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

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

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.

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer; Epidermal Growth Factor Receptor
• Intervention / Treatment: Drug: Erlotinib Hydrochloride

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: EGFR-mutant IIIA/IIIB NSCLC; Erlotinib Hydrochloride 150mg daily intercalated with radiotherapy	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.; Other Names: Cp-358,774, OSI-774, Tarceva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	assessed by the RECIST 1.1 criteria	Tumor response will be evaluated through study completion, an average of 6 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital
• Investigators: Principal Investigator: Hua-Jun CHEN, MD, Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 27, 2017
• Primary Completion (ANTICIPATED): June 30, 2019
• Study Completion (ANTICIPATED): June 30, 2020

Study Registration Dates

• First Submitted: February 27, 2017
• First Submitted That Met QC Criteria: March 5, 2017
• First Posted (ACTUAL): March 9, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 9, 2017
• Last Update Submitted That Met QC Criteria: March 5, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Activating mutations,lung cancer,radiotherapy
• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: Trend

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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