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Report for Clinical Trial NCT03394118

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase II Study for Evaluating Anti-tumor Efficacy of TAGRISSO (Osimertinib) in NSCLC Patients in Whom T790 Mutations Are Detected by Liquid Biopsy Using Bronchoalveolar Lavage Fluid, Plasma or Pleural Effusion

In this trial, anti-tumor efficacy of TAGRISSO in NSCLC patients in whom T790 mutations are detected by liquid biopsy.

NCT03394118 NSCLC
MeSH:Pleural Effusion
HPO:Pleural effusion

1 Interventions

Name: Osimertinib

Description: A cycle of study treatment is defined as 28 days. Each subject will continue the study drug(Osimertinib) until disease progression or manifestation of unacceptable toxicity during the study period. The study drug will be administered orally as one 80 mg tablet once a day. The initial dose of the study drug 80 mg daily can be reduced to 40 mg once daily.
Type: Drug
Group Labels: 1

Group_TAGRISSO


Primary Outcomes

Description: Objective response rate (ORR) including rate of CR and PR on based of RECIST 1.1

Measure: ORR

Time: through study completion (43 months)

Secondary Outcomes

Description: Disease control rate (DCR) including rate of CR, PR and SD on based of RECIST 1.1

Measure: DCR

Time: through study completion (43 months)

Description: Progression-free survival (PFS) the time from first dose of the study drug until the date of disease progression or death by any cause.

Measure: PFS

Time: through study completion (43 months)

Measure: T790M postive rate in Plasma cell free DNA

Time: through study completion (43 months)

Measure: T790M postive rate in BALF free DNA

Time: through study completion (43 months)

Measure: T790M postive rate in tissue

Time: through study completion (43 months)

Measure: Concordance rate of T790M positivity between plasma & BALF

Time: through study completion (43 months)

Measure: T790M sensitivity & specificity in Plasma & BALF (gold standard: tissue biopsy)

Time: through study completion (43 months)

Description: AE/SAE assessement on the base of NCI-CTCAE (version 4.03).

Measure: The frequency of occurrence of grade 3 or higher AE/SAEs

Time: through study completion (43 months)

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There are 3 SNPs

SNPs


1 L858R

AE/SAE assessement on the base of NCI-CTCAE (version 4.03).. Inclusion Criteria: 1. Age ≥ 20, and patients who understand information about the trial and voluntarily agree to participate in the trial 2. Histological or cytological confirmation diagnosis of NSCLC and inoperable stage IIIB or IV at the time of study enrolment 3. Patients with EGFR sensitizing mutation (E19Del, L858R, L861Q, G719X) positive, who had shown clinical benefits (responders (CR or PR) and SD ≥6 months) from EGFR-TKIs and had developed progressive disease following those therapy - Patients who have histories of previous exposure to EGFR-TKIs or other systemic chemotherapies are permitted (regardless of the order of treatment) - Treated with at least one of KGFR-TKIs (regardless of treatment with or without systemic chemotherapies) - In case the patient previously received any of the treatments including systemic chemotherapy, radiation therapy, surgery, and hormonal therapy, there should be at least 2 weeks of time interval between the last day of the previous treatment and the start of TAGRISSO™, and the remaining toxicity should be ≤ CTCAE grade 1 at the time of starting study treatment (except alopecia and grade 2, prior platinum-therapy related neuropathy) 4. ECOG performance status 0-2 5. Patients in whom T790 mutations are detected in at least one of the samples including tumor tissues, BALF (cell-free DNA), plasma (cell-free DNA), and pleural effusion (cell-free DNA) 6. --- L858R ---

Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry Inclusion Criteria: 1. Age ≥ 20, and patients who understand information about the trial and voluntarily agree to participate in the trial 2. Histological or cytological confirmation diagnosis of NSCLC and inoperable stage IIIB or IV at the time of study enrolment 3. Patients with EGFR sensitizing mutation (E19Del, L858R, L861Q, G719X) positive, who had shown clinical benefits (responders (CR or PR) and SD ≥6 months) from EGFR-TKIs and had developed progressive disease following those therapy - Patients who have histories of previous exposure to EGFR-TKIs or other systemic chemotherapies are permitted (regardless of the order of treatment) - Treated with at least one of KGFR-TKIs (regardless of treatment with or without systemic chemotherapies) - In case the patient previously received any of the treatments including systemic chemotherapy, radiation therapy, surgery, and hormonal therapy, there should be at least 2 weeks of time interval between the last day of the previous treatment and the start of TAGRISSO™, and the remaining toxicity should be ≤ CTCAE grade 1 at the time of starting study treatment (except alopecia and grade 2, prior platinum-therapy related neuropathy) 4. ECOG performance status 0-2 5. Patients in whom T790 mutations are detected in at least one of the samples including tumor tissues, BALF (cell-free DNA), plasma (cell-free DNA), and pleural effusion (cell-free DNA) 6. --- L858R ---


2 L861Q

AE/SAE assessement on the base of NCI-CTCAE (version 4.03).. Inclusion Criteria: 1. Age ≥ 20, and patients who understand information about the trial and voluntarily agree to participate in the trial 2. Histological or cytological confirmation diagnosis of NSCLC and inoperable stage IIIB or IV at the time of study enrolment 3. Patients with EGFR sensitizing mutation (E19Del, L858R, L861Q, G719X) positive, who had shown clinical benefits (responders (CR or PR) and SD ≥6 months) from EGFR-TKIs and had developed progressive disease following those therapy - Patients who have histories of previous exposure to EGFR-TKIs or other systemic chemotherapies are permitted (regardless of the order of treatment) - Treated with at least one of KGFR-TKIs (regardless of treatment with or without systemic chemotherapies) - In case the patient previously received any of the treatments including systemic chemotherapy, radiation therapy, surgery, and hormonal therapy, there should be at least 2 weeks of time interval between the last day of the previous treatment and the start of TAGRISSO™, and the remaining toxicity should be ≤ CTCAE grade 1 at the time of starting study treatment (except alopecia and grade 2, prior platinum-therapy related neuropathy) 4. ECOG performance status 0-2 5. Patients in whom T790 mutations are detected in at least one of the samples including tumor tissues, BALF (cell-free DNA), plasma (cell-free DNA), and pleural effusion (cell-free DNA) 6. --- L858R --- --- L861Q ---

Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry Inclusion Criteria: 1. Age ≥ 20, and patients who understand information about the trial and voluntarily agree to participate in the trial 2. Histological or cytological confirmation diagnosis of NSCLC and inoperable stage IIIB or IV at the time of study enrolment 3. Patients with EGFR sensitizing mutation (E19Del, L858R, L861Q, G719X) positive, who had shown clinical benefits (responders (CR or PR) and SD ≥6 months) from EGFR-TKIs and had developed progressive disease following those therapy - Patients who have histories of previous exposure to EGFR-TKIs or other systemic chemotherapies are permitted (regardless of the order of treatment) - Treated with at least one of KGFR-TKIs (regardless of treatment with or without systemic chemotherapies) - In case the patient previously received any of the treatments including systemic chemotherapy, radiation therapy, surgery, and hormonal therapy, there should be at least 2 weeks of time interval between the last day of the previous treatment and the start of TAGRISSO™, and the remaining toxicity should be ≤ CTCAE grade 1 at the time of starting study treatment (except alopecia and grade 2, prior platinum-therapy related neuropathy) 4. ECOG performance status 0-2 5. Patients in whom T790 mutations are detected in at least one of the samples including tumor tissues, BALF (cell-free DNA), plasma (cell-free DNA), and pleural effusion (cell-free DNA) 6. --- L858R --- --- L861Q ---


3 T790M

Progression-free survival (PFS) the time from first dose of the study drug until the date of disease progression or death by any cause.. T790M postive rate in Plasma cell free DNA. --- T790M ---

T790M postive rate in BALF free DNA. --- T790M ---

T790M postive rate in tissue. --- T790M ---

Concordance rate of T790M positivity between plasma & BALF. --- T790M ---

T790M sensitivity & specificity in Plasma & BALF (gold standard: tissue biopsy). --- T790M ---

Patients must have a life expectancy ≥ 12 weeks Exclusion Criteria: 1. Patients who were previously treated with any of the drugs targeting T790M mutation such as AZD9291 (Osimertinib), HM61713 (Olmutinib), and CO-1686 (Rociletinib) 2. Patients currently receiving medications known to be potent inhibitors of CYP3A4 and potent inducers of CYP3A4 (at least 1week prior study enrolment) 3. Patients who have preexisting or coexisting malignancies in other parts except for effectively treated non-melanoma skin cancer, CIS cervical cancer, DCIS breast cancer, thyroid cancer or malignancies that were effectively treated, have maintained at least 3 years of remission state and can be regarded as completely cured 4. Patients who have severe or unstable medical conditions such as prior or current clinically significant cardiovascular abnormality in accordance with the investigator's judgment such as uncontrolled hypertension, heart failure (NYHA classification ≥3), unstable angina or uncontrolled arrhythmia, and acute myocardial infarction within 6 months before study enrolment corrected QTcB >450msec in 12 lead EKG 5. Patients with current or prior interstitial lung disease 6. Patients with current or prior uncontrolled gastrointestinal diseases (e.g., crohn's disease, ulcerative colitis, chronic diarrhea, malabsorption) that would preclude adequate absorption of IP. 7. Patients with active hepatitis B (identified by the presence of HBsAg and/or HBV DNA), active hepatitis C (identified by the presence of HCV RNA), and known human immunodeficiency virus (HIV) 8. Patients with histories of hypersensitivity to IP or any components of the agent 9. Patients with any of the following genetic predispositions including galactose intolerance, lactose intolerance, or glucose-galactose malabsorption 10. --- T790M ---



HPO Nodes


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