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Everolimus and Capecitabine in Patients With Advanced Malignancy (m-TOR)

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ClinicalTrials.gov Identifier: NCT01079702
Recruitment Status : Unknown
Verified January 2008 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).
Recruitment status was:  Recruiting
First Posted : March 3, 2010
Last Update Posted : March 3, 2010
Sponsor:
Information provided by:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary:
In the investigators study the investigators combine everolimus, administrated twice daily at a fixed total dose of 10 mg continuously with capecitabine administered bid for 14 days followed by 7 days rest. In this study, capecitabine will be dose escalated.

Condition or disease Intervention/treatment Phase
Advanced Malignancies Drug: Everolimus Drug: Capecitabine Phase 1 Phase 2

Detailed Description:

The results form preclinical studies suggest that mTOR inhibitors are promising drugs for the treatment of various types of cancer. Everolimus seems the most attractive mTOR inhibitor because of the favourable pharmacokinetic profile and possibility of oral administration. Based on preclinical findings, mTOR inhibitors may be more efficacious when used in a rational combination with other cancer regiments like cytostatic drugs. Indeed, several multiagent combinations are being investigated in clinical trials at the moment, and the results are promising.

In our study we combine everolimus, administrated twice daily at a fixed total dose of 10 mg continuously with capecitabine administered bid for 14 days followed by 7 days rest. In this study, capecitabine will be dose escalated. The first dose level of capecitabine is 500 mg/m2 twice daily. Three patients will be enrolled per dose level, starting at dose level 1. If one of the 3 patients develops dose-limiting toxicity at any dose level, 3 other patients will start at the same dose level. If 2 or more out of these 6 patients develop DLT, no further dose escalations will be performed. The MTD will be considered to be the dose given at the previous lower level. No intrapatient dose escalation will be applied.

Once the MTD of capecitabine is established, the phase II part of the study will start in which 25 patients with various malignancies will be enrolled to evaluate the efficacy and feasibility of the combination of everolimus and capecitabine.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Non-randomized, Multi-center, Dose-escalating, Two-stage Efficacy and Feasibility Study of the Combination of Everolimus and Capecitabine in Patients With Advanced Malignancies
Study Start Date : April 2008
Estimated Primary Completion Date : April 2010
Estimated Study Completion Date : January 2011

Resource links provided by the National Library of Medicine



Intervention Details:
  • Drug: Everolimus
    Everolimus, administrated twice daily at a fixed total dose of 10 mg continuously.
    Other Name: Certican
  • Drug: Capecitabine
    Capecitabine administered bid for 14 days followed by 7 days rest. In this study, capecitabine will be dose escalated. The first dose level of capecitabine is 500 mg/m2 twice daily.
    Other Name: Xeloda


Primary Outcome Measures :
  1. Phase I part: Assessment of dose limiting toxicity and maximum tolerated dose. II part: efficacy and feasibility. Primary endpoint of the study will be response rate. [ Time Frame: During treatment: assessments on day 1 every cycle (3 weeks). After treatment: every 3 months during the first 2 years, and every 6 months thereafter ]
    Three patients will be enrolled per dose level, starting at dose level 1. If one of the 3 patients develops dose-limiting toxicity at any dose level, 3 other patients will start at the same dose level. If 2 or more out of these 6 patients develop DLT, no further dose escalations will be performed. The MTD will be considered to be the dose given at the previous lower level. No intrapatient dose escalation will be applied.


Secondary Outcome Measures :
  1. Time to treatment failure [ Time Frame: Every 3 months during the first 2 years, and every 6 months thereafter. ]
  2. Toxicity profile. [ Time Frame: During treatment: assessments on day 1 every cycle (3 weeks). After treatment: every 3 months during the first 2 years, and every 6 months thereafter. ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histological or cytological confirmed malignancies
  • Measurable lesion according to RECIST criteria (only for the phase II part of the study)
  • ECOG / WHO performance status of 0-2
  • Age ≥ 18 years
  • Life expectancy of at least 3 months
  • Minimal acceptable safety laboratory values defined as:
  • WBC ≥ 3.0 x 109 /L
  • Platelet count ≥ 100 x 109 /L
  • Hepatic function as defined by serum bilirubin ≤ 1.5 x ULN, ALT or AST ≤ 2.5 x ULN, in case of liver metastases ≤ 5 x ULN
  • Renal function as defined by creatinine < 150μmol/L
  • Able and willing to give written informed consent
  • Able to swallow and retain oral medication
  • Able and willing to undergo blood sampling for pharmacokinetic and pharmacogenetic analysis
  • Mentally, physically and geographically able to undergo treatment and follow up.

Exclusion Criteria:

  • Patients with known alcoholism, drug addiction and/or psychotic disorders in the history that are not suitable for adequate follow up
  • Women who are pregnant or breast feeding
  • Women of childbearing potential who refuse to use a reliable contraceptive method throughout the study
  • Serious concomitant systemic disorder that would compromise the safety of the patient, at the discretion of the investigator
  • Any other medical condition that would interfere with study procedures and/or decrease safety of the protocol treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01079702


Contacts
Contact: Hanneke Wilmink, MD, PhD +31 205665955 j.w.wilmink@amc.uva.nl
Contact: Dick Richel, MD, PhD +31 205665955 d.j.richel@amc.uva.nl

Locations
Netherlands
Academic Medical Center Recruiting
Amsterdam, Netherlands, 1105 AZ
Contact: Hanneke Wilmink, MD PhD    +31-20-5665955 ext 58919    j.w.wilmink@amc.uva.nl   
Contact: Lyda ter Hofstede    +31-20-5668229    trialmedonc@amc.uva.nl   
Academic Medical Center Recruiting
Amsterdam, Netherlands
Contact: Hanneke Wilmink, MD, PhD    +31 205665955    j.w.wilmink@amc.uva.nl   
Contact: Lyda ter Hofstede    +31 205668229    trialmedonc@amc.uva.nl   
Principal Investigator: Hanneke Wilmink, MD PhD         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Principal Investigator: Hanneke Wilmink, MD, PhD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Responsible Party: J.W.Wilmink, MD PhD, Academisch Medisch Centrum-Universiteit Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01079702     History of Changes
Other Study ID Numbers: AMCmedonc08/010
First Posted: March 3, 2010    Key Record Dates
Last Update Posted: March 3, 2010
Last Verified: January 2008

Additional relevant MeSH terms:
Neoplasms
Capecitabine
Everolimus
Sirolimus
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents