A Study of Trastuzumab in Combination With TS-ONE & Cisplatin in First-line Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer
|Gastric Cancer||Drug: Trastuzumab in Combination with TS-ONE and cisplatin||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of Trastuzumab in Combination With TS-ONE and Cisplatin in First-line Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer.|
- Overall Response Rate (ORR) [ Time Frame: Fom the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented ]
- Progression free survival (PFS) [ Time Frame: Time from registration until objective tumor progression or death for any reason that occurs by the end of the study. ]
- Overall survival (OS) [ Time Frame: Time from registration to the date of death. ]
- Time to Treatment Failure (TTF) [ Time Frame: Time from registration until discontinuation of treatment for any reason (including progression of disease, treatment toxicity, and death). ]
- Clinical Benefit Rate (CBR) [ Time Frame: proportion of patients with confirmed CR, PR, and SD over 24 weeks. ]
- Duration of Response (DR) [ Time Frame: Time from first assessment of CR or PR until the first date of PD or death within 60 days of the last tumor assessment or registration, whichever is first. ]Median time will be estimated using the Kaplan Meier method. 95% confidence interval of the median time will be estimated.
- Safety Evaluations [ Time Frame: Focus on AEs and laboratory assessments. ]
AEs will be coded according to the Medical Dictionary for Regulatory Activities Terminology (MedDRA) and the severity of the toxicities will be graded according to the NCI CTCAE criteria, version 3.0, where applicable. Concomitant medications will be coded according to WHO Medication Dictionary for Concomitant Medication.
All AEs will be summarized (incidence) and listed by the System Organ Class (SOC), preferred term, toxicity/severity grade, and causal relationship. In addition, separate summaries of SAEs and Grade 3 or 4 AEs will be presented. Cardiac AEs including asymptomatic LVEF drops will also be summarized in separate tables.
Hematological and chemistry laboratory parameters will be graded according to the NCI CTCAE criteria, where applicable. Absolute values and changes from baseline will be summarized by cycle. In addition, worst severity grade will also be summarized.
|Study Start Date:||February 2011|
|Estimated Study Completion Date:||December 2016|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Trastuzumab in Combination with TS-ONE and cisplatin
The initial dose of cisplatin is fixed to be 60 mg/m2 and intravenously administered over 1 hour on day 1 of the cycle. TS-ONE is orally administered consecutive 14-day followed by 7-day rest. The initial standard dose of TS-ONE is determined based on the body surface area tabled below. Trastuzumab is intravenously administered with the loading dose of 8 mg/kg followed by maintenance dose of 6mg/kg in day 1 of each cycle. The study treatments are repeated every 3 weeks. Study treatment can continue until PD, but cisplatin can be skipped or discontinued if patients experienced unbearable toxicity which comes from cisplatin.
Drug: Trastuzumab in Combination with TS-ONE and cisplatin
Subjects will receive treatment that combined TS-ONE, cisplatin and trastuzumab every 3 weeks in this study. This 3 weeks period of time is called a cycle. The cycle will be repeated until subject experience disease progression or unbearable toxicities or they choose to withdraw from the study. Each cycle is numbered in order.
Gastric carcinoma is the second most common cause of cancer death world-wide. Approximately 875,000 patients are diagnosed world-wide with gastric cancer each year. Gastric cancer is often diagnosed at an advanced stage1. At diagnosis, while some patients have gastric carcinoma that extends within loco-regional confines and can undergo a curative resection, many patients cannot undergo curative resection. Gastric cancer continues to pose a major medical challenge.
While advanced gastric carcinoma is incurable, chemotherapy can have a palliative effect in symptomatic patients. Chemotherapy improves outcome compared to best supportive care in gastric cancer. Various chemotherapeutic agents including 5-FU, mitomycin, etoposide, cisplatin, irinotecan and the taxanes, have demonstrated activity as monotherapy. Combination chemotherapy has been shown to have better survival outcomes than single agent chemotherapy Standard chemotherapy for advanced gastric carcinoma includes a fluoropyrimidine and platinum -based combination chemotherapy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01228045
|National University Hospital|
|Principal Investigator:||Wei Peng Yong, MRCP, MB ChB||National University Hospital Singapore, NUHS|