Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

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Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Amino Acids

Mitogens

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants were under prescription of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) at the beginning and continued until disease progressed.

After the first month of EGFR TKI orally, participants were given Stereotactic Body Radiation Therapy (SBRT) in dose of 50 Gy/5 F or 60 Gy/8 F for peripheral and central primary tumor, respectively, combined with oral EGFR TKI continually until the primary end point.

Oral EGFR TKI begins on day 1 and continues until disease progresses.

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

Participants were given Stereotactic Body Radiation Therapy in a dose of 60 Gy/8 fraction for the central tumor or 50 Gy/5 fraction for the peripheral lung cancer, respectively.

Stereotactic Body Radiation Therapy

Dongqing Lv, MD

Haihua Yang, MD

Hailing Xu, MM

Non-small cell lung cancer (NSCLC) is a prevalent disease with high mortality and morbidity, particularly of adenocarcinoma in Asians. Fortunately, with the development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), treatment of lung cancer usher in a new era, resulting in a hit of precise therapy and molecule sequencing. However, it is inevitable for patients to gain acquired resistance of EGFR TKI. Several studies have been demonstrated that there were approximately 30% heterogeneous cells in primary tumors. And emerging studies illuminated that main pattern of treatment failure was the recurrence of primary site. Moreover, it was proved that despite of the drug-resistance cells in progressive site, continual prescription of EGFR TKI in oligometastasis lung cancer could make a difference for patients in progression free survival (PFS) and overall survival (OS), owing to the residual responsive cells in another sites. Therefore, to explore an unique method to control heterogeneous cells in primary site so as to delay or prevent acquired resistance when taking EGFR TKI orally may be of great benefit and therapy.

It is known to all that stereotactic body radiation therapy (SBRT), with the advantage of hypofractionation and rapid release, succeed in several cancers, such as early lung cancer, prostatic, liver cancer and so on, for local control. Numerous reports explained SBRT played an irreplaceable role in progressive NSCLC patients after oral targeted medicine, regardless of EGFR or anaplastic lymphoma kinase (ALK) mutation. And the radiosensitivity of EGFR TKI in vitro and vivo may account for these inspiring results. What's more, it has reported that SBRT could induce inflammatory cell death, activate dendritic cell as well as accelerate antigen presentation in the draining lymph node, leading to antigen-specific adaptive immune response. Nevertheless, although the potential effects of SBRT on advanced NSCLC are obviously, few studies explore the preventive benefits of early SBRT combined with oral EGFR TKI on advanced lung cancer by eliminating the heterogeneous cells in primary site. In addition, the investigators' previous phase II study of SBRT combined with oral EGFR TKI had revealed its safety and potentially improvement of PFS for 6 months.

In this trial, the investigators put sight into assessing the efficacy of early application of SBRT to primary site in the advanced NSCLC patients and provide a hypothesis that early SBRT could strengthen the anti-tumor effect of EGFR TKI through eradicating the heterogenity of initial tumor cells.

Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Combined With Early Stereotactic Body Radiation Therapy to the Primary Tumor in Advanced Non-small Cell Lung Cancer

A Randomized Ⅲ Phase Trial of Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Combined With Early Stereotactic Body Radiation Therapy to the Primary Tumor in Advanced Non-small Cell Lung Cancer Patients Harboring Epidermal Growth Factor Receptor Mutation

Evaluate the effect of EGFR TKI with or without SBRT on progression free survival.

To describe the rate of local control and out-of-field disease progression, irrespectively.

To evaluate overall survival in EGFR TKI therapy with SBRT in comparison to EGFR TKI therapy alone.

The acute and chronic profile associated with the study regimen using CTCAE v5.0.

Haihua Yang

the head of radiotherapy department in Taizhou Hospital

Antineoplastic Agents

Micronutrients

Hematinics

Vitamins

Docetaxel

Pemetrexed

Gefitinib

Tubulin Modulators

Antimitotic Agents

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

combined group chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycle is 6 depending on disease evaluation and patient's physical condition combined with gefitinib 250mg once per day from the start day of chemotherapy until disease progression or intolerable side effects.

sequenced group chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycles is 6 depending on disease evaluation or patient's physical condition sequenced by gefitinib 250mg once per day until disease progression or intolerable side effects.

chemotherapy with docetaxel 75mg/m2 d1 or pemetrexed 500mg/m2 d1, every 3 weeks,at least 2 cycles and the maximal cycle is 6 depending on disease evaluation and patient's physical condition combined with gefitinib 250mg once per day from the start day of chemotherapy until disease progression or intolerable side effects.

combined group

Sequenced group

Mengzhao Wang, MD

Jing Zhao, MD

Wei Zhong, MD

There are two different treatment modes for NSCLC patients who failed to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) after initially responding to EGFR-TKI. One is EGFR-TKI combined with chemotherapy and the other is chemotherapy followed by EGFR-TKI. It is unclear which one is more suitable to this group of lung cancer patients. So this phase Ⅱclinical trial is designed to compare the efficiency and safety of these two different treatment modes.

Responses to EGFR-TKIs are quiet dramatic and durable, especially in patients with EGFR gene classic mutations, such as 19 deletion or 21 leucine 858 arginine(L858R). However, most patients with NSCLC who respond to EGFR-TKIs eventually experience progression of disease after approximately 12 months. The lack of an established therapeutic option for NSCLC patients who have progressive disease after EGFR-TKIs failure poses a great challenge to physicians in terms of how best to manage this growing group of lung cancer patients.

In clinical practice some of the initially EGFR-TKI sensitive tumors which progressed evidence a striking increase in tumor volume within several weeks, after being taken off EGFR-TKI. This response is called "rebound phenomenon". Most experts still believe that these tumors continue to be "oncogene-addicted" to EGFR. So it is rational that EGFR-TKI combined with another chemotherapy regimen can be used to treat NSCLC after the failure of EGFR-TKI therapy.

However in some phase Ⅱclinical trials involved a few NSCLC patients who failed to EGFR-TKI therapy, another treatment mode, that is to say, at least one cytotoxic chemotherapy was used firstly then switched to EGFR-TKI therapy until progression of disease, was used and called reintroduction or retreatment of EGFR-TKI. Using this treatment mode, some investigators reported the partial remission (PR) and disease control rate (DCR) were observed in 21.7%-36% and 65.2%-86% NSCLC patients.

Study of Chemotherapy Sequenced by or Combined With EGFR-TKIs for NSCLC Patients Failed to EGFR-TKIs Therapy

A Phase Ⅱ Randomized Controlled Trial to Compare Chemotherapy Sequenced by EGFR-TKIs and Chemotherapy Combined With EGFR-TKIs for Advanced or Metastatic NSCLC Patients Failed to EGFR-TKIs Therapy

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks.

From date of randomization until the date of death from any cause, assessed up to 100 weeks.

The objective response rate includes the complete remission and partial remission rate.

FACL-L is assessed at different time points.(Date of randomization,1 week after chemotherapy,every cycle of chemotherapy,every month of EGFR-TKI maintain treatment,up to 100 weeks)

The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria(version3.0) (NCI-CTC).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Combined With Early Stereotactic Body Radiation Therapy to the Primary Tumor in Advanced Non-small Cell Lung Cancer	NCT03727867	Advanced Non-sm...	Epidermal Growt... Stereotactic Bo...	18 Years - 85 Years	Taizhou Hospital
Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Combined With Early Stereotactic Body Radiation Therapy to the Primary Tumor in Advanced Non-small Cell Lung Cancer	NCT03727867	Advanced Non-sm...	Epidermal Growt... Stereotactic Bo...	18 Years - 85 Years	Taizhou Hospital
Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Combined With Early Stereotactic Body Radiation Therapy to the Primary Tumor in Advanced Non-small Cell Lung Cancer	NCT03727867	Advanced Non-sm...	Epidermal Growt... Stereotactic Bo...	18 Years - 85 Years	Taizhou Hospital
Study of Chemotherapy Sequenced by or Combined With EGFR-TKIs for NSCLC Patients Failed to EGFR-TKIs Therapy	NCT01746277	Non Small Cell ...	combined group Sequenced group	18 Years - 75 Years	Peking Union Medical College Hospital

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