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CancerPhase 1NCT01096199

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

A Phase 1 study testing TS-ONE, Cisplatin, RAD001 in people with Cancer, run by National University Hospital, Singapore at 1 site in Singapore.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 21 to 80 years
Conditions the study is for
Cancer
What is being tested?
TS-ONE, Cisplatin, RAD001
How many people
35 participants
Where
1 siteSingapore
Study dates
Start not givento Sep 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically documented locally advanced, metastatic or recurrent solid malignancies that are refractory to standard therapy, for which convention therapy is not effective or platinum/fluoropyrimidine is indicated.
  • At least one measurable or evaluable disease defined by RECIST
  • Age >21 years old
  • Performance status (ECOG) 0-2
  • Life expectancy >3 months
  • No significant problems for oral intake and drug administration
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  • Adequate organ functions:
  • bone marrow function (ANC ≥ 1,500/uL, Platelet ≥ 100,000/ uL, Hb ≥ 9.0 g/dl)
  • renal function: serum creatinine ≤ UNL (if serum creatinine > ULN, creatinine clearance should be ≥ 60 mL/min)
  • hepatic function (Total bilirubin < 2 x UNL and AST/ALT levels < 3 x ULN without liver metastasis, total bilirubin < 3x ULN and AST/ALT levels < 5 x ULN with liver metastasis)
  • Prior systemic therapy (eg, cytotoxic chemotherapy or biologic therapy) and major surgery are allowed if at least 28 days has elapsed between completion of therapy and administration of study drugs
  • Ability to understand and willingness to sign a written informed consent before study entry

Who cannot join

  • Failure to recover from the reversible effects of previous chemotherapy, radiotherapy, hormonal, or biologic therapy prior to enrollment
  • Second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin or prior malignancy treated more than 5 years ago without recurrence)
  • Prior radiotherapy was administered to target lesions selected for this study, or radiotherapy to the non-target lesions has been completed within 4 weeks before randomization
  • Prior mTOR inhibitor
  • Presence of symptomatic or progressing CNS metastasis
  • Serious illness or medical conditions:
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  • Congestive heart failure (NYHA class III or IV), unstable angina or myocardial infarction within the past 12 months
  • Significant arrhythmias requiring medication and conduction abnormality such as over 2nd degree AV block
  • Uncontrolled hypertension
  • Hepatic cirrhosis (≥ Child class B)
  • Interstitial pneumonia
  • Psychiatric disorder that may interfere with protocol compliance
  • Unstable diabetes mellitus
  • Uncontrolled ascites or pleural effusion
  • Active infection
  • Receiving a concomitant treatment interacting with TS-1, cisplatin or RAD001. Flucytosine (a fluorinated pyrimidine antifungal agent) Antivirals such as sorivudine, ramivudine, brivudine or other chemically related agents, warfarin, phenprocoumon, phenytoin, allopurinol, immunosuppressive agents. Strong and moderate inhibitors or inducers of P-glycoprotein, CYP3A4 and CYP3A5 (appendix A) are not eligible; a minimal of 2 weeks wash- out period will be required after stop such medications
  • Known hypersensitivity to TS-1, CDDP or mTOR inhibitor.
  • Pregnant or lactating woman. Women of child bearing potential not using a contraceptive method
  • Sexually active fertile men not using effective birth control during medication of study drug and up to 6 months after completion of study drug if their partners are women of child-bearing potential
  • Any patients judged by the investigator to be unfit to participate in the study

Trial locations and contacts

1 site in 1 country.

Singapore1 site

  • National University Hospital

    Singapore, Singapore, 119074

Other trials in Singapore

About this study

Official title: A Phase I Study of TS-1, Cisplatin & RAD001 (Everolimus)

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
Cancer
Being tested
TS-ONE, Cisplatin, RAD001
Keywords
The purpose of the study is to evaluate the safety and feasibility of combining TS-1/CDDP with RAD001. Primary, Objectives, To determine the MTD/recommended phase II dose of TS-1/CDDP/RAD001 combination -To determine, the safety of TS-1/CDDP/RAD001 combination Secondary Objectives -To preliminarily describe any clinical activity in, platinum refractory disease, To assess to effect of concurrent TS-1/CDDP on RAD001 pharmacokinetics -To explore, the relationship of tumour biomarkers and treatment response
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TS-ONE, Cisplatin, RAD001Drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Mar 2010 (estimated)
  2. Primary completionSep 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Enrolment
35 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT01096199
Sponsor's protocol ID
PK02/12/09
Status last verified
Jan 2014
First submitted
29 Mar 2010
Last updated
22 Jan 2014
Results posted
No
Data monitoring committee
No

Publications

  • Liu LZ, Zhou XD, Qian G, Shi X, Fang J, Jiang BH. AKT1 amplification regulates cisplatin resistance in human lung cancer cells through the mammalian target of rapamycin/p70S6K1 pathway. Cancer Res. 2007 Jul 1;67(13):6325-32. doi: 10.1158/0008-5472.CAN-06-4261.

    PubMed 17616691

  • Lee S, Choi EJ, Jin C, Kim DH. Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA mRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line. Gynecol Oncol. 2005 Apr;97(1):26-34. doi: 10.1016/j.ygyno.2004.11.051.

    PubMed 15790433

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TS-ONE, Cisplatin, RAD001 in people with Cancer, run by National University Hospital, Singapore at 1 site in Singapore.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01096199, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2014.

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