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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2008 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01079702
First received: March 2, 2010
Last updated: NA
Last verified: January 2008
History: No changes posted
  Purpose

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 Intervention Phase
Advanced Malignancies
Drug: Everolimus
Drug: Capecitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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:
  • Time to treatment failure [ Time Frame: Every 3 months during the first 2 years, and every 6 months thereafter. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 35
Study Start Date: April 2008
Estimated Study Completion Date: January 2011
Estimated Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
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
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
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         
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   
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)
  More Information

No publications provided

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
Study First Received: March 2, 2010
Last Updated: March 2, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

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

ClinicalTrials.gov processed this record on August 18, 2014