Everolimus and Capecitabine in Patients With Advanced Malignancy

NCT ID: NCT01079702

Last Updated: 2010-03-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2011-01-31

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.

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.

Conditions

Advanced Malignancies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Everolimus

Everolimus, administrated twice daily at a fixed total dose of 10 mg continuously.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Certican; Xeloda

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: lead

Responsible Party

Academisch Medisch Centrum-Universiteit Amsterdam (AMC-UvA)

Principal Investigators

Hanneke Wilmink, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Academic Medical Center

Amsterdam, , Netherlands

Site Status: RECRUITING

Academic Medical Center

Amsterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Hanneke Wilmink, MD, PhD

Role: CONTACT

j.w.wilmink@amc.uva.nl

+31 205665955

Dick Richel, MD, PhD

Role: CONTACT

d.j.richel@amc.uva.nl

+31 205665955

Facility Contacts

Hanneke Wilmink, MD PhD

Role: primary

j.w.wilmink@amc.uva.nl

+31-20-5665955 ext. 58919

Lyda ter Hofstede

Role: backup

trialmedonc@amc.uva.nl

+31-20-5668229

Hanneke Wilmink, MD, PhD

Role: primary

j.w.wilmink@amc.uva.nl

+31 205665955

Lyda ter Hofstede

Role: backup

trialmedonc@amc.uva.nl

+31 205668229

Other Identifiers

AMCmedonc08/010

Identifier Type: -

Identifier Source: org_study_id