Clinical Study of YYJD Decoction Combined With Gefitinib in Advanced Pulmonary Adenocarcinoma

Cancer Clinical Trial

Official title:

Clinical Study of Yiqi-yangyin-jiedu Decoction Combined With Gefitinib in Advanced Pulmonary Adenocarcinoma Patients With Activating EGFR Mutation

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02929693
• Other study ID #: SHUTCM
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: October 2016
• Est. completion date: June 2019

Study information

• Verified date: April 2019
• Source: Shanghai University of Traditional Chinese Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators performed a multi-centered, randomized, double blinded, placebo-controlled, prospective clinical trial on the effect of Yiqi-yangyin-jiedu decoction (YYJD), a chinese herbal medicine (CHM) formula combined with gefitinib to prolong the progression free survival (PFS) of advanced pulmonary adenocarcinoma patients with activating EGFR mutation (exon19del or exon21L858R). The investigators plan to enroll 198 cases in 3 years (99 cases for gefitinib, 99 cases for gefitinib plus YYJD), expecting that combination therapy has a better efficacy on prolonging PFS, overall survival, improving quality of life(QOL).

Description:

Non-Small-Cell Lung Cancer（NSCLC）is one of the malignancies with high incidence and mortality. Epidermal growth factor receptor (EGFR) is implicated in NSCLC pathogenesis. Certain patient subgroups with NSCLC (ie, women, never-smokers, East Asians,adenocarcinoma) have higher rates of EGFR mutations, rendering them more responsive to EGFR tyrosine kinase inhibitors (TKIs; eg, gefitinib, erlotinib, Icotinib). Among patients with advanced EGFR-mutated NSCLC, treatment with EGFR-TKIs is associated with response rates of 56 to 74% and a median progression-free survival(mPFS) of 10 to 14 months;both outcomes are superior to those with platinum-based chemotherapy. Despite initial responses to EGFR-TKIs, the majority of patients will have disease progression within 1 to 2 years after treatment initiation (acquired resistance). In approximately 60% of patients, the mechanism of acquired resistance is the development of an additional EGFR mutation, EGFR T790M. Although AZD9291 (AstraZeneca), a third-generation EGFR-TKI is reported with a response rate of 61% in NSCLC patients with EGFR T790M and a mPFS of 9.6 months, resistance to third-generation inhibitors mediated by EGFR C797S mutation is inevitable. Therefore, optimizing the effect of each generation of EGFR-TKI is essential for long-term survival of NSCLC.The investigators' preliminary studies have shown that combining Yiqi-yangyin-jiedu decoction (YYJD) with gefitinib can prolong PFS and improve QOL, but high-level evidences are needed.

The investigators performed a multi-centered, randomized, double blinded, placebo-controlled, prospective clinical trial on the effect of YYJD, a chinese herbal medicine (CHM) formula combined with gefitinib in advanced pulmonary adenocarcinoma patients with activating EGFR mutation (exon19del or exon21L858R) that choose gefitinib as first-line or second line therapy. Patients are randomized into observational group (YYJD plus gefitinib),and control group (placebo plus gefitinib). The treatment should be continued until evidence of disease progression or unacceptable toxicity, and after that regular follow-up will be arranged. The primary efficacy assessments are: PFS (progression-free survival); Secondary efficacy assessments are: (1) OS (overall survival); (2) Objective response rate; (3) QOL (Functional Assessment of Cancer therapy-lung, FACT-L4.0 scales; Lung Cancer Symptom Scale, LCSS); (4) other efficacy assessments are: 1) TCM symptoms changes; 2) Toxicity, side effects and security of the treatments will be assessed at the same time. The investigators plan to enroll 198 cases in 3 years (99 cases for gefitinib, 99 cases for gefitinib plus YYJD), expecting that combination therapy has a better efficacy on prolonging PFS, overall survival, improving quality of life(QOL). Therefore the study can provide evidences for optimizing and promoting the efficacy of gefitinib.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 198
• Est. completion date: June 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically or cytologically confirmed stage IIIa-IV pulmonary adenocarcinoma;

• With activating EGFR mutation (either exon19del or exon21L858R) and one month of gefitinib as first-line or second-line therapy without disease progression (PD);

• With TCM diagnostic pattern Qin-and-yin dificiency;

• Age =18 years old;

• Estimated life expectancy of at least 12 weeks;

• Without major organ dysfunction: hemoglobin =9 g/dL, absolute neutrophil count (ANC) =1.5*109/L, platelets =100 *109/L,bilirubin =1.5ULN, alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) =2.5 upper limited number(ULN) (AP, AST, ALT =5ULN is acceptable with liver metastasis).INR=1.5, APTT in the normal range( 1.2DLN-1.2ULN),creatinine =1.5ULN;

Exclusion Criteria:

• with other malignant tumor except NSCLC 5 years previous to study entry;

• PD after onee month of gefitinib treatment

• Estimated life expectancy less than 12 weeks;

• Brain metastasis with relevant symptoms

• History of cardiovascular disease: Congestive Heart Failure > grade II in NYHA.Unstable angina patients (have angina symptoms in rest) or a new occurrence of angina (began in the last 3 months) or myocardial infarction happens in the last 6 months;

• Pregnant or child breast feeding women;

• Mental or cognitive disorders;

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Cancer

Intervention

Drug:
• gefitinib
250 mg oral once a day until progression or unacceptable toxicity develops
• Yiqi-yangyin-jiedu decoction
Yiqi-yangyin-jiedu decoction is a traditional chinese herbal medicine formula,and should be taken one package, twice a day, until progression or unacceptable toxicity develops.
• placebo
Oral granules, which the taste and smell are similar to YYJD, has no therapeutic effect, Oral granules, which the taste and smell are similar to experimental TCM granules, has no therapeutic effect, one package, twice a day, until progression or unacceptable toxicity develops.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Shanghai University of Traditional Chinese Medicine	Shanghai Chest Hospital, Shanghai Pulmonary Hospital, Shanghai, China

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	Time from start of the study treatment to date of objective tumour progression (excluding clinical deterioration without evidence of objective progression).	2 months
Secondary	Overall survival (OS)	interval time from the first date of randomization to that of death for any reason, the end of the study, or loss of follow-up	2 months
Secondary	Objective response rate (ORR)	The ORR (complete response (CR) plus partial response (PR)) was determined by the Response Evaluation Criteria In Solid Tumors (RECIST) (Eisenhauer et al, 2009) version 1.1.in Solid Tumors (RECIST1.1).	2 months
Secondary	Quality of life (QOL)	QOL is assessed using Functional Assessment of Cancer therapy-lung (FACT-L) questionnaire .	2 months
Secondary	Safety assessment evaluated according to Common Toxicity Criteria	Safety assessment is evaluated according to Common Toxicity Criteria (CTC 3.0).	2 months