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Sponsors and Collaborators: |
National Taiwan University Hospital National Cheng-Kung University Hospital Taipei Veterans General Hospital,Taiwan |
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Information provided by: | National Taiwan University Hospital |
ClinicalTrials.gov Identifier: | NCT00632268 |
The primary end-point of this study is to evaluate the objective response rates, and the secondary end-points are overall survival, progression-free survival and safety profile of low-dose RAD001 (everolimus) plus cisplatin and HDFL (weekly 24-hour infusion of high-dose 5-FU and leucovorin) chemotherapy in the first-line treatment for patients with unresectable, recurrent, or metastatic gastric cancer.
Condition | Intervention | Phase |
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Advanced Gastric Cancer |
Drug: RAD001; Cisplatin; 5-FU; Leucovorin |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Open Label, Single Group Assignment |
Official Title: | Phase II Study of Low-Dose RAD001(Everolimus) Plus Cisplatin and HDFL (Weekly 24-Hour Infusion of High-Dose 5-Fluorouracil and Leucovorin) Chemotherapy for First-Line Treatment of Unresectable, Recurrent or Metastatic Gastric Cancer |
Estimated Enrollment: | 41 |
Study Start Date: | February 2008 |
Estimated Study Completion Date: | March 2010 |
Estimated Primary Completion Date: | March 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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A: Experimental
Drug:RAD001 Drug:Cisplatin Drug:5-FU
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Drug: RAD001; Cisplatin; 5-FU; Leucovorin
RAD001: oral 10mg/day on Day 1,8,15 Cisplatin:infusion 35mg/m2/day on Day 1,8 5-FU:infusion 2000mg/m2/day on Day 1,8,15
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Non-resectable gastric cancer is an incurable disease, with a median survival of 4 months if untreated. Systemic chemotherapy confers prolongation of survival and improvement of quality of life. Regimens containing cisplatin and 5-fluorouracil (5-FU) are widely adopted in the world. The overall response rate and median overall survival of the P-HDFL regimen (cisplatin and weekly 24-hour infusion of high-dose 5-FU and leucovorin) for advanced gastric cancer are 60% (45%-76%, 95% C.I.) and 10 months, respectively. This regimen (P-HDFL) is very popular in Taiwan because of high objective response rates and low treatment-related toxicities. Adding a third active chemotherapeutic agent to cisplatin and 5-FU doublet does not seem to improve efficacy. Further, most of the patients with recurrent or metastatic gastric cancer are frequently associated with a poor general condition which prohibits intensive chemotherapy. Therefore, combination of P-HDFL with biologic agents(such as everolimus, etc.)is an attractive alternative. PI3K/Akt/mTOR pathway is actively participating in cell proliferation and survival of human gastric cancers. We have recently demonstrated that RAD001(everolimus),an mTOR inhibitor, although with only modest growth inhibitory effects as a single agent, has significant synergistic cytotoxicity with cisplatin and 5-FU in gastric cancer cells. The concentration of RAD001 needed for synergism with cisplatin and 5-FU is as low as 0.5 to 5 nM. And, as expected, RAD001 has significant inhibition of downstream molecules such as 4E-BP1 and S6Kinase, in human gastric cancer cells. It is therefore reasonable to conduct a phase II study to examine if the combination of a relatively low dose of RAD001 and P-HDFL may improve the outcome of advanced gastric cancer.
This is an open-label, multi-center, phase II trial using low-dose RAD001 (10 mg po on D1,D8,&D15) plus P-HDFL chemotherapy (cisplatin 35 mg/m2 ivd 24 hrs on D1 & D8; 5-FU 2,000 mg/m2 and leucovorin 300 mg/m2 ivd 24 hrs on D1,D8,&D15) in chemotherapy-naïve patients with unresectable locally advanced, recurrent or metastatic gastric cancer. The treatment will be repeated every 28 days. The primary end-point is objective response rates evaluated by RECIST criteria, and the secondary end-points are overall survival, progression-free survival and safety profile. Approximately 41 patients will be enrolled in order to obtain the 37 evaluable patients required by Simon two-stage minimax design. All enrolled patients will be subjected to toxicity evaluations, but optionally to the correlative translational study of biomarkers in peripheral blood mononuclear cells. Patients with massive malignant ascites will optionally participate the study of biomarkers in neoplastic cells in ascites.
Ages Eligible for Study: | up to 75 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Kun-Huei Yeh, M.D.,Ph.D. | 886-2-2312-3456 ext 67514 | khyeh@ntu.edu.tw |
Taiwan | |
Department of Oncology, National Taiwan University Hospital | Recruiting |
Taipei, Taiwan, 100 | |
Contact: Kun-Huei Yeh, M.D.,Ph.D. 886-2-2312-3456 ext 67514 | |
Principal Investigator: Kun-Huei Yeh, M.D.,Ph.D. |
Principal Investigator: | Kun-Huei Yeh, M.D.,Ph.D. | Department of Oncology, National Taiwan University Hospital |
Responsible Party: | National Taiwan University Hospital ( Kun-Huei Yeh ) |
Study ID Numbers: | 200612015M |
Study First Received: | March 3, 2008 |
Last Updated: | May 17, 2009 |
ClinicalTrials.gov Identifier: | NCT00632268 History of Changes |
Health Authority: | Taiwan: Department of Health |
mTOR inhibitor RAD001 everolimus |
chemotherapy cisplatin high-dose 5-FU |
Everolimus Vitamin B Complex Digestive System Neoplasms Immunologic Factors Gastrointestinal Diseases Leucovorin Trace Elements Folinic Acid Immunosuppressive Agents Recurrence |
Digestive System Diseases Stomach Diseases Cisplatin Radiation-Sensitizing Agents Vitamins Stomach Neoplasms Fluorouracil Gastrointestinal Neoplasms Micronutrients Stomach Cancer |
Everolimus Vitamin B Complex Digestive System Neoplasms Immunologic Factors Gastrointestinal Diseases Antineoplastic Agents Growth Substances Physiological Effects of Drugs Leucovorin Immunosuppressive Agents Pharmacologic Actions |
Neoplasms Neoplasms by Site Digestive System Diseases Stomach Diseases Radiation-Sensitizing Agents Cisplatin Vitamins Stomach Neoplasms Therapeutic Uses Gastrointestinal Neoplasms Micronutrients |