EVESOR: a Phase 1 Trial of Everolimus and Sorafenib (EVESOR)

August 27, 2013 updated by: Hospices Civils de Lyon

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 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The present 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Lyon, France, 69002
        • Recruiting
        • Hospices Civils de Lyon

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Schedule A
Everolimus run-in period followed by continuous administration of everolimus and sorafenib
Drug: Everolimus and sorafenib
Everolimus will be given alone during a 2 week run-in period before starting sorafenib. Subsequently sorafenib will be administered twice a day while everolimus will be given once a day continuously.
Drug: Everolimus and sorafenib
Sorafenib will be given alone during a 2 week run-in period before starting everolimus. Subsequently sorafenib will be administered twice a day while everolimus will be given once a day continuously.
Drug: Everolimus and sorafenib
Bid sorafenib will be given every other week alternating with 1 week qd everolimus. Doses will be escalated.
Drug: Everolimus and sorafenib
Sorafenib will be given twice a day for 3 days-on 4 days-off while everolimus will be administered continuously on a daily basis. Doses will be escalated.
Active Comparator: Schedule B
Sorafenib run-in period followed by continuous administration of everolimus and sorafenib
Drug: Everolimus and sorafenib
Everolimus will be given alone during a 2 week run-in period before starting sorafenib. Subsequently sorafenib will be administered twice a day while everolimus will be given once a day continuously.
Drug: Everolimus and sorafenib
Sorafenib will be given alone during a 2 week run-in period before starting everolimus. Subsequently sorafenib will be administered twice a day while everolimus will be given once a day continuously.
Drug: Everolimus and sorafenib
Bid sorafenib will be given every other week alternating with 1 week qd everolimus. Doses will be escalated.
Drug: Everolimus and sorafenib
Sorafenib will be given twice a day for 3 days-on 4 days-off while everolimus will be administered continuously on a daily basis. Doses will be escalated.
Experimental: Schedule C
Everolimus and sorafenib in alternance
Drug: Everolimus and sorafenib
Everolimus will be given alone during a 2 week run-in period before starting sorafenib. Subsequently sorafenib will be administered twice a day while everolimus will be given once a day continuously.
Drug: Everolimus and sorafenib
Sorafenib will be given alone during a 2 week run-in period before starting everolimus. Subsequently sorafenib will be administered twice a day while everolimus will be given once a day continuously.
Drug: Everolimus and sorafenib
Bid sorafenib will be given every other week alternating with 1 week qd everolimus. Doses will be escalated.
Drug: Everolimus and sorafenib
Sorafenib will be given twice a day for 3 days-on 4 days-off while everolimus will be administered continuously on a daily basis. Doses will be escalated.
Experimental: Schedule D
Continuous administration of everolimus and intermittent administration of sorafenib
Drug: Everolimus and sorafenib
Everolimus will be given alone during a 2 week run-in period before starting sorafenib. Subsequently sorafenib will be administered twice a day while everolimus will be given once a day continuously.
Drug: Everolimus and sorafenib
Sorafenib will be given alone during a 2 week run-in period before starting everolimus. Subsequently sorafenib will be administered twice a day while everolimus will be given once a day continuously.
Drug: Everolimus and sorafenib
Bid sorafenib will be given every other week alternating with 1 week qd everolimus. Doses will be escalated.
Drug: Everolimus and sorafenib
Sorafenib will be given twice a day for 3 days-on 4 days-off while everolimus will be administered continuously on a daily basis. Doses will be escalated.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Safety (dose limiting toxicities) as well as the recommended doses & dosing schedules for phase 2 trials in adult patients with advanced solid tumors.
Time Frame: Patients will be evaluated for dose limiting toxicities during the first 28-day cycle.
Patients will be evaluated for dose limiting toxicities during the first 28-day cycle.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetic (PK) parameters of everolimus in combination with sorafenib
Time Frame: During the first 28-day cycle
Search for interactions
During the first 28-day cycle

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Response rate
Time Frame: Every 2 weeks
Preliminary antitumor activity of everolimus-sorafenib combination
Every 2 weeks
Pharmacodynamic (PD) effects
Time Frame: During the first 28-day cycle
Pharmacodynamic (PD) effects of everolimus in combination with sorafenib on PI3K-AKT-mTor and RAS-RAF-ERK signaling pathways in tumor and surrogate tissues
During the first 28-day cycle
PK-PD relationships
Time Frame: During the first 28-day cycle
Relationships between PK and PD effects measured in tumor and surrogate tissues
During the first 28-day cycle

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hospices Civils de Lyon

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: BENOIT YOU, MD PhD, Hospices Civils de Lyon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2013

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 13, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 27, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 30, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 30, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 27, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2012-716

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