A Phase I-II Study of HM781-36B Combined With Paclitaxel and Trastuzumab in HER-2 Positive Advanced Gastric Cancer

Study Overview
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Brief Summary
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[Phase I] The main objective of this study is to evaluate the safety, tolerability and determine the Recommended Dose (RD) of HM781-36B(Poziotinib)combined with Paclitaxel and Trastuzumab [Phase II] The main objective of this study is to evaluate anticancer activity through determination of response rate of HM781-36B(Poziotinib)combined with Paclitaxel and Trastuzumab in patients with HER-2 positive advanced gastric cancer

Detailed Description
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Besides the main objectives, there are other objectives as follows: [Phase I] To assess the pharmacokinetic profile of HM781-36B(Poziotinib) combined with Paclitaxel and Trastuzumab To evaluate anticancer activity of HM781-36B(Poziotinib) combined with Paclitaxel and Trastuzumab in patients with HER-2 positive advanced gastric cancer To evaluate PFS(Progression-Free Survival), TTP (Time To Tumor Progression), and DOR (Duration of Overall Response) [Phase II] To assess the safety, tolerability of HM781-36B(Poziotinib) combined with Paclitaxel and Trastuzumab To evaluate tumor response through determination of disease control rate , PFS(Progression-Free Survival), TTP (Time To Tumor Progression), and DOR (Duration of Overall Response)

Official Title
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A Phase I-II Study to Assess the Safety, Efficacy and Pharmacokinetic Profile of HM781-36B Combined With Paclitaxel and Trastuzumab in Patients With HER-2 Positive Advanced Gastric Cancer

Conditions
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HER-2 Positive Advanced Gastric Cancer

Intervention / Treatment
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* Drug: HM781-36B(Poziotinib)
* Drug: Paclitaxel
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed advanced gastric cancer including gastroesophageal junction adenocarcinoma At least one measurable lesion defined by RECIST(v1.1) FISH+ or IHC3+ (regardless of FISH results) Age≥19 ECOG ≤ 2 Life expectancy ≥ 12 weeks Adequate bone marrow and no abnormal heart and lung function No radiotherapy, other anticancer drugs or immunotherapy is allowed during this study Subjects must provide written informed consent prior to performance of study specific procedures or assessments, and must be willing to comply with treatment and follow up assessments and procedures Exclusion Criteria: Patients with a history of hypersensitivity to Trastuzumab and who have been treated with medicine including Cremophor EL Patients who have a current active malignancy other than gastric adenocarcinoma (with exception of non-melanoma skin cancer or cervical cancer in situ) Patients who have previously received taxane-based chemotherapy The presence of central nervous system metastases Patients who have a blood tumor such as leukemia, or who had previously received, or are planning to receive, the bone marrow transplant Patients with uncontrolled infection Patients who have GI malabsorption or difficulty taking oral medication Patients with following diseases are excluded: Patients with psychiatric or congenital disorder which can affect adherence or make hard to follow the requirements of the protocol Pregnant or breastfeeding women or women of childbearing who do not use an appropriate method of contraception (male patient should also use an appropriate method of contraception)

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HM781-36B, Paclitaxel, Trastuzumab<br>HM781-36B(Poziotinib): QD*2weeks/3weeks Paclitaxel: 175mg/m2 Trastuzumab(Herceptin): 8mg/kg | Drug: HM781-36B(Poziotinib)<br>* QD*2weeks/3weeks<br>* Other names: Poziotinib;Drug: Paclitaxel<br>* 175mg/m2<br>Drug: Trastuzumab<br>* 8mg/kg<br>* Other names: Herceptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety evaluation(phase I) | Dose limiting toxicity (DLT), Maximum tolerance dose (MTD) | DLT will be evaluated on Day 21 during cycle 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy evaluation(Phase II) | Efficacy evaluation; phase II (Simon's two-stage minimax design): Disease Control Rate (CR, PR, SD), PFS(Progression-Free Survival), TTP (Time To Tumor Progression), and DOR (Duration of Overall Response) | Efficacy will be evaluated every 6 weeks or 9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HM781-36B, Paclitaxel, Trastuzumab