PRednisone Plus EVerolimus in Patients With Metastatic Renal Cell Cancer After Failure of VEGFR -TKI (PREV)

January 12, 2018 updated by: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 2

Contacts and Locations

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

Study Locations

  • Italy
      • Rimini, Italy, 47923
        • Oncologia Medica, PO Rimini-Cattolica, AUSL della Romagna
    • FC
      • Meldola, FC, Italy, 47014
        • U.O Oncologia Medica, IRST IRCCS
    • RA
      • Faenza, RA, Italy, 48121
        • Oncologia Medica, PO Faenza, AUSL della Romagna
      • Ravenna, RA, Italy, 48121
        • Oncologia Medica, PO RAVENNA, AUSL della Romagna

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age ≥ 18 years old
  2. Patients with histopathologically confirmed diagnosis of renal cell carcinoma
  3. Patients with renal cell carcinoma who failed at least one VEGFR TKI
  4. Patients with adequate bone marrow function defined as ANC ≥ 1.5 x 109/L, Platelets ≥ 80 x 109/L, Hb >9 g/dL
  5. 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
  6. Patients with adequate renal function defined as serum creatinine ≤ 1.5 x ULN
  7. Patients who give a written informed consent obtained according to local guidelines

Exclusion Criteria:

  1. CNS disease OR patients with presence or history of central nervous system (CNS) lymphoma
  2. 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.
  3. Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
  4. Patients with uncontrolled hyperlipidemia (≥ Grade 3 hyperlipidemia despite optimal supportive medical therapy)
  5. Patients with an active, bleeding diathesis
  6. Previous organ transplantation

  7. 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.
  8. A known history of HIV seropositivity
  9. 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.
  10. Patients unwilling to or unable to comply with the protocol

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Prednisone + Everolimus
Drug: 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.

Other Names:
  • prednisone
  • everolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
up to 36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: up to 36 months
the sum of partial responses plus complete responses
up to 36 months
Progression free survival (PFS)
Time Frame: up to 36 months
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.
up to 36 months
Overall survival (OS)
Time Frame: up to 36 months
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.
up to 36 months

Collaborators and Investigators

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

Sponsor

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

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 (Actual)

September 22, 2015

Primary Completion (Actual)

May 5, 2017

Study Completion (Actual)

September 1, 2017

Study Registration Dates

First Submitted

June 19, 2015

First Submitted That Met QC Criteria

June 23, 2015

First Posted (Estimate)

June 24, 2015

Study Record Updates

Last Update Posted (Actual)

January 16, 2018

Last Update Submitted That Met QC Criteria

January 12, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRST189.04

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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