Metastatic Renal CancerPhase 2PREVNCT02479490
PRednisone Plus EVerolimus in Patients With Metastatic Renal Cell Cancer After Failure of VEGFR -TKI
A Phase 2 study testing Prednisone + Everolimus in people with Metastatic Renal Cancer, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 4 sites in Italy.
Trial summary
This is a multicenter prospective study that includes all patients with metastatic Renal Cell Cancer (RCC) pre- treated with VEGFR TKI in eight Italian cancer centers. Everolimus is formulated as tablets of 5-10 mg strength, blister-packed under aluminium foil in units of 10 tablets. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Renal Cancer
- What is being tested?
- Prednisone + Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 4 sitesItaly
- Study dates
- 22 Sep 2015to Sep 2017
- Phase
- Phase 2
- 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
- Age ≥ 18 years old
- Patients with histopathologically confirmed diagnosis of renal cell carcinoma
- Patients with renal cell carcinoma who failed at least one VEGFR TKI
- Patients with adequate bone marrow function defined as ANC ≥ 1.5 x 109/L, Platelets ≥ 80 x 109/L, Hb >9 g/dL
- Patients with adequate liver function defined as serum bilirubin ≤ 1.5 x ULN, ALT and AST ≤ 2.5x ULN. Patients with known liver metastases who have an AST and ALT ≤ 5x ULN
- Patients with adequate renal function defined as serum creatinine ≤ 1.5 x ULN
- Patients who give a written informed consent obtained according to local guidelines
Who cannot join
- CNS disease OR patients with presence or history of central nervous system (CNS) lymphoma
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg for adrenal insufficiency). However, patients receiving corticosteroids must be on a stable dose for ≥ 4 weeks prior to the first dose of everolimus. Topical or inhaled corticosteroids are permitted.
- Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
- Patients with uncontrolled hyperlipidemia (≥ Grade 3 hyperlipidemia despite optimal supportive medical therapy)
- Patients with an active, bleeding diathesis
- Previous organ transplantation
Show all 17Show fewer
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
- severely impaired lung function (spirometry and DLCO that is 50% of the normal predicted value and/or Oxygen saturation that is 88% or less at rest, in room air)
- uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
- any active (acute or chronic) or uncontrolled infections/disorders
- non malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with this study therapy
- liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
- Note: a detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV DNA and HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.
- A known history of HIV seropositivity
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not willing to use effective birth control methods. If barrier contraceptives are used, they must be continued throughout the treatment by both sexes.
- Patients unwilling to or unable to comply with the protocol
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
Oncologia Medica, PO Faenza, AUSL della Romagna
Faenza, RA, 48121
U.O Oncologia Medica, IRST IRCCS
Meldola, FC, 47014
Oncologia Medica, PO RAVENNA, AUSL della Romagna
Ravenna, RA, 48121
Oncologia Medica, PO Rimini-Cattolica, AUSL della Romagna
Rimini, 47923
About this study
Official title: Phase II Study of Oral PRednisone 5 mg Bid Plus EVerolimus in Patients With Metastatic Renal Cell Cancer After Failure of Vascular Endothelial Growth Factor Receptor-tyrosine Kinase Inhibitors
This is a multicenter prospective study that includes all patients with metastatic Renal Cell Cancer (RCC) pre- treated with VEGFR TKI in eight Italian cancer centers.
Everolimus is formulated as tablets of 5-10 mg strength, blister-packed under aluminium foil in units of 10 tablets. Prednisone will be dispensed to patients at the dose of 5 mg twice daily (BID). Everolimus at dose of 10 mg (one 10 mg tablet or two 5 mg tablets). Both drugs will be self-administered orally, continuously from Day 1 (Visit 2) until progression of disease, unacceptable toxicity, death or discontinuation for any other reason.
A treatment cycle consists of 28 days.
Read the detailed description
Title Phase II study of oral PRednisone 5 mg bid plus EVerolimus in patients with metastatic renal cell cancer after failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitor (PREV study).
Short Title/ Acronym PREV Protocol Code IRST189.04 Phase Phase 2 Study Design This is a multicenter prospective study that includes all patients with metastatic RCC pre- treated with VEGFR TKI in eight Italian cancer centers.
Study Duration 2 years of recruitment and 1 year of follow-up Study Center(s) multi-center: 8 centers involved
Objectives Primary objective:
To evaluate the safety and tolerability of prednisone 5 mg bid and everolimus 10 mg/day in RCC.
Secondary objectives:
To evaluate the activity and the clinical outcome of these patients.
Exploratory objectives:
To evaluate the influence of prednisone on trough concentration of everolimus and correlation with the incidence of side effects, in particular stomatitis and non-infectious pneumonitis.
Infiammation markers such as pentraxin 3 (PTX3), IL-6, TGF-β and neutrophil-lymphocyte ratio will be correlated with clinical outcome (ORR, PFS, OS).
Number of Subjects 42 subjects Diagnosis and Main Inclusion Criteria Patients with mRCC who failed at least one VEGFR TKI.
Main Inclusion Criteria:
- Patients with renal cell carcinoma who failed at least one VEGFR TKI
- Patients with adequate bone marrow function
- Patients with adequate liver function
- Patients with adequate renal function Diagnosis and Main Inclusion Criteria (continued) Main exclusion criteria:
- CNS disease OR patients with presence or history of central nervous system (CNS) lymphoma
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg for adrenal insufficiency). However, patients receiving corticosteroids must be on a stable dose for ≥ 4 weeks prior to the first dose of everolimus. Topical or inhaled corticosteroids are permitted.
- Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
- Patients with uncontrolled hyperlipidemia (≥ Grade 3 hyperlipidemia despite optimal supportive medical therapy)
- Patients with an active, bleeding diathesis
- Previous organ transplantation
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study Study Product, Dose, Route, Regimen and duration of administration Everolimus is formulated as tablets of 5-10 mg strength, blister-packed under aluminium foil in units of 10 tablets. Prednisone will be dispensed to patients at the dose of 5 mg twice daily (BID). Everolimus at dose of 10 mg (one 10 mg tablet or two 5 mg tablets). Both drugs will be self-administered orally, continuously from Day 1 (Visit 2) until progression of disease, unacceptable toxicity, death or discontinuation for any other reason.
A treatment cycle consists of 28 days. Reference therapy Not applicable Statistical Methodology This is a multicenter prospective study that includes all patients with metastatic RCC pre- treated with VEGFR TKI in eight Italian cancer centers.
The study will be analyzed on an intent-to-treat basis. Secondary parameters will be analyzed exploratively for the intent-to-treat population.
- Conditions
- Metastatic Renal Cancer
- Being tested
- Prednisone + Everolimus
- Keywords
- metastatic renal cancer, failure of VEGFR_TKI, prednisone, everolimus
- Medical subject headings
- Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prednisone + EverolimusDrug
Also called prednisone, everolimus
Prednisone + Everolimus: Everolimus is formulated as tablets of 5-10 mg strength, blister-packed under aluminium foil in units of 10 tablets. Prednisone will be dispensed to patients at the dose of 5 mg twice daily (BID). Everolimus at dose of 10 mg (one 10 mg tablet or two 5 mg tablets). Both drugs will be self-administered orally, continuously from Day 1 (Visit 2) until progression of disease, unacceptable toxicity, death or discontinuation for any other reason.
A treatment cycle consists of 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Prednisone + Everolimus | Experimental | Prednisone + Everolimus Receives: Drug: Prednisone + Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety and tolerability evaluation (incidence of grade ≥ 2 stomatitis and non-infectious pneumonitis)
to evaluate the incidence of grade ≥ 2 stomatitis and non-infectious pneumonitis in RCC patients treated with prednisone 5 mg bid and everolimus 10 mg/day.
Measured: up to 36 months
Secondary outcomes (3)
Overall response rate (ORR)
the sum of partial responses plus complete responses
Measured: up to 36 months
Progression free survival (PFS)
time from the date of starting of the treatment to the date of the first observation of documented disease progression or death due to any cause. Patients without tumor progression at the time of analysis will be censored at their last date of tumor evaluation.
Measured: up to 36 months
Overall survival (OS)
time from the date of starting of the treatment to the date of the death due to any cause. Patients living at the time of analysis will be censored at their last date of tumor evaluation.
Measured: up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2015 (estimated)
- Study start22 Sep 2015
- Primary completion5 May 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Renal CancerStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ugo De Giorgi, MD, Principal investigator, IRST IRCCS, Meldola
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02479490
- Sponsor's protocol ID
- IRST189.04
- Acronym
- PREV
- Status last verified
- Jan 2018
- First submitted
- 19 Jun 2015
- Last updated
- 16 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Lolli C, Galla V, Schepisi G, Barone D, Burgio SL, Maugeri A, Vertogen B, Amadori D, De Giorgi U. A Phase II Study of Everolimus Plus Oral Prednisone in Patients with Metastatic Renal Cell Cancer. Oncologist. 2017 Jul;22(7):784-e74. doi: 10.1634/theoncologist.2017-0154. Epub 2017 May 25.
PubMed 28546463
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Oral PRednisone 5 mg Bid Plus EVerolimus in Patients With Metastatic Renal Cell Cancer After Failure of Vascular Endothelial Growth Factor Receptor-tyrosine Kinase Inhibitors
- ClinicalTrials.gov ID
- NCT02479490
- Acronym / sponsor ID
- PREV / IRST189.04
- Conditions
- Metastatic Renal Cancer
- Keywords
- metastatic renal cancer, failure of VEGFR_TKI, prednisone, everolimus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCSUniversity, hospital or other
- Study start
- 22 Sep 2015 (actual)
- Primary completion
- 5 May 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 24 Jun 2015 (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.
This is a multicenter prospective study that includes all patients with metastatic Renal Cell Cancer (RCC) pre- treated with VEGFR TKI in eight Italian cancer centers.
Everolimus is formulated as tablets of 5-10 mg strength, blister-packed under aluminium foil in units of 10 tablets. Prednisone will be dispensed to patients at the dose of 5 mg twice daily (BID). Everolimus at dose of 10 mg (one 10 mg tablet or two 5 mg tablets). Both drugs will be self-administered orally, continuously from Day 1 (Visit 2) until progression of disease, unacceptable toxicity, death or discontinuation for any other reason.
A treatment cycle consists of 28 days.
Detailed description
Title Phase II study of oral PRednisone 5 mg bid plus EVerolimus in patients with metastatic renal cell cancer after failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitor (PREV study).
Short Title/ Acronym PREV Protocol Code IRST189.04 Phase Phase 2 Study Design This is a multicenter prospective study that includes all patients with metastatic RCC pre- treated with VEGFR TKI in eight Italian cancer centers.
Study Duration 2 years of recruitment and 1 year of follow-up Study Center(s) multi-center: 8 centers involved
Objectives Primary objective:
To evaluate the safety and tolerability of prednisone 5 mg bid and everolimus 10 mg/day in RCC.
Secondary objectives:
To evaluate the activity and the clinical outcome of these patients.
Exploratory objectives:
To evaluate the influence of prednisone on trough concentration of everolimus and correlation with the incidence of side effects, in particular stomatitis and non-infectious pneumonitis.
Infiammation markers such as pentraxin 3 (PTX3), IL-6, TGF-β and neutrophil-lymphocyte ratio will be correlated with clinical outcome (ORR, PFS, OS).
Number of Subjects 42 subjects Diagnosis and Main Inclusion Criteria Patients with mRCC who failed at least one VEGFR TKI.
Main Inclusion Criteria:
- Patients with renal cell carcinoma who failed at least one VEGFR TKI
- Patients with adequate bone marrow function
- Patients with adequate liver function
- Patients with adequate renal function Diagnosis and Main Inclusion Criteria (continued) Main exclusion criteria:
- CNS disease OR patients with presence or history of central nervous system (CNS) lymphoma
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg for adrenal insufficiency). However, patients receiving corticosteroids must be on a stable dose for ≥ 4 weeks prior to the first dose of everolimus. Topical or inhaled corticosteroids are permitted.
- Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
- Patients with uncontrolled hyperlipidemia (≥ Grade 3 hyperlipidemia despite optimal supportive medical therapy)
- Patients with an active, bleeding diathesis
- Previous organ transplantation
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study Study Product, Dose, Route, Regimen and duration of administration Everolimus is formulated as tablets of 5-10 mg strength, blister-packed under aluminium foil in units of 10 tablets. Prednisone will be dispensed to patients at the dose of 5 mg twice daily (BID). Everolimus at dose of 10 mg (one 10 mg tablet or two 5 mg tablets). Both drugs will be self-administered orally, continuously from Day 1 (Visit 2) until progression of disease, unacceptable toxicity, death or discontinuation for any other reason.
A treatment cycle consists of 28 days. Reference therapy Not applicable Statistical Methodology This is a multicenter prospective study that includes all patients with metastatic RCC pre- treated with VEGFR TKI in eight Italian cancer centers.
The study will be analyzed on an intent-to-treat basis. Secondary parameters will be analyzed exploratively for the intent-to-treat population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Prednisone + Everolimus | Experimental | Drug: Prednisone + EverolimusPrednisone + Everolimus |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥ 18 years old
- Patients with histopathologically confirmed diagnosis of renal cell carcinoma
- Patients with renal cell carcinoma who failed at least one VEGFR TKI
- Patients with adequate bone marrow function defined as ANC ≥ 1.5 x 109/L, Platelets ≥ 80 x 109/L, Hb >9 g/dL
- Patients with adequate liver function defined as serum bilirubin ≤ 1.5 x ULN, ALT and AST ≤ 2.5x ULN. Patients with known liver metastases who have an AST and ALT ≤ 5x ULN
Key exclusion criteria (17 listed)
- CNS disease OR patients with presence or history of central nervous system (CNS) lymphoma
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg for adrenal insufficiency). However, patients receiving corticosteroids must be on a stable dose for ≥ 4 weeks prior to the first dose of everolimus. Topical or inhaled corticosteroids are permitted.
- Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
- Patients with uncontrolled hyperlipidemia (≥ Grade 3 hyperlipidemia despite optimal supportive medical therapy)
- Patients with an active, bleeding diathesis
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 |
|---|---|---|
| Prednisone + EverolimusAlso: prednisone, everolimusPrednisone + Everolimus: Everolimus is formulated as tablets of 5-10 mg strength, blister-packed under aluminium foil in units of 10 tablets. Prednisone will be dispensed to patients at the dose of 5 mg twice daily (BID). Everolimus at dose of 10 mg (one 10 mg tablet or two 5 mg tablets). Both drugs will be self-administered orally, continuously from Day 1 (Visit 2) until progression of disease, unacceptable toxicity, death or discontinuation for any other reason. A treatment cycle consists of 28 days. | Drug | Prednisone + Everolimus |
Primary outcome
safety and tolerability evaluation (incidence of grade ≥ 2 stomatitis and non-infectious pneumonitis)
Time frame: up to 36 months
to evaluate the incidence of grade ≥ 2 stomatitis and non-infectious pneumonitis in RCC patients treated with prednisone 5 mg bid and everolimus 10 mg/day.
3 secondary outcomes
Overall response rate (ORR)
Time frame: up to 36 months
Progression free survival (PFS)
Time frame: up to 36 months
Overall survival (OS)
Time frame: up to 36 months
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2018.
- Derived from this study: PubMed 28546463Lolli C, Galla V, Schepisi G, Barone D, Burgio SL, Maugeri A, Vertogen B, Amadori D, De Giorgi U. A Phase II Study of Everolimus Plus Oral Prednisone in Patients with Metastatic Renal Cell Cancer. Oncologist. 2017 Jul;22(7):784-e74. doi: 10.1634/theoncologist.2017-0154. Epub 2017 May 25.
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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.
Ugo De Giorgi, MD principal investigator
IRST IRCCS, Meldola
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Prednisone + Everolimus in people with Metastatic Renal Cancer, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 4 sites in Italy.
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 7 inclusion and 17 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: stopped early, as of the sponsor's last update on 16 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early. Results are not available in the source record.
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?
safety and tolerability evaluation (incidence of grade ≥ 2 stomatitis and non-infectious pneumonitis) (time frame: up to 36 months). 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 NCT02479490, which also lists 1 linked publication.
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 16 Jan 2018.