Phase III Study of Sorafenib in Patients With Renal Cell Carcinoma (RCC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00586105
First received: December 21, 2007
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

A multicenter uncontrolled study of sorafenib in patients with unresectable and/or metastatic renal cell carcinoma (RCC) to assess the pharmacokinetic profile, safety and tolerability, and efficacy.


Condition Intervention Phase
Carcinoma, Renal Cell
Drug: Sorafenib (Nexavar, BAY43-9006)
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Uncontrolled Study of Sorafenib in Patients With Unresectable and/or Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Pharmacokinetics Measured as Area Under Curve (AUC[0-12h]) [ Time Frame: 12 hours after at least 21 days of uninterrupted dosing ] [ Designated as safety issue: No ]
    The AUC(0-12h) was the observed AUC, calculated using a combination of linear and log trapezoidal rules, from pre-dose to 12 hours post-dose. The normalized AUC (AUC norm) is AUC (0-12h) divided by (dose [mg]/weight [kg]).

  • Pharmacokinetics Measured as Concentration (Cmax at Tmax and Cmin at Tmin) [ Time Frame: 12 hours after at least 21 days of uninterrupted dosing ] [ Designated as safety issue: No ]
    Cmax (maximum concentration) was measured at the time point at which the maximum concentration (Tmax) was observed. Cmin (minimum concentration) was measured at the time point at which the minimum concentration (Tmin) was observed.

  • Pharmacokinetics Measured as Concentration (Cmax Normalized at Tmax and Cmin Normalized at Tmin) [ Time Frame: 12 hours after at least 21 days of uninterrupted dosing ] [ Designated as safety issue: No ]
    Cmax (maximum concentration) was measured at the time point at which the maximum concentration (Tmax) was observed. Cmin (minimum concentration) was measured at the time point at which the minimum concentration (Tmin) was observed. The normalized variables (Cmax norm and Cmin norm) are the variables (Cmax and Cmin, see Primary Outcome Measure 2) divided by [dose (mg)/weight (kg)].


Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Number of days from date of first dose of study drug to date first observed disease progression or death (whichever was earlier) was documented up to 17.25 months ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) was defined as the time from the date of receipt of first dose of study drug to disease progression, radiological or clinical, or death, whichever was earlier. Subjects still alive without tumor progression at the time of analysis were censored at their date of last tumor evaluation.

  • Overall Survival (OS) [ Time Frame: Time from start of therapy to death up to 17.25 months ] [ Designated as safety issue: No ]
    Overall survival (OS) was measured from the date of first dose of study drug until the date of death due to any cause. Survival time for subjects still alive at the time of analysis was censored at the date of last contact.

  • Time to Progression (TTP) [ Time Frame: Time from start of study medication to clinical or radiological disease progression which ever occurs first up to 17.25 months ] [ Designated as safety issue: No ]
    Time to progression (TTP) was defined as the time from date of receipt of first dose of study drug to disease progression, radiological or clinical. Subjects without tumor progression at the time of analysis were censored at their last date of tumor evaluation.

  • Disease Control (DC) [ Time Frame: From start to end of study medication up to 17.25 months ] [ Designated as safety issue: No ]
    The DC was defined as subjects who had a best response rating of complete response (CR), partial response (PR), or stable disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST) that was maintained for at least 28 days from the first demonstration of that rating. CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target). PR: at least a 30% decrease in the sum of longest diameters (LD) of target lesions taking as reference the baseline sum LD. SD: steady state of disease; do not qualify for PR or progressive disease (PD).

  • Overall Best Response [ Time Frame: Best response observed from start to end of study medication up to 17.25 months ] [ Designated as safety issue: No ]
    The best overall response was defined as the number of subjects with a confirmed CR, PR, SD, or PD. Tumor response was evaluated using RECIST. PD: at least a 20% increase in the sum of LD of measured lesions taking as ref. the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Appearance of new lesions will also constitute PD. In exceptional circumstances, unequivocal progression of a non-measured lesion may be accepted as evidence of disease progression.

  • Overall Response Duration [ Time Frame: From PR or CR to progression or death up to 17.25 months ] [ Designated as safety issue: No ]
    Overall response duration was to be calculated for subjects who had a confirmed PR or CR, defined as the time from first assessment showing a PR or CR to progression or death.

  • Time to Objective Response [ Time Frame: Time from start of study medication to first documented PR or CR up to 17.25 months ] [ Designated as safety issue: No ]
    Time to objective response was defined as the time from the date of receipt of first dose of study drug to first assessment showing a confirmed PR or CR.


Enrollment: 39
Study Start Date: December 2005
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib (Nexavar, BAY43-9006)
400 mg (2 tablets of 200 mg) of sorafenib per oral (PO) twice daily (BID)
Drug: Sorafenib (Nexavar, BAY43-9006)
400 mg (2 tablets of 200 mg) of sorafenib per oral (PO) twice daily (BID)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients who have a life expectancy of at least 12 weeks
  • Patients, who suffer from unresectable and/or metastatic, measurable RCC histologically or cytologically documented. Patients with rare subtypes of RCC such as pure papillary cell tumor, mixed tumor containing predominantly sarcomatoid cells, Bellini carcinoma, medullary carcinoma, or chromophobe oncocytic tumors are excluded from study participation.
  • Patients who have received not more than one prior systemic therapy for advanced disease which was completed at least 30 days prior to the first dose of study medication.
  • Patients who have at least one uni-dimensional measurable lesion by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI) according to Response Evaluation Criteria in Solid Tumours (RECIST)
  • Patients with "Intermediate" or "low" risk per the Motzer score
  • Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate bone marrow, liver and renal function at screening as assessed by the following:
  • Total bilirubin < 1.5 x the upper limit of normal.
  • Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer).
  • Amylase and lipase < 1.5 x the upper limit of normal.

    • Serum creatinine < 2.0 x the upper limit of normal.
    • Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT) < 1.5 x upper limit of normal

Exclusion Criteria:

  • Previous or concurrent cancer that is distinct in primary sit or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, adequately treated basal cell carcinoma, superficial bladder tumors [Ta (Noninvasive papillary carcinoma), Tis (Carcinoma in situ: "flat tumor") and T1 (Tumor invades subepithelial connective tissue)] or any cancer curatively treated > 3 years prior to study entry)
  • Patients who completed their prior systemic treatment regimen less than 30 days
  • Cardiac arrhythmias requiring anti-arrhythmic (excluding beta blockers or digoxin), symptomatic coronary artery disease or ischemia
  • Active clinically serious bacterial or fungal infections
  • Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C requiring current interferon treatment
  • Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging studies within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry.
  • Patients with evidence or history of bleeding diathesis.
  • Patients with seizure disorder requiring medication
  • History of organ allograft
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • Pregnant or breast-feeding patients.

Excluded concomitant medications:

  • Concurrent anti-cancer chemotherapy, immunotherapy, or hormonal therapy except Bisphosphonates
  • Radiotherapy during study or within 3 weeks of start of study drug.
  • Biological response modifiers, such as Granulocyte-Colony Stimulating Factor (G-CFS) or Granulocyte macrophage colony-stimulating factor (GM-CFS), within 3 weeks prior to study entry or during study
  • Significant surgery within 4 weeks prior to start of study drug
  • Autologous bone marrow transplant or stem cell rescue within 4 months of study
  • Investigational drug therapy during or within 4 weeks prior to first drug administration and during the study
  • St John's Wort
  • Xiao Chai Hu Tang
  • Prior and concomitant use of Bevacizumab, and all other drugs (investigational or licensed) that target Vascular Endothelial Growth Factor (VEGF)/VEGF-Receptors, Raf-kinase inhibitors (RKI), Methyl Ethyl Ketone (MEK) or Farnesyl transferase inhibitors
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00586105

Locations
China, Jiangsu
Nanjing, Jiangsu, China, 210003
China
Beijing, China, 100021
Shanghai, China, 200127
Shanghai, China, 200032
Taiwan
Tainan, Taiwan, 70428
Taipei, Taiwan, 10002
Taipei, Taiwan, 112
Taoyuan, Taiwan, 333
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00586105     History of Changes
Other Study ID Numbers: 11559
Study First Received: December 21, 2007
Results First Received: February 1, 2010
Last Updated: March 25, 2014
Health Authority: China: Ministry of Health
Taiwan: Department of Health

Keywords provided by Bayer:
Sorafenib
Nexavar
Metastatic RCC
Renal Cell Carcinoma
Unresectable RCC

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014