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A Study of TS-1, Cisplatin (CDDP) and RAD001 (Everolimus)

NCT01096199 · Status: TERMINATED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 35

Last updated 2014-01-22

No results posted yet for this study

Summary

Hypothesis: The addition of RAD001 to TS-1/CDDP is safe and can improved the efficacy of TS-1/CDDP. The rationale for combining RAD001 with TS-1/CDDP are:

1. Potential synergism for the combination TS-1/CDDP Activation of the PI3K/AKT/mTOR pathway is frequently a characteristic of worsening prognoses (through increased aggressiveness), resistance to treatment, extension of disease and progression. The antitumour effect of RAD001 is mediated through the antiproliferative and antiangiogenic activity of mTOR inhibition. In preclinical study, RAD001 demonstrated synergism with CDDP in several cancer types including lung (A549; CI 0.47), epidermoid cancer (KB-31; CI 0.74), colon cancer (HCT116; CI 0.47) and gastric cancer (SNU 1; CI 0.204, SNU 216; CI 0.546, SNU 638; CI 0.039, SNU 668; CI 0.396) (IB, Lee 2008 AACR).
2. Potential for overcoming TS-1/CDDP resistance. Upregulation of Akt pathway was found to be an important mechanism for acquired resistance to CDDP (Lee 2005 Gyn Onc, Liu 2007 Cancer Res). In addition, gastric cancers with upregulated Akt pathway are associate with primary resistance to 5- fluorouracil, adriamycin, mitomycin C, and cisplatin (Oki 2007 PASCO)
3. Overlapping antitumour activities with TS-1/CDDP RAD001 is effective and well tolerated against subcutaneous tumours established from a variety of tumour cell lines of diverse histotypes (NSCLC, pancreatic, gastric, colon, renal, melanoma, epidermoid), including a Pgp170-overexpressing, multi-drug resistant tumor line. Partial response to single agent RAD001 was seen in a patient with gastric cancer at the dose of 5mg/day and 2 patients (gastric and oesophageal cancer) at the dose of 10mg/day, in study C2101 and C1101 respectively. A clinical benefit (stable disease, partial response and complete response) was observed in 55% of patient with gastric cancer who had failed 1st line therapy (Yamada 2009 GCS ASCO). A phase III study of RAD001 in patients with 2nd/3rd line gastric cancer has currently opened for recruitment.

Conditions

Interventions

DRUG

TS-ONE, Cisplatin, RAD001

Sponsors & Collaborators

  • National University Hospital, Singapore

    lead OTHER

Principal Investigators

  • Wei Peng Yong, MRCP, MB ChB · National University Hospital, Singapore

Eligibility

Min Age
21 Years
Max Age
80 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Primary Completion
2012-09-30

Countries

  • Singapore

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01096199 on ClinicalTrials.gov