Clinical Trial on the Mixture of G, C and S in Treatment of Patients With RCC

Study Overview
=================
Brief Summary
-----------------
Main Objective: To evaluate progression-free survival in patients with unresectable renal cell carcinoma (RCC) treated with a combination of gemcitabine, capecitabine, and sorafenib.

Official Title
-----------------
Phase II Clinical Trial, Non-Randomized, Multicentre, on the Combination of Gemcitabine, Capecitabine and Sorafenib (Bay 43-9006) in Treatment of Patients With Unresectable and/or Metastatic Renal Cell Carcinoma (RCC)

Conditions
-----------------
Carcinoma, Renal Cell

Intervention / Treatment
-----------------
* Drug: Gemcitabine, Capecitabine and Sorafenib (6 cycles)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must give their written informed consent before any procedure related to the study is performed; therefore, it must be given at the selection visit. The patient must be informed that he has the right to withdraw from the study at any time, without any kind of prejudice. Patients with renal clear cell carcinoma (RCC), unresectable and/or metastatic, histologically or cytologically documented (excluding the less common subtypes). Patients must not be candidates for any immunotherapeutic treatment, according to the response predictive factors, or must be intolerant to immunotherapeutic treatment. Patients classified as having median or low risk, according to Motzer's scoring. Patients (men or women) with ages equal or superior to 18 years old. ECOG ≤ 1. Assessable or measurable disease. Patients with adequate haematological function, defined as: Neutrophils ≥ 1.5 x 10^9/L Blood platelets ≥ 100 x 10^9/L Haemoglobin ≥ 10 g/dl Patients with adequate hepatic, renal, medullar and coagulation function, according to the following criteria: Total bilirubin < 1.5 times the superior limit of normality ALT and AST < 2.5 times the superior limit of normality (< 5 times the superior limit of normality in case of liver failure due to cancer) Amylase and lipase < 1.5 times the superior limit of normality Serum creatinine < 2 times the superior limit of normality TP or INR and TTP < 1.5 times the superior limit of normality. If patient is receiving anticoagulants, strict monitoring will be carried out, with evaluations on a weekly basis, at least, until the INR is stable, referring to a determination previous to dose administration, according to local standard care. Patients with a life expectancy superior to 12 weeks, at least. Patients may have received radiotherapy; however, this must not be the only target lesion. Patients from both sexes must use adequate contraceptive methods (oral or injectable contraceptives, intrauterine device, condom, sterilization) whilst participating in the protocol. After the retreat of treatment with BAY 43-9006, the contraceptive methods must be used for 4 weeks in women and for 3 months in men. Patients who are capable of accomplishing the study's requirements and without any impediments to follow the instructions while on study Exclusion Criteria: Patients who do not give their written informed consent to participate in the study. Patients with less common RCC subtypes, such as pure papillary cell tumours, Bellini carcinoma, medullary carcinoma or the oncocytic chromophobes and sarcomatoid variants, will be excluded from the study. Patients that have received previous treatment with chemotherapy or that had tumours that evolved during or after immunotherapy treatment. Patients that, due to their characteristics, may obtain a potential benefit from immunotherapy treatment. Patients that have received previous anti-angiogenic treatment. High-risk patients according to Motzer's classification. Concomitant treatment with another chemotherapy or immunotherapy. Arterial uncontrolled hypertension, which is defined as a systolic arterial pressure value > 150 mmHg or diastolic arterial pressure value > 90 mmHg, despite adequate medical treatment. Patients with a primary cancer diagnosis different from RCC, except in situ cervical carcinoma, baseline cellular carcinomas or superficial bladder tumours, prostate cancer pT1 gleason < 6 or other malign tumours which have received curative treatment > 5 years previous to the inclusion in this study. Cardiac arrhythmia antecedents, that require treatment with anti-arrhythmics (except for beta-blockers or digoxin), symptomatic coronary disease or ischemia (myocardial infarction in the previous 6 months) or congestive cardiac insufficiency > New York Heart Association (NYHA) class II Patients with active bacterial or fungal infectious processes, which are considered severe from the clinical point of view (≥ Common Terminology Criteria from the National Cancer Institute [CTC from NCI] grade 2, version 3) Patients that present previously known positive serology for HIV or chronic hepatitis B or C. Antecedents of organ allograft. Meningeal carcinomatosis or symptomatic uncontrolled cerebral disease. Patients with epileptic disorders that require medication (such as antiepileptics). All unstable conditions that could put the patient's security and/or his study accomplishment in danger. Abuse of substances, clinical conditions, psychological or social, that may interfere with the patient's participation in the study or with the evaluation of the study's results. Patients that present any contraindication or allergy to the study's investigational product. Patients that are participating or that have participated in any clinical trial in the 4 weeks previous to inclusion. Pregnant or breastfeeding women. Women of fertile age must have a negative result in the pregnancy test performed 7 days before the beginning of the administration of the study medication. Both men and women included in the study must use an adequate contraceptive method.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Gemcitabine, Capecitabine and Sorafenib (6 cycles)|Gemcitabine: 1000 mg/m2 i.v. days 1 and 8. Capecitabine: 650 mg/m2 i.v. day 1 to 14. (change to 500mg/m2 after amendment nº2 (dated on 10/10/2007) Sorafenib:400 mg/12h v.o. day 1 to 21|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | every 3 cycles and every two months in patients with sorafenib administered as monotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| security profile |  | every 3 cycles and every two months in patients with sorafenib administered as monotherapy | 
| Objective response index (CR/PR) and tumor growth control (CR/PR/SD) |  | every three cycles and every two months in patients with Sorafenib treated as single agent | 
| Duration of response |  | every three cycles and every two months in patients with Sorafenib treated as single agent | 
| Global survival |  | At last contact date or death date | 
| Time to progression |  | every three cycles and every two months in patients with Sorafenib treated as single agent | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
renal, sorafenib, Unresectable and/or metastatic renal cell cancer