Metastatic or Locally Advanced Solid TumorsPhase 1EVESORNCT01932177
EVESOR: a Phase 1 Trial of Everolimus and Sorafenib
A Phase 1 study testing Everolimus and sorafenib in people with Metastatic or Locally Advanced Solid Tumors, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic or Locally Advanced Solid Tumors
- What is being tested?
- Everolimus and sorafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2013to Oct 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Being tested
- Everolimus and sorafenib
- Keywords
- Everolimus ; Sorafenib ; Phase 1 trial ; Solid tumor
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus and sorafenibDrug
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.
Everolimus and sorafenibDrug
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.
Everolimus and sorafenibDrug
Bid sorafenib will be given every other week alternating with 1 week qd everolimus. Doses will be escalated.
Everolimus and sorafenibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Schedule A | Active comparator | Everolimus run-in period followed by continuous administration of everolimus and sorafenib Receives: Drug: Everolimus and sorafenib |
| Schedule B | Active comparator | Sorafenib run-in period followed by continuous administration of everolimus and sorafenib Receives: Drug: Everolimus and sorafenib |
| Schedule C | Experimental | Everolimus and sorafenib in alternance Receives: Drug: Everolimus and sorafenib |
| Schedule D | Experimental | Continuous administration of everolimus and intermittent administration of sorafenib Receives: Drug: Everolimus and sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (dose limiting toxicities) as well as the recommended doses & dosing schedules for phase 2 trials in adult patients with advanced solid tumors.
Measured: Patients will be evaluated for dose limiting toxicities during the first 28-day cycle.
Secondary outcomes (1)
Pharmacokinetic (PK) parameters of everolimus in combination with sorafenib
Search for interactions
Measured: During the first 28-day cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2013 (estimated)
- Study startApr 2013
- Primary completionMay 2013
- Study completionOct 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Metastatic or Locally Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- BENOIT YOU, MD PhD, Study director, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01932177
- Sponsor's protocol ID
- 2012-716
- Acronym
- EVESOR
- Status last verified
- Apr 2013
- First submitted
- 13 May 2013
- Last updated
- 30 Aug 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Puszkiel A, You B, Payen L, Lopez J, Guitton J, Rousset P, Fontaine J, Peron J, Maillet D, Tartas S, Bonnin N, Trillet-Lenoir V, Colomban O, Augu-Denechere D, Freyer G, Tod M. A PK-PD model linking biomarker dynamics to progression-free survival in patients treated with everolimus and sorafenib combination therapy, EVESOR phase I trial. Cancer Chemother Pharmacol. 2023 May;91(5):413-425. doi: 10.1007/s00280-023-04520-z. Epub 2023 Apr 3.
PubMed 37010549Varnier R, Puszkiel A, Tod M, Calattini S, Payen L, Lopez J, Guitton J, Schwiertz V, Fontaine J, Peron J, Maillet D, Tartas S, Bonnin N, Colomban O, Augu-Denechere D, Freyer G, You B. Clinical results of the EVESOR trial, a multiparameter phase I trial of everolimus and sorafenib combination in solid tumors. Cancer Chemother Pharmacol. 2023 May;91(5):361-373. doi: 10.1007/s00280-023-04508-9. Epub 2023 Feb 25.
PubMed 36840749El-Madani M, Colomban O, Tod M, Maillet D, Peron J, Rodriguez-Lafrasse C, Badary OA, Valette PJ, Lefort T, Cassier P, El-Shenawy SM, El-Demerdash E, Hommel-Fontaine J, Guitton J, Gagnieu MC, Ibrahim BM, Barrois C, Freyer G, You B. EVESOR, a model-based, multiparameter, Phase I trial to optimize the benefit/toxicity ratio of everolimus and sorafenib. Future Oncol. 2017 Apr;13(8):679-693. doi: 10.2217/fon-2016-0357. Epub 2017 Jan 12.
PubMed 28076966
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01932177
- Acronym / sponsor ID
- EVESOR / 2012-716
- Keywords
- Everolimus ; Sorafenib ; Phase 1 trial ; Solid tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- May 2013 (actual)
- Study completion
- Oct 2015 (estimated)
- First posted
- 30 Aug 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Schedule A | Active comparator | Drug: Everolimus and sorafenibEverolimus run-in period followed by continuous administration of everolimus and sorafenib |
| Schedule B | Active comparator | Drug: Everolimus and sorafenibSorafenib run-in period followed by continuous administration of everolimus and sorafenib |
| Schedule C | Experimental | Drug: Everolimus and sorafenibEverolimus and sorafenib in alternance |
| Schedule D | Experimental | Drug: Everolimus and sorafenibContinuous administration of everolimus and intermittent administration of sorafenib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Everolimus and sorafenibEverolimus 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 | Schedule A, Schedule B, Schedule C, Schedule D |
| Everolimus and sorafenibSorafenib 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 | Schedule A, Schedule B, Schedule C, Schedule D |
| Everolimus and sorafenibBid sorafenib will be given every other week alternating with 1 week qd everolimus. Doses will be escalated. | Drug | Schedule A, Schedule B, Schedule C, Schedule D |
| Everolimus and sorafenibSorafenib 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. | Drug | Schedule A, Schedule B, Schedule C, Schedule D |
Primary outcome
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.
1 secondary outcome
Pharmacokinetic (PK) parameters of everolimus in combination with sorafenib
Time frame: During the first 28-day cycle
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2013.
- Derived from this study: PubMed 37010549Puszkiel A, You B, Payen L, Lopez J, Guitton J, Rousset P, Fontaine J, Peron J, Maillet D, Tartas S, Bonnin N, Trillet-Lenoir V, Colomban O, Augu-Denechere D, Freyer G, Tod M. A PK-PD model linking biomarker dynamics to progression-free survival in patients treated with everolimus and sorafenib combination therapy, EVESOR phase I trial. Cancer Chemother Pharmacol. 2023 May;91(5):413-425. doi: 10.1007/s00280-023-04520-z. Epub 2023 Apr 3.
- Derived from this study: PubMed 36840749Varnier R, Puszkiel A, Tod M, Calattini S, Payen L, Lopez J, Guitton J, Schwiertz V, Fontaine J, Peron J, Maillet D, Tartas S, Bonnin N, Colomban O, Augu-Denechere D, Freyer G, You B. Clinical results of the EVESOR trial, a multiparameter phase I trial of everolimus and sorafenib combination in solid tumors. Cancer Chemother Pharmacol. 2023 May;91(5):361-373. doi: 10.1007/s00280-023-04508-9. Epub 2023 Feb 25.
- Derived from this study: PubMed 28076966El-Madani M, Colomban O, Tod M, Maillet D, Peron J, Rodriguez-Lafrasse C, Badary OA, Valette PJ, Lefort T, Cassier P, El-Shenawy SM, El-Demerdash E, Hommel-Fontaine J, Guitton J, Gagnieu MC, Ibrahim BM, Barrois C, Freyer G, You B. EVESOR, a model-based, multiparameter, Phase I trial to optimize the benefit/toxicity ratio of everolimus and sorafenib. Future Oncol. 2017 Apr;13(8):679-693. doi: 10.2217/fon-2016-0357. Epub 2017 Jan 12.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
BENOIT YOU, MD PhD study director
Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Everolimus and sorafenib in people with Metastatic or Locally Advanced Solid Tumors, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact BENOIT YOU, MD PhD (+33.4.78.86.43.18, benoit.you@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01932177, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2013.