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Sorafenib in Elderly Patients With Metastatic Renal Cell Carcinoma (SERCC)

Primary Purpose

Metastatic Renal Cell Carcinoma

Status
Terminated
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Sorafenib
Sponsored by
Centro di Riferimento Oncologico - Aviano
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Renal Cell Carcinoma focused on measuring Renal Carcinoma, Metastatic, Sorafenib, Elderly

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Nephrectomized, metastatic Clear Cell RCC patients not suitable for cytokines or anti-angiogenesis (bevacizumab or sunitinib) therapy as first line treatment
  2. Age ≥ 65years
  3. ECOG Performance Status of ≤ 2
  4. MSKCC prognostic score, good or intermediate
  5. Life expectancy of at least 12 weeks.
  6. Subjects with at least one uni-dimensional (for RECIST) measurable lesion. Lesions must be measured by CT/MRI-scan.

  7. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of therapy:

    • Hemoglobin > 9.0 g/dl
    • Absolute neutrophil count (ANC) ≥ 1,500/mm3
    • Platelet count ≥ 100,000/μl
    • Total bilirubin ≤ 1.5 times the upper limit of normal
    • ALT and AST ≤ 2.5 x upper limit of normal (≤ 5 x upper limit of normal for patients with liver involvement of their cancer)
    • Alkaline phosphatase ≤ 4 x upper limit of normal
    • PT-INR/PT ≤ 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.]
    • Serum creatinine ≤ 1.5 x upper limit of normal.
  8. Ability to take correctly oral drugs.
  9. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  10. Written Informed Consent
  11. To be able to understand medical instruction and to fill in the patient's diary. If not, check if adequately supported by his/her family.

Exclusion Criteria:

  1. Previous first line treatment for mRCC. No adjuvant or neoadjuvant treatments are allowed.
  2. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
  3. History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring antiarrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension.
  4. History of previous or present seizure disorder requiring medication (such as steroids or anti-epileptics), organ allograft, HIV infection or chronic hepatitis B or C
  5. Active clinically serious infections (≥ grade 2 NCI-CTC version 3.0)
  6. Patients undergoing renal dialysis
  7. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.
  8. Patients with evidence or history of bleeding diathesis
  9. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  10. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
  11. Known allergy to sorafenib or one of its constituents

Sites / Locations

  • Centro di Riferimento Oncologico

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sorafenib

Arm Description

Sorafenib will be orally administered at a daily dose of 400 mg taken twice daily without food, at least one hour before or two hours after eating. Four weeks of treatments will be considered as a cycle. Each patient enrolled in the study will received medications for topical therapy. Dermatological medications will be provided free. In case of toxicities, dose reduction/interruption is permitted according to protocol. In case of disease progression Sorafenib administration will be discontinued.

Outcomes

Primary Outcome Measures

The primary aim of this trial is the evaluation of the efficacy of a patient education program in the reduction of HFSR
The primary aim is to determine the efficacy of the patient education program in reducing the incidence of HFSR(all grades).The efficacy is measured in terms of percentage of HFSR-free.Simon's methods will be used to calculate sample size(Simon R,1989).Considering the optimal two-stage design for phase II,considering a difference p1-p0=20% and fixing error probabilities(alfa=0.05 and beta=0.20),the number of patients for the first step is 16.The trial will be terminated if less than 7 HFSR-free patients will be seen.Otherwise the accrual will continue up to a total of 46 patients.

Secondary Outcome Measures

Frequency of dose discontinuation, interruption and reduction
Frequency of dose discontinuation, interruption and reduction
Incidence of any grade diarrhoea, and other adverse events
Incidence of any grade diarrhoea, and other adverse events
Overall Response Rate
Overall Response Rate according to the RECIST criteria
Progression free survival (PFR)
Progression free survival (PFR) in study population and comparison of Progression Free Survival (PFS) between age sub groups in the current study population

Full Information

First Posted
November 29, 2010
Last Updated
October 5, 2015
Sponsor
Centro di Riferimento Oncologico - Aviano
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1. Study Identification

Unique Protocol Identification Number
NCT01342627
Brief Title
Sorafenib in Elderly Patients With Metastatic Renal Cell Carcinoma
Acronym
SERCC
Official Title
Sorafenib in Elderly Patients With Metastatic Renal Cell Carcinoma (SERCC Study) Impact of Adverse Events Management in Elderly mRCC Patients Treated With Sorafenib
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Terminated
Why Stopped
low enrollment rate
Study Start Date
October 2010 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centro di Riferimento Oncologico - Aviano

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Study Design This is a multicenter, open label, first line phase II study in elderly (≥ 65 years old) metastatic Renal Cell Carcinoma (mRCC) patients not suitable for any other currently approved treatment (bevacizumab+INF, cytokines or sunitinib) except for sorafenib. Each patient treated with sorafenib enrolled in the study will be trained to observe the management tool for skin care. A study period of 3 years was estimated as follows: an enrollment period of 24 months and a further follow-up period of 12 months. Objectives of the trial Primary objective The primary aim of this trial is the evaluation of the efficacy of a patient education program in the reduction of Hand-Foot Skin Reaction (HFSR). Secondary Objectives TO assess: The frequency of dose discontinuation, interruption and reduction The incidence of any grade diarrhoea, and other adverse events The overall Response Rate according to the RECIST criteria. Progression free survival (PFR) in study population and comparison of PFS between age sub groups in the current study population
Detailed Description
Rationale of the present study For several decades, the systemic management of metastatic renal cell cancer (mRCC) was confined to the use of interferon (IFN) and interleukin-2 (IL-2). Recently, options for the medical management of mRCC have been improved through the introduction of agents targeting tumour angiogenesis or intracellular pathways mediating growth and proliferation. Among these agents are the small molecule inhibitors sorafenib (Nexavar), sunitinib (Sutent), temsirolimus (Torisel) and everolimus, and the monoclonal antibody bevacizumab (Avastin). All these targeted agents have been shown significantly to extend progression-free or overall survival or both when compared with placebo or IFN therapy in the treatment of mRCC. Adverse events are commonly observed in clinical practice by using these small molecule inhibitors in mRCC patients. Concerning the use of bevacizumab the most commonly observed adverse events are hypertension, proteinuria, bleeding and thrombosis. For sunitinib the most frequent adverse events include hand-foot syndrome, stomatitis, diarrhea, fatigue, hypothyroidism and hypertension. Most common adverse events with sorafenib are hand foot skin reaction (HFSR) rash, desquamation, fatigue, diarrhea, nausea, hypothyroidism and hypertension.Several studies and recommendations have been published in order to suggest how to manage sorafenib adverse reactions and in particular the HFSR. The aim of this study is to evaluate if patients education programs for the prevention of dermatological events (HFSR, rash, desquamation) can reduce the onset these adverse events (all grades). The reduction of dermatological adverse effects would concomitantly limit the frequencies of sorafenib dose reduction and interruptions in mRCC patients not suitable for cytokines or anti-angiogenesis (bevacizumab or sunitinib) therapy as first line treatment. Treatment Administration Sorafenib will be orally administered at a daily dose of 400 mg taken twice daily without food, at least one hour before or two hours after eating. Four weeks of treatments will be considered as a cycle. Each patient enrolled in the study will received medications for topical therapy. Dermatological medications will be provided free. In case of toxicities, dose reduction/interruption is permitted according to the flow charts/dose modifications. In case of disease progression, or unacceptable toxicities Sorafenib administration will be discontinued. The patient will be considered "out of treatment" if Sorafenib intake is stopped for more than 30 consecutive days and the patient will be considered for survival.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Renal Cell Carcinoma
Keywords
Renal Carcinoma, Metastatic, Sorafenib, Elderly

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sorafenib
Arm Type
Experimental
Arm Description
Sorafenib will be orally administered at a daily dose of 400 mg taken twice daily without food, at least one hour before or two hours after eating. Four weeks of treatments will be considered as a cycle. Each patient enrolled in the study will received medications for topical therapy. Dermatological medications will be provided free. In case of toxicities, dose reduction/interruption is permitted according to protocol. In case of disease progression Sorafenib administration will be discontinued.
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Other Intervention Name(s)
Nexavar
Intervention Description
Sorafenib will be orally administered at a daily dose of 400 mg taken twice daily without food, at least one hour before or two hours after eating. Four weeks of treatments will be considered as a cycle. Each patient enrolled in the study will received medications for topical therapy. Dermatological medications will be provided free. In case of toxicities, dose reduction/interruption is permitted according to the protocol. In case of disease progression Sorafenib administration will be discontinued.
Primary Outcome Measure Information:
Title
The primary aim of this trial is the evaluation of the efficacy of a patient education program in the reduction of HFSR
Description
The primary aim is to determine the efficacy of the patient education program in reducing the incidence of HFSR(all grades).The efficacy is measured in terms of percentage of HFSR-free.Simon's methods will be used to calculate sample size(Simon R,1989).Considering the optimal two-stage design for phase II,considering a difference p1-p0=20% and fixing error probabilities(alfa=0.05 and beta=0.20),the number of patients for the first step is 16.The trial will be terminated if less than 7 HFSR-free patients will be seen.Otherwise the accrual will continue up to a total of 46 patients.
Time Frame
From enrollment in the study until 1 year
Secondary Outcome Measure Information:
Title
Frequency of dose discontinuation, interruption and reduction
Description
Frequency of dose discontinuation, interruption and reduction
Time Frame
From enrollment in the study until 1 year
Title
Incidence of any grade diarrhoea, and other adverse events
Description
Incidence of any grade diarrhoea, and other adverse events
Time Frame
From enrollment in the study until 1 year
Title
Overall Response Rate
Description
Overall Response Rate according to the RECIST criteria
Time Frame
From enrollment in the study until 1 year
Title
Progression free survival (PFR)
Description
Progression free survival (PFR) in study population and comparison of Progression Free Survival (PFS) between age sub groups in the current study population
Time Frame
From enrollment in the study until 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Nephrectomized, metastatic Clear Cell RCC patients not suitable for cytokines or anti-angiogenesis (bevacizumab or sunitinib) therapy as first line treatment Age ≥ 65years ECOG Performance Status of ≤ 2 MSKCC prognostic score, good or intermediate Life expectancy of at least 12 weeks. Subjects with at least one uni-dimensional (for RECIST) measurable lesion. Lesions must be measured by CT/MRI-scan. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of therapy: Hemoglobin > 9.0 g/dl Absolute neutrophil count (ANC) ≥ 1,500/mm3 Platelet count ≥ 100,000/μl Total bilirubin ≤ 1.5 times the upper limit of normal ALT and AST ≤ 2.5 x upper limit of normal (≤ 5 x upper limit of normal for patients with liver involvement of their cancer) Alkaline phosphatase ≤ 4 x upper limit of normal PT-INR/PT ≤ 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.] Serum creatinine ≤ 1.5 x upper limit of normal. Ability to take correctly oral drugs. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. Written Informed Consent To be able to understand medical instruction and to fill in the patient's diary. If not, check if adequately supported by his/her family. Exclusion Criteria: Previous first line treatment for mRCC. No adjuvant or neoadjuvant treatments are allowed. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry) History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring antiarrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension. History of previous or present seizure disorder requiring medication (such as steroids or anti-epileptics), organ allograft, HIV infection or chronic hepatitis B or C Active clinically serious infections (≥ grade 2 NCI-CTC version 3.0) Patients undergoing renal dialysis Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry. Patients with evidence or history of bleeding diathesis Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study Known allergy to sorafenib or one of its constituents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lucia Fratino, oncologist
Organizational Affiliation
Centro di Riferimento Oncologico - IRCCS - Aviano
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centro di Riferimento Oncologico
City
Aviano
State/Province
Pordenone
ZIP/Postal Code
33081
Country
Italy

12. IPD Sharing Statement

Links:
URL
http://www.cro.sanita.fvg.it/
Description
web site of Centro di Riferimento Oncologico (sponsor and coordinator center)

Learn more about this trial

Sorafenib in Elderly Patients With Metastatic Renal Cell Carcinoma

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