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

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ClinicalTrials.gov Identifier: NCT02929693
Recruitment Status : Enrolling by invitation
First Posted : October 11, 2016
Last Update Posted : April 11, 2019
Sponsor:
Collaborators:
Shanghai Chest Hospital
Shanghai Pulmonary Hospital, Shanghai, China
Information provided by (Responsible Party):
Ling Xu, Shanghai University of Traditional Chinese Medicine

Brief 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).

Condition or disease Intervention/treatment Phase
Cancer Drug: gefitinib Drug: Yiqi-yangyin-jiedu decoction Drug: placebo Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 198 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clinical Study of Yiqi-yangyin-jiedu Decoction Combined With Gefitinib in Advanced Pulmonary Adenocarcinoma Patients With Activating EGFR Mutation
Study Start Date : October 2016
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Gefitinib

Arm Intervention/treatment
Experimental: combination
YYJD plus gefitinib
Drug: gefitinib
250 mg oral once a day until progression or unacceptable toxicity develops
Other Name: Iressa

Drug: 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.
Other Name: YYJD

Placebo Comparator: controll
placebo plus gefitinib
Drug: gefitinib
250 mg oral once a day until progression or unacceptable toxicity develops
Other Name: Iressa

Drug: 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.
Other Name: control




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 2 months ]
    Time from start of the study treatment to date of objective tumour progression (excluding clinical deterioration without evidence of objective progression).


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 2 months ]
    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. Objective response rate (ORR) [ Time Frame: 2 months ]
    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).

  3. Quality of life (QOL) [ Time Frame: 2 months ]
    QOL is assessed using Functional Assessment of Cancer therapy-lung (FACT-L) questionnaire .

  4. Safety assessment evaluated according to Common Toxicity Criteria [ Time Frame: 2 months ]
    Safety assessment is evaluated according to Common Toxicity Criteria (CTC 3.0).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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;
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Responsible Party: Ling Xu, Principal Investigator, Shanghai University of Traditional Chinese Medicine
ClinicalTrials.gov Identifier: NCT02929693    
Other Study ID Numbers: SHUTCM
First Posted: October 11, 2016    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Adenocarcinoma
Adenocarcinoma of Lung
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Gefitinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action