Clinical trial NCT03588533: Herzuma-capecitabine/Cisplatin for Gastric Cancer
Official title: Safety and Efficacy Evaluation of Capecitabine, Cisplatin, and Herzuma Combination Chemotherapy for the First Line Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Patients.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: HER-2 Positive Gastric Cancer
Metastatic Cancer
Keywords: HER-2 Positive
Gastric or gastroesophageal adenocarcinoma
Herzuma
Lead sponsor: Dong-A University Hospital
Sponsor class: OTHER
Collaborators: name: Celltrion
First posted: 2018-07-17
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: * Herzuma 8mg/kg loading over 90min (1st cycle)
* Herzuma 6mg/kg maintenance over 30min (2nd cycle\~ ) every 3 weeks
* Capecitabine 1000mg/m2 p.o. bid D1-D14 every 3 weeks
* Cisplatin 60\~100mg/m2 i.v. D1 every 3 weeks
Primary purpose: TREATMENT

Brief summary: Stomach cancer is the fifth largest cancer in the world. Despite many combinations of studies, metastatic stomach cancer shows a median survival period of 10 to 12 months.

According to a report in Korea in 2010, 17 % of cancer patients had over-expression of human epidemiology growth factor receptor 2 (HER-2). And Using of Trastuzumab reported better results.Herzuma® is the Trastuzumab biosimilar (Biosimilar) cloned antibody.

In this study, the investigators want to prospectively analyze the effects and side effects of Herzuma® in gastric or gastroesophageal adenocarcinoma.

Detailed description: Stomach cancer is the fifth largest cancer in the world, with an estimated 723,000 patients each year, and cancer-related deaths being the third leading cause. In contrast to the decline in the West, the Far East Asia, including South Korea, showed a high prevalence of cancer. In 2014, 29,854 new cases of cancer were reported in Korea. This is the second most important cancer in terms of incidence and the third in cancer related mortality.

The 5 year survival rate has increased to 74 % due to increased early detection of stomach cancer, but in the case of metastatic stomach cancer, the rate of gastric cancer is about one-third of the total number of stomach cancer cases, resulting in poor outcomes. Treatment is 5-fluorouracil, Oxaliplatin, Irinotecan, Epirubicin , Docetaxel, etc. based on platinum or non-platinum. Despite many combinations of studies, metastatic stomach cancer shows a median survival period of 10 to 12 months..

According to a report in Korea in 2010, 17 % of cancer patients had over-expression of human epidemiology growth factor receptor-2(HER-2). And Using of Trastuzumab reported better results in progression free survival (18.6 months vs. 17.1 months) and total overall survival (13.8 months vs. 11.1 months) (hazard ratio 0.74 ; 95 % confidential interval(CI) 0.60-0.91 ; p=0.0046) Trastuzumab was first used for HER-2 and breast cancer, and in three weeks of treatment, it is recommended to perform an induction phase of 8 mg/kg of 90 min and then a maintenance phase of 6mg/kg of 30min to 60min infusion. However, clinical research and data analysis are required because of concerns of toxic expression due to short-term injection. The phase I study of the maintenance 30 minutes toxicity was performed in breast cancer, and there was little difference from 60 minutes of injection in a 250ml or 100ml solution or new toxic event.

Herzuma® is the Trastuzumab biosimilar (Biosimilar) cloned antibody. In the phase I pharmacodynamics study, same the results with trastuzumab were reported. Biosimilar use was approved based on the results of a phase III clinical study on breast cancer. A double-blind, random assignment test was conducted on 549 HER-2 positive breast cancer patients comparing the validity and stability of Trastuzumab. The primary goal was to achieve a postoperative pathologic complete remission in 46.8 % of Herzuma® compared to 50.4% of trastuzumab. In addition, the secondary goal of "overall response rate " and "pharmacodynamics" showed the same results as the Trastuzumab control group.

Biosimilar Herzuma® licensed through breast cancer study also can be used in HER-2 overexpressed stomach cancer. However, there has not been a study on the effects and side effects of the drug.

So in this study, the investigators want to prospectively analyze the effects and side effects of Herzuma® in gastric or gastroesophageal adenocarcinoma.

Eligibility criteria: Inclusion Criteria:

1. Gastric or gastroesophageal junction adenocarcinoma
2. HER-2 immuno-histochemical (IHC) (3 +) stain or her-2 silver in situ hybridization(SISH)/fluorescence in situ hybridization(FISH) (+)
3. Herzuma® -capecitabine/cisplatin combination regimen is planned as a first line treatment

Exclusion Criteria:

1. Other type of cancer of Gastric or gastroesophageal junction adenocarcinoma (e.g., lymphoma, sarcoma)
2. HER-2 (0/1+) in IHC or her-2 SISH/FISH (-).
3. Patients who previously performed stomach cancer treatment as a palliative setting.

Primary outcomes:
measure: Adverse event
timeFrame: up to 12 months
Secondary outcomes:
measure: Overall response rate
timeFrame: up to 6 months
measure: Progression free survivals (PFS)
timeFrame: up to 12 months
measure: All adverse events
timeFrame: up to 12 months
measure: Overall survivals (OS)
timeFrame: up to 12 months
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
Study officials:
affiliation: Dong-A University Hospital
name: Sung Yong Oh, MD
role: PRINCIPAL_INVESTIGATOR
References: