A Phase II Study to Assess Efficacy of Combined Treatment With Erlotinib (Tarceva) and Silybin-phytosome (Siliphos) in Patients With EGFR Mutant Lung Adenocarcinoma

Sponsor

MedicalLogic (Industry)

Overall Status

Unknown status

CT.gov ID

NCT02146118

Collaborator

Kosin University Gospel Hospital (Other)

Enrollment

Location

Arm

Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Title and stage of study A Phase II Study to Assess Efficacy of Combined Treatment with Erlotinib (Tarceva) and Silybin-phytosome (Siliphos) in Patients with EGFR mutant lung adenocarcinoma
Endpoints Primary Endpoint : tumour response rate Secondary Endpoint : progression-free survival, overall survival, and safety assessment
Study Rationale Even though it is commonly accepted that EGFR TKIs are effective to EGFR mutation positive lung cancer patients, still remains its resistance issue.

The Silybin which is extract from mugwort bean Thistle and used for hepatoprotective drug for a long time with very low adverse events in Eastern countries. Recently, there are some reports regarding its anti-cancer effects through several preclinical studies.

The safety of Siliphos which is developed agent from silybin for improving intestinal absorption was demonstrated in PhaseⅠtrial.

Recently investigators found out Silybin is effective for blocking EGFR signal in different mechanism from Erlotinib and it can be expected additional impact with combination therapy with preclinical data.

Our research team can expect to improve Lung cancer treatment if the combination therapy (Silybin_Erlotinib) improves patients' response and Overall survivor.

Treatment method Erlotinib (Tarceva 150 mg/day) and Silybin (Siliphos 1g bid/day) q 4 weeks
Assessment criteria For toxicity assessment, posttreatment recurrence and survival rates will be investigated based on NCI-CTCAE ver 4.0 and RTOG. Efficacy assessment will be conducted through measurement of lesions by CT and RECIST criteria. Overall survival (OS), progression-free survival (PFS), and time to tumour progression (TTP) will be estimated using a Kaplan-Meier analysis. In addition, effect of pre-treatment T790M on response and PFS will be analyzed.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Erlotinib Dietary Supplement: Silybin-phytosome	Phase 2

Detailed Description

Title and stage of study

A Phase II Study to Assess Efficacy of Combined Treatment with Erlotinib (Tarceva) and Silybin-phytosome (Siliphos) in Patients with EGFR mutant lung adenocarcinoma

Endpoints

Primary Endpoint : tumour response rate Secondary Endpoint : progression-free survival, overall survival, and safety assessment

Inclusion/exclusion criteria

Inclusion criteria

Histological or cytologic diagnosis of stage IV lung adenocarcinoma and confirmed EGFR mutation
Patients who have not received chemotherapy before. However, patients who received postoperative adjuvant chemotherapy more than 6 months ago are eligible.
Patients with a lesion that can be measured a response-evaluation according to the RECIST criteria (at least one evaluable lesion)
Patients aged 20 years or older
ECOG performance status score of 0, 1 or 2
Expected lifetime of ≥3 months
Adequate bone marrow and liver functions maintained
Neutrophil count: > 1,500/㎕
Platelet count: > 100,000/㎕
Hb: > 9.0g/dL
AST/ALT: < 2.0 x upper normal limit
Bilirubin: < 1.25 x upper normal limit
Patients or their legally acceptable representatives must complete a written consent before initiation of the study and patients can comply with requirements for the study

Exclusion criteria

Symptomatic central nervous system (CNS) malignant tumor or metastasis. However, the patients who are treated for CNS metastasis can be enrolled if their disease is radiologically stable and asymptomatic. Asymptomatic patients without a history of CNS metastasis do not need screening.
Evidence of severe or uncontrolled systemic diseases at the investigator's discretion (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal diseases)
Patients who have been treated with EGFR inhibitors before
Patients treated with other investigational products or unapproved drugs within 28 days before enrollment in this study
Pregnant and lactating women, and patients of childbearing who do not agree to use contraception
Patients ineligible for the study at the investigator's discretion
Study Rationale

Even though it is commonly accepted that EGFR TKIs are effective to EGFR mutation positive lung cancer patients, still remains its resistance issue.

The safety of Siliphos which is developed agent from silybin for improving intestinal absorption was demonstrated in PhaseⅠtrial.

Our research team can expect to improve Lung cancer treatment if the combination therapy (Silybin_Erlotinib) improves patients' response and Overall survivor.

Treatment method

Erlotinib (Tarceva 150 mg/day) and Silybin (Siliphos 1g bid/day) q 4 weeks

Assessment criteria

For toxicity assessment, posttreatment recurrence and survival rates will be investigated based on NCI-CTCAE ver 4.0 and RTOG. Efficacy assessment will be conducted through measurement of lesions by CT and RECIST criteria. Overall survival (OS), progression-free survival (PFS), and time to tumour progression (TTP) will be estimated using a Kaplan-Meier analysis. In addition, effect of pre-treatment T790M on response and PFS will be analyzed.

Statistical method Object response rate (ORR) will be reported with its 2-sided 95% confidence interval. If the evaluable number of subject is 42 and number of response is 25 or more, this study certainly imply that this treatment has an efficacy worthy of further investigation, perhaps in a Phase III randomized trial.

Progression Free Survival (PFS) is defined as the time from beginning of treatment until object disease progression as defined by RECIST or death. Patient who have not progressed or died at the time of the statistical analysis will be censored at the time of their last evaluable RECIST assessment. Kaplan-Meier plots of PFS and estimated of median PFS will be presented.

Overall survival (OS) is defined as the time from beginning of treatment until death by any cause. Patient who have not died at the time of the data cut-off, or are lost to follow up will be censored at the time they were last known to be alive. Kaplan-Meier plots of OS and estimated of median PFS will be presented.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study to Assess Efficacy of Combined Treatment With Erlotinib (Tarceva) and Silybin-phytosome (Siliphos) in Patients With EGFR(Epidermal Growth Factor Receptor) Mutant Lung Adenocarcinoma

Study Start Date :

Apr 1, 2014

Anticipated Primary Completion Date :

Sep 1, 2015

Anticipated Study Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Erlotinib and Silibin	Drug: Erlotinib Erlotinib 150 mg/day q 4 weeks Other Names: Tarceva Dietary Supplement: Silybin-phytosome Silybin-phytosome 1g bid/day q 4 weeks Other Names: Siliphos

Arm

Intervention/Treatment

Experimental: Erlotinib and Silibin

Drug: Erlotinib

Erlotinib 150 mg/day q 4 weeks

Other Names:

Tarceva

Dietary Supplement: Silybin-phytosome

Silybin-phytosome 1g bid/day q 4 weeks

Other Names:

Siliphos

Outcome Measures

Primary Outcome Measures

Tumour response rate [12 months]
Efficacy assessment will be conducted through measurement of lesions by CT and RECIST criteria.

Secondary Outcome Measures

Safety assessment [12 months]
For toxicity assessment, posttreatment recurrence and survival rates will be investigated based on NCI-CTCAE ver 4.0 and RTOG.

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. Histological or cytologic diagnosis of stage IV lung adenocarcinoma and confirmed EGFR mutation
1. Patients who have not received chemotherapy before. However, patients who received postoperative adjuvant chemotherapy more than 6 months ago are eligible.
1. Patients with a lesion that can be measured a response-evaluation according to the RECIST criteria (at least one evaluable lesion)
1. Patients aged 20 years or older
1. ECOG performance status score of 0, 1 or 2
1. Expected lifetime of ≥3 months
1. Adequate bone marrow and liver functions maintained

Neutrophil count: > 1,500/㎕
Platelet count: > 100,000/㎕
Hb: > 9.0g/dL
AST/ALT: < 2.0 x upper normal limit
Bilirubin: < 1.25 x upper normal limit

1. Patients or their legally acceptable representatives must complete a written consent before initiation of the study and patients can comply with requirements for the study

Exclusion Criteria:

1. Symptomatic central nervous system (CNS) malignant tumour or metastasis. However, the patients who are treated for CNS metastasis can be enrolled if their disease is radiologically stable and asymptomatic. Asymptomatic patients without a history of CNS metastasis do not need screening.
1. Evidence of severe or uncontrolled systemic diseases at the investigator's discretion (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal diseases)
1. Patients who have been treated with EGFR inhibitors before
1. Patients treated with other investigational products or unapproved drugs within 28 days before enrollment in this study
1. Pregnant and lactating women, and patients of childbearing who do not agree to use contraception
1. Patients ineligible for the study at the investigator's discretion