Malignant Advanced Solid TumorsPhase 1EVAXNCT01334073
Study of the Combination of Axitinib Plus Everolimus in Patients With Malignant Advanced Solid Tumors
A Phase 1 study testing Axitinib plus everolimus in people with Malignant Advanced Solid Tumors and Carcinoma, Renal Cell, run by University Hospital, Bordeaux at 2 sites in France.
Trial summary
The aim of the study is to determine the MTD of the combination of everolimus plus axitinib in solid tumors, especially RCC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Advanced Solid Tumors, Carcinoma, Renal Cell
- What is being tested?
- Axitinib plus everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 2 sitesFrance
- Study dates
- Mar 2011to Jan 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
- Histologically proven advanced adult solid tumors, with the exception of Hodgkin and non Hodgkin lymphoma. Patients with hepatocellular carcinomas (HCC) may be enrolled without histological documentation if they meet the consensus non-invasive diagnostic criteria.
- Failure or contra-indication of all standard therapies, except for the patients with advanced renal cell carcinoma, enrolled at the recommended dose who will be naïve of previous lines of therapy while metastatic.
- Age > 18 years
- ECOG Performance status (PS) 0-1
- Life expectancy > 3 months
- Measurable/evaluable disease according to RECIST CRITERIA version 1.0
Show all 21Show fewer
- Acceptable biological values: Hemoglobin > 10g /dL; neutrophils > 1.5 x 109/L; platelets > 100 x 109/L, AST and ALT < 2.5 x the upper normal limits (UNL), or < 5 x UNL in case of liver metastases, GGT < 3 x the upper normal limits (UNL), PAL < 2.5 x the upper normal limits (UNL), or < 5 x UNL in case of liver metastases, serum bilirubin < 1.5 x ULN, creatinine clearance (Cockroft \& Gault formula) > 60 mL/min.
- 24 hours proteinuria ≤ 1 g/24 h
- Albumin > 30 g/l
- Amylase and lipase ≤ 1.5 UNL
- Electrolytes (calcium, sodium, potassium, chlore, magnesium, phosphate) in the normal range. Supplementation could be possible before study entry.
- Total cholesterol ≤ 2.5 UNL
- Triglycerides ≤ 2.5 UNL
- BP < 140/90
- Washout period from last anticancer therapy, including radiation and surgery > 3 weeks and recovery of toxicities to NCI-CTC grade < 1.
- Written informed Consent.
- Use of effective contraceptive method (Intrauterine device, oral combined contraceptive) for women of child-bearing age or whose partner is included in the trial.
- Patient with french social security.
- Additional inclusion criteria before the association axitinib plus everolimus period
- No toxicity with NCI-CTC grade > 2 at the end of axitinib alone period just before starting axitinib and everolimus (cycle 1)
- BP < 140/ 90
Who cannot join
- Brain metastasis
- Severe underlying cardiovascular disease, even medically controlled, such as angina pectoris, myocardial infarction, cardiac insufficiency, cardiac failure, cerebral strokes, lower limb ischemic disease, thromboembolic disease, and any patient, who, in the investigator's opinion is at high risk for arterial or venous thromboembolism.
- Hepatitis B or C carrier or at a chronic state
- Uncontrolled hypertension, or diabetes mellitus despite medical treatment.
- Inability to swallow pills
- Unresolved pneumopathy, no need for antibiotherapy
Show all 10Show fewer
- Any medical or social condition, which; in the investigator's opinion, would jeopardize patient's safety, patient's compliance to the protocol, or the interpretation of study results. These conditions include (but are not limited to): severe infection, cardiac failure, chronic gastrointestinal disease compromising oral drug absorption, psychiatric illnesses, foreseeable poor treatment compliance with oral medications, patients living far away from the investigational centers, etc…
- Hypersensitivity to Axitinib or Everolimus
- Participation to another clinical trial, or use of an unapproved medication within 4 weeks prior to study treatment initiation.
- Pregnant or lactating women.
Trial locations and contacts
2 sites in 1 country.
France2 sites
Professeur Alain RAVAUD
Bordeaux, 33000
Professeur Jean-Pierre DELORD
Toulouse, 31000
About this study
Official title: Phase I Study of the Combination of Axitinib (AX) Plus Everolimus (EV) in Patients With Malignant Advanced Solid Tumors
The aim of the study is to determine the MTD of the combination of everolimus plus axitinib in solid tumors, especially RCC.
Read the detailed description
Phase I study of the combination of axitinib (AX) plus everolimus (EV) in patients with malignant advanced solid tumors.
- To determine the recommended dose for phase II study of the combination of AX + EV
- To determine the safety profile and predictive factors for toxicity, pharmacokinetics (PK), and efficacy in adult solid tumors.
- To assess functional vascular imaging (FVI) as surrogate marker of activity, biomarkers predictive of activity and preliminary efficacy data in metastatic RCC, untreated with antiangiogenics.
Phase I, multicentre, open-label, non-randomized, sequential algorithm based dose-finding (3+3), clinical study in successive cohorts of patients.
Patients will take both drugs orally, every day, without planned rest period (AX bid and EV once a day). By convention one cycle is 28 days. At the first cycle patients will take one week of AX single agent before starting EV. Patients will be treated at increasing dose levels (DLs) in successive cohorts of 3-6 patients according to the number of patients with dose limiting toxicities (DLT) until the maximum tolerated dose (MTD; i.e. the DL at which <= 1/6 patient experiences a DLT during the first cycle). All decision concerning qualification for DLT, dose escalation, study termination, inclusion of additional patients, will be taken by a Trial Monitoring Committee..
The MTD will not be higher than the recommended dose of each single agent. Six additional patients will be entered at the MTD to confirm the feasibility of the dose and preliminarily assess the efficacy of the combination in patients with RCC untreated with antiangiogenics.
Three levels of dose will be explored.
- Being tested
- Axitinib plus everolimus
- Keywords
- Phase I, Axitinib, Everolimus, Maximum tolerated dose (MTD), solid tumor, Renal cell cancer (RCC), Pharmacokinetics (PK/PD)
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Axitinib plus everolimusDrug
Patients will take both drugs orally, every day, without planned rest period (AX bid and EV once a day). By convention one cycle is 28 days. At the first cycle patients will take one week of AX single agent before starting EV. Patients will be treated at increasing dose levels (DLs) in successive cohorts of 3-6 patients according to the number of patients with dose limiting toxicities (DLT) until the maximum tolerated dose
| Study group | Role | What they receive |
|---|---|---|
| Axitinib plus everolimus | Experimental | Not described Receives: Drug: Axitinib plus everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with DLT (dose limiting toxicity) during the first cycle (first 28 days of the combination of both study compounds), per dose level explored
A DLT will be one of the following adverse events, with a possible relationship to the study medications
- Febrile, related bleeding or any grade 4 neutropenia or thrombocytopenia,
- grade 3 non-hematological toxicity, unless adequately treated with usual symptomatic therapy
- grade 4 non-hematological toxicity
- study treatment interruption > 2 weeks, inability to deliver at least 80% of the intended doses of axitinib and/or everolimus between day 8 and 35 due to toxicity.
Measured: during cycle 1
Secondary outcomes (5)
Adverse event (AE) will be graded according to NCI-CTC criteria V3
Number of AE per patient, per grade, per cycle and per dose level, proportion
Measured: After each cycle of treatement
Best response rate will be assessed according to RECIST criteria, during the follow-up
Frequency (total, per dose level), proportion
Measured: Every other cycle of treatment
Rate of non-tumor progression at 16 weeks
Frequency (total, per dose level), proportion
Measured: at 16 weeks
Progression-free Survival (PFS) defined as the time between study treatment initiation and either tumor progression or death, regardless of the cause, whichever occurs first and PFS at 1 year
Frequency (total, per dose level), probability
Measured: 1 year
Comparison of PK parameters
Plasma PK using peak concentration (Cmax), area under the concentration versus time curve (AUC), volume of distribution at steady state (Vdss), plasma clearance (CL) and plasma half-life (t1/2). PK parameters will be compared to severe (grade 3-4) AEs, tumor responses and non-tumor progression at 16 weeks. PK parameters of axitinib combined to everolimus (day 15) will be compared to PK parameters of axitinib alone in the same patient (day 1). PK of everolimus combined to axitinib (day 15) will be compared to historical data of everolimus alone
Measured: day 1 (axitinib alone) and day 15 (everolimus combined with axitinib)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2011 (estimated)
- Study startMar 2011
- Primary completionMay 2013
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Malignant Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alain RAVAUD, Principal investigator, University Hospital, BordeauxAdélaïde Doussau, Dr, Study chair, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01334073
- Sponsor's protocol ID
- CHUBX 2010/09
- Other IDs
- 2010-021280-32
- Acronym
- EVAX
- Status last verified
- Jul 2015
- First submitted
- 5 Apr 2011
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Su Y, Amiri KI, Horton LW, Yu Y, Ayers GD, Koehler E, Kelley MC, Puzanov I, Richmond A, Sosman JA. A phase I trial of bortezomib with temozolomide in patients with advanced melanoma: toxicities, antitumor effects, and modulation of therapeutic targets. Clin Cancer Res. 2010 Jan 1;16(1):348-57. doi: 10.1158/1078-0432.CCR-09-2087. Epub 2009 Dec 22.
PubMed 20028756O'Reilly T, Lane HA, Wood JM, Schnell C, Littlewood-Evans A, Brueggen J, McSheehy PM. Everolimus and PTK/ZK show synergistic growth inhibition in the orthotopic BL16/BL6 murine melanoma model. Cancer Chemother Pharmacol. 2011 Jan;67(1):193-200. doi: 10.1007/s00280-010-1307-z. Epub 2010 May 30.
PubMed 20512579Choueiri TK. Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. Curr Opin Investig Drugs. 2008 Jun;9(6):658-71.
PubMed 18516765Ravaud A, Gomez-Roca C, Picat MQ, Digue L, Chevreau C, Gimbert A, Chauzit E, Sitta R, Cornelis F, Asselineau J, Aziza R, Daste A, Quemener C, Baud J, Bikfalvi A, Pedenon-Perichout D, Doussau A, Molimard M, Delord JP. Phase I study of axitinib and everolimus in metastatic solid tumours and extension to metastatic renal cell carcinoma: Results of EVAX study. Eur J Cancer. 2017 Nov;85:39-48. doi: 10.1016/j.ejca.2017.07.031. Epub 2017 Sep 5.
PubMed 28886476
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of the Combination of Axitinib (AX) Plus Everolimus (EV) in Patients With Malignant Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01334073
- Acronym / sponsor ID
- EVAX / CHUBX 2010/09
- Keywords
- Phase I, Axitinib, Everolimus, Maximum tolerated dose (MTD), solid tumor, Renal cell cancer (RCC), Pharmacokinetics (PK/PD)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- May 2013 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 12 Apr 2011 (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.
The aim of the study is to determine the MTD of the combination of everolimus plus axitinib in solid tumors, especially RCC.
Detailed description
Phase I study of the combination of axitinib (AX) plus everolimus (EV) in patients with malignant advanced solid tumors.
- To determine the recommended dose for phase II study of the combination of AX + EV
- To determine the safety profile and predictive factors for toxicity, pharmacokinetics (PK), and efficacy in adult solid tumors.
- To assess functional vascular imaging (FVI) as surrogate marker of activity, biomarkers predictive of activity and preliminary efficacy data in metastatic RCC, untreated with antiangiogenics.
Phase I, multicentre, open-label, non-randomized, sequential algorithm based dose-finding (3+3), clinical study in successive cohorts of patients.
Patients will take both drugs orally, every day, without planned rest period (AX bid and EV once a day). By convention one cycle is 28 days. At the first cycle patients will take one week of AX single agent before starting EV. Patients will be treated at increasing dose levels (DLs) in successive cohorts of 3-6 patients according to the number of patients with dose limiting toxicities (DLT) until the maximum tolerated dose (MTD; i.e. the DL at which <= 1/6 patient experiences a DLT during the first cycle). All decision concerning qualification for DLT, dose escalation, study termination, inclusion of additional patients, will be taken by a Trial Monitoring Committee..
The MTD will not be higher than the recommended dose of each single agent. Six additional patients will be entered at the MTD to confirm the feasibility of the dose and preliminarily assess the efficacy of the combination in patients with RCC untreated with antiangiogenics.
Three levels of dose will be explored.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Axitinib plus everolimus | Experimental | Drug: Axitinib plus everolimus |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Histologically proven advanced adult solid tumors, with the exception of Hodgkin and non Hodgkin lymphoma. Patients with hepatocellular carcinomas (HCC) may be enrolled without histological documentation if they meet the consensus non-invasive diagnostic criteria.
- Failure or contra-indication of all standard therapies, except for the patients with advanced renal cell carcinoma, enrolled at the recommended dose who will be naïve of previous lines of therapy while metastatic.
- Age > 18 years
- ECOG Performance status (PS) 0-1
- Life expectancy > 3 months
Key exclusion criteria (10 listed)
- Brain metastasis
- Severe underlying cardiovascular disease, even medically controlled, such as angina pectoris, myocardial infarction, cardiac insufficiency, cardiac failure, cerebral strokes, lower limb ischemic disease, thromboembolic disease, and any patient, who, in the investigator's opinion is at high risk for arterial or venous thromboembolism.
- Hepatitis B or C carrier or at a chronic state
- Uncontrolled hypertension, or diabetes mellitus despite medical treatment.
- Inability to swallow pills
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 |
|---|---|---|
| Axitinib plus everolimusPatients will take both drugs orally, every day, without planned rest period (AX bid and EV once a day). By convention one cycle is 28 days. At the first cycle patients will take one week of AX single agent before starting EV. Patients will be treated at increasing dose levels (DLs) in successive cohorts of 3-6 patients according to the number of patients with dose limiting toxicities (DLT) until the maximum tolerated dose | Drug | Axitinib plus everolimus |
Primary outcome
Proportion of patients with DLT (dose limiting toxicity) during the first cycle (first 28 days of the combination of both study compounds), per dose level explored
Time frame: during cycle 1
A DLT will be one of the following adverse events, with a possible relationship to the study medications * Febrile, related bleeding or any grade 4 neutropenia or thrombocytopenia, * grade 3 non-hematological toxicity, unless adequately treated with usual symptomatic therapy * grade 4 non-hematological toxicity * study treatment interruption > 2 weeks, inability to deliver at least 80% of the intended doses of axitinib and/or everolimus between day 8 and 35 due to toxicity.
5 secondary outcomes
Adverse event (AE) will be graded according to NCI-CTC criteria V3
Time frame: After each cycle of treatement
Best response rate will be assessed according to RECIST criteria, during the follow-up
Time frame: Every other cycle of treatment
Rate of non-tumor progression at 16 weeks
Time frame: at 16 weeks
Progression-free Survival (PFS) defined as the time between study treatment initiation and either tumor progression or death, regardless of the cause, whichever occurs first and PFS at 1 year
Time frame: 1 year
Comparison of PK parameters
Time frame: day 1 (axitinib alone) and day 15 (everolimus combined with axitinib)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- Background: PubMed 20028756Su Y, Amiri KI, Horton LW, Yu Y, Ayers GD, Koehler E, Kelley MC, Puzanov I, Richmond A, Sosman JA. A phase I trial of bortezomib with temozolomide in patients with advanced melanoma: toxicities, antitumor effects, and modulation of therapeutic targets. Clin Cancer Res. 2010 Jan 1;16(1):348-57. doi: 10.1158/1078-0432.CCR-09-2087. Epub 2009 Dec 22.
- Background: PubMed 20512579O'Reilly T, Lane HA, Wood JM, Schnell C, Littlewood-Evans A, Brueggen J, McSheehy PM. Everolimus and PTK/ZK show synergistic growth inhibition in the orthotopic BL16/BL6 murine melanoma model. Cancer Chemother Pharmacol. 2011 Jan;67(1):193-200. doi: 10.1007/s00280-010-1307-z. Epub 2010 May 30.
- Background: PubMed 18516765Choueiri TK. Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. Curr Opin Investig Drugs. 2008 Jun;9(6):658-71.
- Results publication: PubMed 28886476Ravaud A, Gomez-Roca C, Picat MQ, Digue L, Chevreau C, Gimbert A, Chauzit E, Sitta R, Cornelis F, Asselineau J, Aziza R, Daste A, Quemener C, Baud J, Bikfalvi A, Pedenon-Perichout D, Doussau A, Molimard M, Delord JP. Phase I study of axitinib and everolimus in metastatic solid tumours and extension to metastatic renal cell carcinoma: Results of EVAX study. Eur J Cancer. 2017 Nov;85:39-48. doi: 10.1016/j.ejca.2017.07.031. Epub 2017 Sep 5.
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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.
Alain RAVAUD principal investigator
University Hospital, Bordeaux
Adélaïde Doussau, Dr study chair
University Hospital, Bordeaux
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Axitinib plus everolimus in people with Malignant Advanced Solid Tumors and Carcinoma, Renal Cell, run by University Hospital, Bordeaux at 2 sites 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 21 inclusion and 10 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: finished, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with DLT (dose limiting toxicity) during the first cycle (first 28 days of the combination of both study compounds), per dose level explored (time frame: during cycle 1). 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 NCT01334073, which also lists 4 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 14 May 2026.