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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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Advanced Malignancies

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Description:

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.

Outcome 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

Safety Issue:

Yes

Principal Investigator

Hanneke Wilmink, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Authority:

Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Study ID:

AMCmedonc08/010

NCT ID:

NCT01079702

Start Date:

April 2008

Completion Date:

January 2011

Related Keywords:

  • Advanced Malignancies
  • Neoplasms

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