, Carcinoma, Non-Small-Cell Lung
Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
EGFR-TK Inhibitor
Intensity Modulated Radiation Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed stage IV NSCLC[UICC 2017 8th edition] with known sensitive EGFR mutations(confirmed by tissue or blood).
- Have not received one or more prior treatments
- 18 to 80 years of age.ECOG performance status 0～2 or KPS≥60
- Have distant metastatic lesions≤5；and have clear consciousness when the metastatic sites were brain; and have no influence on pulmonary function when the metastatic sites were lung.
- Have no contraindications in radiotherapy, EGFR-TKI and chemotherapy
- Normal bone marrow and organ function as defined below:
Absolute neutrophil count ≥ 1,500/mcl Platelets ≥ 100,000/mcl Hemoglobin ≥ 9.0 g/dL Total bilirubin ≤ 2.0 x IULN AST (SGOT) / ALT (SGPT) ≤ 3.0 x IULN; if liver metastases, ≤ 5.0 x IULN Serum creatinine ≤ 1.5 x ULN LVEF ≥ 50% performed no more than 4 weeks prior to enrollment. FEV1>50%，mild-moderate pulmonary function dysfunction.
- Able to understand and willing to sign a Human Research Protection Office (HRPO) approved written informed consent document (or that of legally authorized representative, if applicable).
- With good compliance to the treatment and Follow-up
Exclusion Criteria:
- Evidence of small cell, large cell neuroendocrine or carcinoid histology.
- Non-stage IV NSCLC and ECOG performance status 3～5 or KPS<60
- Have a serious or uncontrolled medical condition that could compromise the patients' ability to adhere to the protocol.
- Malignant pleural effusion and pericardial effusion
- Uncontrolled intercurrent illness including, but not limited to, hypertension , diabetes mellitus ,ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and/or breastfeeding: Patient must have a negative pregnancy test within 14 days of study entry.
- Have a secondary malignancy (except adequately treated non-melanomatous skin cancer, or other cancer such as in situ of the cervix. considered cured by surgical resection or radiation). Patients who have had another malignancy in the past but have been disease free for more than 5 years are eligible.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to EGFR-TKI or other agents used in the study.
- With poor compliance
- The researchers consider it inappropriate to participate in the study
Sites / Locations
- The affiliated hospital of Guizhou medical university
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Mutation+ concurrent
Mutation+ concomitant
Arm Description
IMRT concurrent with EGFR-TKI on paticipants with known sensitive EGFR mutations.
IMRT concomitant with EGFR-TKI on paticipants with known sensitive EGFR mutations.
Outcomes
Primary Outcome Measures
Therapeutic efficacy of EGFR-TKI and concurrent/concomitant local RT in NSCLC patients.
Tumor Response will be evaluated using the RECIST system. Modified WHO criteria will be used for measurement of tumors. The irradiated lesion will be excluded from the assessment of response.
Overall survival (OS)
Overall survival is defined as the time interval from date of diagnosis to date of death from any cause
Progression-free survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Progressive disease (PD) = at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, appearance of one or more non-target lesion(s) and/or unequivocal progression of existing non-target lesions
Secondary Outcome Measures
Objective response rate(ORR)
Partial response + complete response per RECIST 1.1 criteria Complete response (CR) = disappearance of all target lesions, non-target lesions, and normalization of tumor marker level
Partial response (PR) = at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline of sum diameters
Disease control rate (DCR)
Percentage of patients who achieve complete response, partial response, or stable disease per RECIST 1.1 criteria.
Complete response (CR) = disappearance of all target lesions, non-target lesions, and normalization of tumor marker level
Partial response (PR) = at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline of sum diameters
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Adverse events (toxicities)
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Local regional progression-free survival（LRPFS）
LRPFS is defined as the duration of time from start of treatment to time of progression or recurrence, whichever occurs first..The target lesions is only for primary tumor and regional positive lymph nodes.
Progressive disease (PD) = at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, appearance of one or more target lesion(s) and/or unequivocal progression of existing target lesions.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03258671
Brief Title
IMRT and Timing in Combination With EGFRTKI for Stage IV Non-small-cell Lung Cancer
Official Title
IMRT and Timing in Combination With EGFRTKI for Stage IV Non-small-cell Lung Cancer: Results of a Randomised,Openlabel,Multicentre Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Unknown status
Study Start Date
October 1, 2017 (Anticipated)
Primary Completion Date
December 30, 2020 (Anticipated)
Study Completion Date
December 30, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
LuBing
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is for patients with EFGR gene sensitive mutations diagnosed by pathology or cytology, having a course of chest radiotherapy treatment and molecular Target Therapy for the treatment of stage IV non-small cell lung cancer. Patients with non-small cell lung cancer have a risk of the tumour in the lung recurring or progressing after treatment.
In this study, the investigators aim to verify the following hypothesis:
whether in combination with concurrent or concomitant EGFR-TKI regimen chemotherapy, Intensity Modulated Radiation Therapy can reduce the risk of the tumour in the lung recurring or progressing similarily.
Intensity Modulated Radiation Therapy concomitant with EGFR-TKI has a better normal tissue dose/volume tolerance than concurrent regimen.
the survival can be improved by using this new molecular Target-radiotherapy method.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer, Nonsmall Cell Lung Cancer, Carcinoma, Non-Small-Cell Lung
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
160 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Mutation+ concurrent
Arm Type
Experimental
Arm Description
IMRT concurrent with EGFR-TKI on paticipants with known sensitive EGFR mutations.
Arm Title
Mutation+ concomitant
Arm Type
Experimental
Arm Description
IMRT concomitant with EGFR-TKI on paticipants with known sensitive EGFR mutations.
Intervention Type
Drug
Intervention Name(s)
EGFR-TK Inhibitor
Intervention Description
·EGFR-TKI：gefitinib will be administered 250mg/d ivgtt qd; icotinib will be administered 150mg/d ivgtt tid;
Intervention Type
Radiation
Intervention Name(s)
Intensity Modulated Radiation Therapy
Intervention Description
High dose group：DTGTV=70Gy；
first course radiotherapy：40Gy/20f/4w（DTPTV：36Gy/20f/4w）,2Gy/f/d；
late course radiotherapy：1.5Gy/f、2f/d、interval≥6 hs、DTGTV=30Gy（DTPTV=27Gy）。
Low dose group：DTGTV=50Gy;
first course radiotherapy：32Gy/16f/3w（DTPTV为28.8Gy/16f/3w），2Gy/f/d；
late course radiotherapy：1.5Gy/f、2f/d、interval≥6小时、DTGTV为18Gy（DTPTV为16.2Gy）。
Primary Outcome Measure Information:
Title
Therapeutic efficacy of EGFR-TKI and concurrent/concomitant local RT in NSCLC patients.
Description
Tumor Response will be evaluated using the RECIST system. Modified WHO criteria will be used for measurement of tumors. The irradiated lesion will be excluded from the assessment of response.
Time Frame
>4 weeks post treatment
Title
Overall survival (OS)
Description
Overall survival is defined as the time interval from date of diagnosis to date of death from any cause
Time Frame
Up to 5 years
Title
Progression-free survival (PFS)
Description
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Progressive disease (PD) = at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, appearance of one or more non-target lesion(s) and/or unequivocal progression of existing non-target lesions
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Objective response rate(ORR)
Description
Partial response + complete response per RECIST 1.1 criteria Complete response (CR) = disappearance of all target lesions, non-target lesions, and normalization of tumor marker level
Partial response (PR) = at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline of sum diameters
Time Frame
Up to 5 years
Title
Disease control rate (DCR)
Description
Percentage of patients who achieve complete response, partial response, or stable disease per RECIST 1.1 criteria.
Complete response (CR) = disappearance of all target lesions, non-target lesions, and normalization of tumor marker level
Partial response (PR) = at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline of sum diameters
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame
Up to 5 years
Title
Adverse events (toxicities)
Description
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Time Frame
Up to 5 years
Title
Local regional progression-free survival（LRPFS）
Description
LRPFS is defined as the duration of time from start of treatment to time of progression or recurrence, whichever occurs first..The target lesions is only for primary tumor and regional positive lymph nodes.
Progressive disease (PD) = at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, appearance of one or more target lesion(s) and/or unequivocal progression of existing target lesions.
Time Frame
Time Frame: Up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed stage IV NSCLC[UICC 2017 8th edition] with known sensitive EGFR mutations(confirmed by tissue or blood).
Have not received one or more prior treatments
18 to 80 years of age.ECOG performance status 0～2 or KPS≥60
Have distant metastatic lesions≤5；and have clear consciousness when the metastatic sites were brain; and have no influence on pulmonary function when the metastatic sites were lung.
Have no contraindications in radiotherapy, EGFR-TKI and chemotherapy
Normal bone marrow and organ function as defined below:
Absolute neutrophil count ≥ 1,500/mcl Platelets ≥ 100,000/mcl Hemoglobin ≥ 9.0 g/dL Total bilirubin ≤ 2.0 x IULN AST (SGOT) / ALT (SGPT) ≤ 3.0 x IULN; if liver metastases, ≤ 5.0 x IULN Serum creatinine ≤ 1.5 x ULN LVEF ≥ 50% performed no more than 4 weeks prior to enrollment. FEV1>50%，mild-moderate pulmonary function dysfunction.
Able to understand and willing to sign a Human Research Protection Office (HRPO) approved written informed consent document (or that of legally authorized representative, if applicable).
With good compliance to the treatment and Follow-up
Exclusion Criteria:
Evidence of small cell, large cell neuroendocrine or carcinoid histology.
Non-stage IV NSCLC and ECOG performance status 3～5 or KPS<60
Have a serious or uncontrolled medical condition that could compromise the patients' ability to adhere to the protocol.
Malignant pleural effusion and pericardial effusion
Uncontrolled intercurrent illness including, but not limited to, hypertension , diabetes mellitus ,ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant and/or breastfeeding: Patient must have a negative pregnancy test within 14 days of study entry.
Have a secondary malignancy (except adequately treated non-melanomatous skin cancer, or other cancer such as in situ of the cervix. considered cured by surgical resection or radiation). Patients who have had another malignancy in the past but have been disease free for more than 5 years are eligible.
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to EGFR-TKI or other agents used in the study.
With poor compliance
The researchers consider it inappropriate to participate in the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lu Bing, Director
Phone
86-18275356814
Email
ouyangww103173@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lu Bing, Director
Organizational Affiliation
ouyangww103173@163.com
Official's Role
Study Director
Facility Information:
Facility Name
The affiliated hospital of Guizhou medical university
City
Guiyang
State/Province
Guizhou
ZIP/Postal Code
550004
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lu Bing, MD
Phone
86-18275356814
Email
ouyangww103173@163.com
12. IPD Sharing Statement
Citations:
PubMed Identifier
34631535
Citation
Li Q, Liang N, Zhang X, Zhang Y, Ouyang W, Su S, Ma Z, Hu Y, Geng Y, Chen X, Lu B. Reasonable Timing of Radiotherapy for Stage IV Non-Small-Cell Lung Cancer During Targeted Therapy Based on Tumour Volume Change. Front Oncol. 2021 Sep 23;11:705303. doi: 10.3389/fonc.2021.705303. eCollection 2021.
Results Reference
derived
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IMRT and Timing in Combination With EGFRTKI for Stage IV Non-small-cell Lung Cancer
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