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

Phase 1

Completed

• Conditions: HER-2 Positive Advanced Gastric Cancer
• Interventions: Drug: HM781-36B(Poziotinib); Drug: Paclitaxel; Drug: Trastuzumab

• Registration Number: NCT01746771
• Lead Sponsor: Hanmi Pharmaceutical Company Limited

Brief Summary

\[Phase I\] 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

Besides the main objectives, there are other objectives as follows:

\[Phase I\]

1. To assess the pharmacokinetic profile of HM781-36B(Poziotinib) combined with Paclitaxel and Trastuzumab

2. To evaluate anticancer activity of HM781-36B(Poziotinib) combined with Paclitaxel and Trastuzumab in patients with HER-2 positive advanced gastric cancer

3. To evaluate PFS(Progression-Free Survival), TTP (Time To Tumor Progression), and DOR (Duration of Overall Response)

\[Phase II\]

1. To assess the safety, tolerability of HM781-36B(Poziotinib) combined with Paclitaxel and Trastuzumab

2. 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)

Study Timeline

• Study Start: 2012-11
• Study First Submitted: 2012-12-03
• Study First Submitted QC: 2012-12-09
• Study First Posted: 2012-12-11
• Primary Completion: 2015-08
• Study Completion: 2015-08
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-01
• Last Update Posted: 2016-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

1. Histologically or cytologically confirmed advanced gastric cancer including gastroesophageal junction adenocarcinoma
2. At least one measurable lesion defined by RECIST(v1.1)
3. FISH+ or IHC3+ (regardless of FISH results)
4. Age≥19
5. ECOG ≤ 2
6. Life expectancy ≥ 12 weeks
7. Adequate bone marrow and no abnormal heart and lung function
8. No radiotherapy, other anticancer drugs or immunotherapy is allowed during this study
9. 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

1. Patients with a history of hypersensitivity to Trastuzumab and who have been treated with medicine including Cremophor EL
2. Patients who have a current active malignancy other than gastric adenocarcinoma (with exception of non-melanoma skin cancer or cervical cancer in situ)
3. Patients who have previously received taxane-based chemotherapy
4. The presence of central nervous system metastases
5. Patients who have a blood tumor such as leukemia, or who had previously received, or are planning to receive, the bone marrow transplant
6. Patients with uncontrolled infection
7. Patients who have GI malabsorption or difficulty taking oral medication
8. Patients with following diseases are excluded:
9. Patients with psychiatric or congenital disorder which can affect adherence or make hard to follow the requirements of the protocol
10. 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HM781-36B, Paclitaxel, Trastuzumab	HM781-36B(Poziotinib)	HM781-36B(Poziotinib): QD\*2weeks/3weeks Paclitaxel: 175mg/m2 Trastuzumab(Herceptin): 8mg/kg
HM781-36B, Paclitaxel, Trastuzumab	Trastuzumab	HM781-36B(Poziotinib): QD\*2weeks/3weeks Paclitaxel: 175mg/m2 Trastuzumab(Herceptin): 8mg/kg
HM781-36B, Paclitaxel, Trastuzumab	Paclitaxel	HM781-36B(Poziotinib): QD\*2weeks/3weeks Paclitaxel: 175mg/m2 Trastuzumab(Herceptin): 8mg/kg

Primary Outcome Measures

Name	Time	Method
Safety evaluation(phase I)	DLT will be evaluated on Day 21 during cycle 1	Dose limiting toxicity (DLT), Maximum tolerance dose (MTD)

Secondary Outcome Measures

Name	Time	Method
Efficacy evaluation(Phase II)	Efficacy will be evaluated every 6 weeks or 9 weeks	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)

Trial Locations

Locations (1)

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of