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

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)

Main Objective:

To evaluate progression-free survival in patients with unresectable renal cell carcinoma (RCC) treated with a combination of gemcitabine, capecitabine, and sorafenib.

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.