Targeted Treatment With Intercalated Radiotherapy in EGFR-mutant IIIA/IIIB NSCLC

Non-small Cell Lung Cancer Clinical Trial

— TREND  

Official title:

Intercalated Combination of Erlotinib and Radiotherapy for Patients With EGFR-mutant, Unresectable, Locally Advanced Non-small-cell Lung Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03074864
• Other study ID #: TREND
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• First received: February 27, 2017
• Last updated: March 5, 2017
• Start date: February 27, 2017
• Est. completion date: June 30, 2020

Study information

• Verified date: March 2017
• Source: Guangdong General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to investigate the efficacy and safety of intercalated combination of erlotinib and radiotherapy for patients with EGFR-mutant, unresectable, locally advanced NSCLC, and to explore a new treatment strategy for this subset. After Induction by erlotinib, local radiotherapy is intercalated, and followed by 24-week erlotinib maintenance.

Description:

Chemoradiation therapy is the standard treatment for unresectable, locally advanced NSCLC, but its efficacy reaches a platform, and treatment-related life threatening toxicity limits its use. The EGFR tyrosine kinase inhibitors (TKIs) produce a dramatic response in patients carrying EGFR activating mutations in the metastatic setting. Multiple prospective trials show that EGFR-TKIs have a better tolerability when compared with chemotherapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Males or females aged =18 years.

2. ECOG performance status 0-2.

3. Pathologically diagnosed of non-small cell lung cancer, and staged as unresectable IIIA/IIIB according the TNM staging system (2009).

4. EGFR activating mutations in exon 18, 19 or 21were detected in tumor tissue or plasma.

5. Measurable disease must be characterized according to RECIST 1.1 criteria.

6. Life expectancy =12 weeks.

7. Adequate pulmonary function: FEV1.0 >50% of the normal predicted value, or DLCO >40% of the normal predicted value.

8. Adequate liver function: Total bilirubin = 1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST), alanine aminotransferase (ALT) = 3.0 x ULN in subjects without liver metastases; = 5 x ULN in subjects with liver metastases.

9. Adequate renal function: serum creatinine = 1. 5 x ULN, and creatinine clearance = 45 ml/min.

10. Adequate hematological function: Absolute neutrophil count (ANC) =1.0 x 109/L, and Platelet count =75 x 109/L, and Hemoglobin =8 g/dL.

11. Female subjects should not be pregnant or breast-feeding.

12. Written informed consent provided.

13. Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.

Exclusion Criteria:

1. Histologically mixed with small-cell lung cancer.

2. Mutations in EGFR exon 20 are detected.

3. Exposure to prior chest irradiation before the enrollment.

4. Patients with prior chemotherapy or agents directed at the HER axis (e.g. erlotinib, gefitinib, cetuximab, trastuzumab).

5. History of another malignancy in the last 5 years with the exception of the following: Other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted; Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.

6. Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).

7. Existence of interstitial lung disease.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Epidermal Growth Factor Receptor
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Erlotinib Hydrochloride
Subjects receive erlotinib tablet 150mg orally once daily, after 12 weeks of induction phase, local radiotherapy is intercalated, and followed by 24-week erlotinib maintenance phase. At the end of maintenance, the subjects enter into the follow-up period.

Locations

Country	Name	City	State
China	Guangdong General Hospital	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Guangdong General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quality of Life (QOL)	To evaluate the Quality of Life (QOL) of subjects during treatment.	Questionnaire of QOL will be recorded for up to 24 weeks.
Primary	Objective response rate	assessed by the RECIST 1.1 criteria	Tumor response will be evaluated through study completion, an average of 6 weeks.
Secondary	1 year survival rate	To evaluate the 1 year survival rate of the new strategy.	Pts after maintenance phase will receive long-term follow-up including CT scan every 12 weeks for up to 10 years.
Secondary	3 year survival rate	To evaluate the 3 year survival rate of the new strategy.	Pts after maintenance phase will receive long-term follow-up including CT scan every 12 weeks for up to 10 years.
Secondary	Progression free survival(PFS)	The product limit estimator developed by Kaplan and Meier will be used.	Occurrence of local or regional progression, distant metastases, or death from any cause from the time of treatment to the occurrence of one of the failure events, whichever occurs first, assessed up to 10 years.
Secondary	Overall survival	The product limit estimator developed by Kaplan and Meier will be used. Their 95% confidence intervals will be estimated.	Time from treatment to death from any cause, assessed up to 10 years.