Informations générales (source: ClinicalTrials.gov)
EVESOR: a Phase 1 Trial of Everolimus and Sorafenib to Assess the Impact of Doses and Administration Sequences on Pharmacokinetic and Pharmacodynamic Effects of the Combination (EVESOR)
Interventional
Phase 1
Hospices Civils de Lyon (Voir sur ClinicalTrials)
avril 2013
octobre 2015
29 juin 2024
EVESOR multiparameter phase I trial aims at determining the safety of different doses and
dosing schedules of everolimus in combination with sorafenib as well as the recommended
doses & dosing schedules for phase 2 trials in adult patients with advanced solid tumors.
Etablissements
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| Hospices Civils de Lyon - 69002 - Lyon - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
- Patients with solid tumors (breast adenocarcinomas, colorectal adenocarcinomas,
renal cell carcinomas, gastric and oesophageal adenocarcinomas, pancreatic cancers,
hepatocellular carcinoma, ovarian and Fallopian tube adenocarcinomas, primary
peritoneal carcinoma, endometrial and cervix cancers, non-small cell lung carcinoma,
melanoma, thyroid carcinomas) resistant or not amenable to standard treatments
- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as
>20 mm with conventional techniques or as >10 mm with spiral CT scan.
- Patients must have assessable primary or metastatic lesion using dynamic contrast
enhanced ultrasound
- Patients must be willing to have two tumor biopsies performed (one before study
start and one during study treatment), unless medically contraindicated.
- No previous treatment with sorafenib and everolimus. Patients may have been
previously treated with one experimental drug: sorafenib or everolimus.
- No other limitation on prior therapy. However, there must be at least a 4 week
interval between initiation of study treatment and any prior radiotherapy or
systemic therapy, 6 weeks if the last regimen included BCNU or mitomycin C.
- Males and females aged >18 years.
- Life expectancy of greater than 12 weeks.
- ECOG performance status ≤ 2 (Karnofsky > 70%; see Appendix A).
- Patients must have normal organ and marrow function.
- Patients must be able to swallow medication.
- Pregnancy Testing. Women of childbearing potential are required to have a negative
serum pregnancy test within 10-14 days and within 24 hours prior to the first dose
of either drug (serum or urine).
- Ability to understand and the willingness to sign a written informed consent
document.
- Patient without any legal protection measure and having health coverage.
- Patients with solid tumors (breast adenocarcinomas, colorectal adenocarcinomas,
renal cell carcinomas, gastric and oesophageal adenocarcinomas, pancreatic cancers,
hepatocellular carcinoma, ovarian and Fallopian tube adenocarcinomas, primary
peritoneal carcinoma, endometrial and cervix cancers, non-small cell lung carcinoma,
melanoma, thyroid carcinomas) resistant or not amenable to standard treatments
- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as
>20 mm with conventional techniques or as >10 mm with spiral CT scan.
- Patients must have assessable primary or metastatic lesion using dynamic contrast
enhanced ultrasound
- Patients must be willing to have two tumor biopsies performed (one before study
start and one during study treatment), unless medically contraindicated.
- No previous treatment with sorafenib and everolimus. Patients may have been
previously treated with one experimental drug: sorafenib or everolimus.
- No other limitation on prior therapy. However, there must be at least a 4 week
interval between initiation of study treatment and any prior radiotherapy or
systemic therapy, 6 weeks if the last regimen included BCNU or mitomycin C.
- Males and females aged >18 years.
- Life expectancy of greater than 12 weeks.
- ECOG performance status ≤ 2 (Karnofsky > 70%; see Appendix A).
- Patients must have normal organ and marrow function.
- Patients must be able to swallow medication.
- Pregnancy Testing. Women of childbearing potential are required to have a negative
serum pregnancy test within 10-14 days and within 24 hours prior to the first dose
of either drug (serum or urine).
- Ability to understand and the willingness to sign a written informed consent
document.
- Patient without any legal protection measure and having health coverage.
- Previous treatment with sorafenib and everolimus.
- Patients may not be receiving any other investigational agents.
- Patients with known brain metastases should be excluded from this clinical trial.
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to everolimus or sorafenib or other agents used in the study.
- Patients taking medications with narrow therapeutic indices that are metabolized by
cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible.
- Patients who are taking concurrent medications that are strong inducers/inhibitors
of CYP3A4 should be switched to alternative medications to minimize any potential
risk. If such patients cannot be switched to alternative medications, they will be
ineligible to participate in this study. A list of prohibited CYP3A4 inducers and
inhibitors is provided in Appendix D.
- Patients with malabsorption syndrome or other condition that would interfere with
intestinal absorption.
- Patients who are serologically positive for Hepatitis A, B or C, or have other forms
of hepatitis or cirrhosis are ineligible, except for patients with hepatocellular
carcinoma. Patients with hepatocellular carcinoma with Child Pugh B or C score.
- Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia,
hypophosphatemia or hypokalemia defined as less than the lower limit of normal for
the institution, despite adequate electrolyte supplementation are excluded from this
study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia other than chronic, stable atrial fibrillation, or psychiatric
illness/social situations that would limit compliance with study requirements.
- HIV-positive patients on combination antiretroviral therapy are ineligible because
of the potential for pharmacokinetic interactions with everolimus.
- Cardiovascular: Patients with QTc ≥ 470 mSec, as measured by ECG using Bazett's
formula for both male and female are ineligible.
- Patients who have not recovered from side effects of previous systemic anticancer
therapy to ≤ CTCAE Grade 2 prior to the first dose of combination.