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

May 20, 2014 updated by: Chang-gyu Choi, MedicalLogic

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

  1. 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
  2. Endpoints Primary Endpoint : tumour response rate Secondary Endpoint : progression-free survival, overall survival, and safety assessment

  3. 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.

  4. Treatment method Erlotinib (Tarceva 150 mg/day) and Silybin (Siliphos 1g bid/day) q 4 weeks
  5. 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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

  1. 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

  2. Endpoints

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

  3. Inclusion/exclusion criteria

    Inclusion criteria

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

    7. Adequate bone marrow and liver functions maintained

      1. Neutrophil count: > 1,500/㎕
      2. Platelet count: > 100,000/㎕
      3. Hb: > 9.0g/dL
      4. AST/ALT: < 2.0 x upper normal limit
      5. Bilirubin: < 1.25 x upper normal limit
    8. 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 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.
    2. Evidence of severe or uncontrolled systemic diseases at the investigator's discretion (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal diseases)
    3. Patients who have been treated with EGFR inhibitors before
    4. Patients treated with other investigational products or unapproved drugs within 28 days before enrollment in this study
    5. Pregnant and lactating women, and patients of childbearing who do not agree to use contraception
    6. Patients ineligible for the study at the investigator's discretion

  4. 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.

  5. Treatment method

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

  6. 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.

  7. 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 Type

Interventional

Enrollment (Anticipated)

42

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Korea, Republic of
      • Busan, Korea, Republic of, 602-702
        • Recruiting
        • Gosin University Gospel Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

  • 7. Adequate bone marrow and liver functions maintained

    1. Neutrophil count: > 1,500/㎕
    2. Platelet count: > 100,000/㎕
    3. Hb: > 9.0g/dL
    4. AST/ALT: < 2.0 x upper normal limit
    5. Bilirubin: < 1.25 x upper normal limit
  • 8. 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.
  • 2. Evidence of severe or uncontrolled systemic diseases at the investigator's discretion (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal diseases)
  • 3. Patients who have been treated with EGFR inhibitors before
  • 4. Patients treated with other investigational products or unapproved drugs within 28 days before enrollment in this study
  • 5. Pregnant and lactating women, and patients of childbearing who do not agree to use contraception
  • 6. Patients ineligible for the study at the investigator's discretion

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumour response rate
Time Frame: 12 months
Efficacy assessment will be conducted through measurement of lesions by CT and RECIST criteria.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety assessment
Time Frame: 12 months
For toxicity assessment, posttreatment recurrence and survival rates will be investigated based on NCI-CTCAE ver 4.0 and RTOG.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MedicalLogic

Collaborators

Kosin University Gospel Hospital

Investigators

  • Study Director: Tae won Jang, Dr, Kosin University Gospel Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2014

Primary Completion (Anticipated)

September 1, 2015

Study Completion (Anticipated)

March 1, 2016

Study Registration Dates

First Submitted

May 7, 2014

First Submitted That Met QC Criteria

May 20, 2014

First Posted (Estimate)

May 23, 2014

Study Record Updates

Last Update Posted (Estimate)

May 23, 2014

Last Update Submitted That Met QC Criteria

May 20, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SLB-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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