A Multi-Center, Non-Controlled Clinical Study of Sorafenib Adjuvant Therapy in Advanced Renal-Cell Carcinoma (AGuo)

A Multi-Center, Non-Controlled Clinical Study of Sorafenib Adjuvant Therapy in Locally Advanced Renal-Cell Carcinoma After Radical Nephrectomy

A one-arm,open,multi-center study, to evaluate sorafenib (400mg twice daily ) as a adjuvant to prevent recurrence of RCC(renal cell carcinoma) patients after radical nephrectomy with a high-risk of recurring. To observe disease-free survival and the survival rate in 3 years,5 years.

The purpose of this study is:

• To study the efficacy of Sorafenib as an adjuvant therapy for reducing recurrence rate in locally advanced renal-cell carcinoma (RCC) after radical nephrectomy.
• To observe the incidence of hand-foot skin reaction (HFSR) after the Urea (10% or 5%) based cream intervention treatment.

The primary end point is the disease-free survival(DFS).The secondary end point is overall survival(OS),the drug safety and tolerance, the occurrence of hand foot skin reaction(HFSR) at the week of 3,6,12,the skin toxicity(not include HFSR) higher than CTCAE(Common Terminology Criteria for Adverse Events) Grade 2 at the 12th week, the incidence of HFSR after the Urea (10% or 5%) based cream intervention treatment.

Study Overview

• Status: Unknown
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: sorafenib

Detailed Description

A one-arm, open, multi-center study, to evaluate sorafenib (400mg twice daily) as a adjuvant to prevent recurrence of RCC(renal cell carcinoma) patients after radical nephrectomy with a high-risk of recurring. To observe disease-free survival and the survival rate in 3 years, and 5 years. To observe the incidence of hand-foot skin reaction (HFSR) after the Urea (10% or 5%) based cream intervention treatment. 140 subjects are prospected to enter the trial.

The sorafenib adjuvant therapy is unremitting with a time of 12 months. For a convenient record, every 6 weeks is regarded as a single observational cycle. The end-point are recurrence, not being tolerant to the toxicity, need to stop the intervening study or withdrawing the informed consent. It is necessary to evaluate the efficacy and safety every 6 weeks. At the screening stage and every 12 weeks imaging review are performed such as abdominal and chest CT or MRI, the imaging methods of a single subject should be in uniformity during the trial.

The post-treatment evaluation are performed 30 days after the last usage of the adjuvant in order to collect all the adverse events (AE) and the survival rates of all the subjects. The agent-relevant AE (known or unknown) should be reported to the drug safety institution, the patients should be visited until the events solved, except the events can not be solved for the subjects' underlying diseases.

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Jianhui Ma
      • Contact: Jianhui Ma Jianhui Ma Jianhui Ma, Doctor; Phone Number: 01086108878

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Preoperative Criteria

• Renal local advanced renal cell carcinoma and be suitable to radical nephrectomy.
• Tumor >=7cm, the lymph nodes in metastasis can be resectable, the renal vein or inferior caval vein with metastatic thrombus can be resectable also, clinical staging>=T2anyNMo.
• Resectable tumor with multiple-lesion in ipsolateral kidney Enrolment Criteria
• No distant metastasis.
• Not undergoing any adjuvant or systematic anti-tumor therapy, such as chemotherapy, biotherapy or radiotherapy.
• After the nephrectomy 4-12 weeks and should be recovery in the postoperative complications.
• ECOG scores 0-1.
• Referring to the Scoring Algorithm to Predict Metastasis after Radical Nephrectomy in Patients with clear cell renal cell carcinoma, all the patients score higher than 6. Metastatic lymph node with clinical diagnosis have been resected, all the resected specimen edge be negative in pathological detection.

The pathological diagnosis of renal cell carcinoma:

• No remnant tumor with postoperative imaging screening with CT or MRI.

• The liver and renal function, hemocytogenesis function meet the below criteria within the 4 weeks before the enrollment.

  • Granulocytes count >1500/mm3
  • Blood platelet >100000/mm3
  • Creatinine<2 times of the upper of the reference value
  • Total bilirubin<1.5 times of the upper of the reference value
  • Alanine aminotransferase/aspartate aminotransferase<2.5 times of the upper of the reference value
  • The informed consent has been endorsed.

Exclusion Criteria:

• Other coincident carcinoma, but not including carcinoma in situ of cervix and basal cell epithelioma after radical therapy and bladder carcinoma superficially(Ta,Tis,T1) or carcinoma having been cured 3 years ago.
• Cardiac dysrhythmia need agent intervention(not including β-receptor inhibitive or digoxin treatment), coronary heart disease, myocardial infarction occurred in the later 6 months, heart failure assessment higher than NYHA II
• Seriously active infection with bacteria or fungus
• HIV infection or HBV/HCV infection with IFN-a intervention.
• Dysfunction in blood coagulation.
• Epilepsia with drug treatment.
• Those cannot take tablets orally.
• Allogeneic organ transplantation.
• Drug abuse or concomitant conditions such as psychologically or socially factors which may intervene the assessment.
• Hypersensitiveness to the studying adjuvant or the trial-relevant drugs.
• Pregnancy or lactation, pregnancy test must be negative within the 14 days before the trial beginning, either females or males must be contraceptive during the trial.

• The following concomitant therapeutics must be excluded:

  • Anti-tumor agents, immunological or hormonal therapy
  • Radiotherapy
  • Biological therapeutics such as G-CSF or GM-CSF
  • Autologous bone marrow transplantation or stem cell treatment
  • The other trial medicine therapeutics
  • Bevacizumab treatment or other agents effected in VEGF or VEGF-receptor, such as inhibitive in Raf or MEK

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sorafenib; To study the efficacy of Sorafenib as an adjuvant therapy for reducing recurrence rate in locally advanced renal-cell carcinoma (RCC) after radical nephrectomy.	Drug: sorafenib; sorafenib 400mg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
disease free survival	November 2008-November 2013

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	November 2008-November 2013

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Collaborators: China Medical University, China; Changhai Hospital; Fudan University; Peking Union Medical College Hospital; Huazhong University of Science and Technology; Shanghai Jiao Tong University School of Medicine; Central South University; Zhejiang University; Tianjin Medical University; Jiangsu Province Centers for Disease Control and Prevention; Sichuan University; Beijing University of Chinese Medicine

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Anticipated): November 1, 2011
• Study Completion (Anticipated): November 1, 2013

Study Registration Dates

• First Submitted: December 30, 2009
• First Submitted That Met QC Criteria: December 30, 2009
• First Posted (Estimate): December 31, 2009

Study Record Updates

• Last Update Posted (Estimate): January 6, 2010
• Last Update Submitted That Met QC Criteria: January 5, 2010
• Last Verified: August 1, 2008

More Information

Terms related to this study

• Keywords: renal cell carcinoma; sorafenib; disease free survival; Hand food skin reaction
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: Bay 43-9006