Clinical trial NCT00117637: BAY43-9006 (Sorafenib) Versus Interferon Alpha-2a in Patients With Unresectable and/or Metastatic Renal Cell Carcinoma
Official title: A Randomised, Open-label, Multi-centre Phase II Study of BAY43-9006 (Sorafenib) Versus Standard Treatment With Interferon Alpha-2a in Patients With Unresectable and/or Metastatic Renal Cell Carcinoma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Renal Cell
Keywords: Renal Cell Cancer
RCC
Cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2005-07-08
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to:

* Find out if patients receiving BAY43-9006 will live longer without tumor progression than those receiving standard therapy with interferon alpha-2a
* Find out if a higher dose of BAY43-9006 can inhibit tumor progression in patients who progressed during standard dose treatment with BAY43-9006, and for how long these patients live without progression
* Find out how long patients live without progression who receive BAY43-9006 after failing to respond to standard therapy with interferon alpha-2a
* Find out in how many percent of patients BAY43-9006 prevents the growth of or shrinks kidney tumors and/or their metastases depending on treatment and dosage
* Find out if BAY43-9006 has any effect on the quality of life of patients with kidney cancer
* Find out the level of BAY43-9006 in the blood once per month and any changes in this level
* Find out whether BAY43-9006 effects are associated with specific biomarkers

Detailed description: Analyses on Biomarkers were exploratory and assessed as tertiary objective of the trial.

Eligibility criteria: Inclusion Criteria:

* Patients who give written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
* Male or female patients \>= 18 years of age
* Patients who have a life expectancy of at least 12 weeks
* Patients, who suffer from unresectable and/or metastatic, measurable predominantly clear cell RCC (Renal Cell Carcinoma) histologically or cytologically documented
* Patients must have undergone prior (at the time of primary diagnosis) complete surgical excision of primary RCC tumor
* Patients must have had no prior systemic therapy for advanced RCC. Prior systemic therapy is defined as any treatment with a chemotherapy agent (or regimen), an immunotherapy agent (or regimen) or an investigational treatment agent (or regimen) against the renal cell carcinoma. Megestrol acetate or medroxyprogesterone will constitute as a prior systemic therapy
* Patients who have at least one uni-dimensional measurable lesion by CT (Computed tomography)-scan or MRI (Magnetic resonance imaging) according to Response Evaluation Criteria in Solid Tumors (RECIST)
* Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1
* Adequate bone marrow, liver , and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening
* Hemoglobin \>9.0 g/l
* Absolute neutrophil count ( ANC)\>1,500/mm3
* Platelets\> or = 100,000/ul
* Total bilirubin \< 1.5 x the upper limit of normal
* ALT (Alanine aminotransferase) and AST (Aspartate aminotransferase) \< 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
* PT (Prothrombin Time) or INR (International Normalized Ratio) and PTT (Partial Thromboplastin Time) \< 1.5 x upper limit of normal (patients who receive anti-coagulation treatment with an agent such as warfarin or heparin will be allowed to participate. For patients on warfarin, close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at pre dose, as defined by the local standard of care)

Exclusion Criteria:

* 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 \[Noninvasive papillary carcinoma\], Tis \[Carcinoma in situ: "flat tumor"\]\&T1 \[Tumor invades subepithelial connective tissue\]) or any cancer curatively treated \> 5 years prior to study entry
* Complete renal shut-down requiring hemo- or peritoneal dialysis
* History of cardiac disease : congestive heart failure \> NYHA (New York Heart Association) class 2: active cardiovascular disease( MI (Distant metastasis) more than 6 months prior to study entry is allowed); cardiac arrhythmia requiring anti-arrythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
* Active clinically serious bacterial or fungal infections (\>= grade 2 NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events), Version 3)
* Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
* 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 this brain tumour site at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies (head CT or MRI at screening always required)
* Patients with seizure disorder requiring medication (such as steroid anti-epileptics)
* 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
* Known or suspected allergy to the investigational agent or any agent given in association with this trial
* Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study
* Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial

Primary outcomes:
measure: Progression-free Survival (PFS) Based on Independent Radiological Review for the First Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Secondary outcomes:
measure: Progression-free Survival (PFS) Based on Investigator Assessment for the First Intervention Period
timeFrame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
measure: Disease Control (DC) According to Independent Central Review for the First Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Disease Control (DC) According to the Investigator Assessment for the First Intervention Period
timeFrame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
measure: Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period
timeFrame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
measure: Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) After Intervention for the First Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the First Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the First Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the Second Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Tumor Response According to the Independent Radiological Review for the First Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Tumor Response According to the Investigator Assessment for the First Intervention Period
timeFrame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
measure: Tumor Response According to the Investigator Assessment for the Second Intervention Period
timeFrame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
measure: Progression Free Survival According to the Investigator Assessment (Second Intervention Period)
timeFrame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
measure: Overall Survival (OS)
timeFrame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
measure: Slope - Change in Trough Concentration/Cycle
timeFrame: From start of treatment of the first subject until 15 months later assessed every 4 weeks.
measure: Average of All Trough Plasma Concentrations
timeFrame: From start of treatment of the first subject until 15 months later assessed every 4 weeks.
measure: Duration of Response According to the Independent Radiological Review for the First Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Duration of Response According to the Investigator Assessment for the First Intervention Period
timeFrame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
measure: Duration of Response According to the Investigator Assessment for the Second Intervention Period
timeFrame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
measure: Time to Response According to the Independent Radiological Review for the First Intervention Period
timeFrame: From randomization of the first subject until 15 months later, assessed every 8 weeks
measure: Time to Response According to the Investigator Assessment for the First Intervention Period
timeFrame: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
measure: Time to Response According to the Investigator Assessment for the Second Intervention Period
timeFrame: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
measure: Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period
timeFrame: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
measure: Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period
timeFrame: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
Other outcomes:
Locations:
city: Sacramento
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Chicago
country: United States
state: Illinois
city: Frederick
country: United States
state: Maryland
city: Las Vegas
country: United States
state: Nevada
city: Cleveland
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Dallas
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Bordeaux
country: France
city: Lille Cedex
country: France
city: Lyon Cedex
country: France
city: Marseille
country: France
city: Nantes
country: France
city: Paris Cedex 15
country: France
city: Toulouse
country: France
city: Villejuif
country: France
city: Ulm
country: Germany
state: Baden-Württemberg
city: München
country: Germany
state: Bayern
city: Frankfurt
country: Germany
state: Hessen
city: Düsseldorf
country: Germany
state: Nordrhein-Westfalen
city: Mainz
country: Germany
state: Rheinland-Pfalz
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Poznan
country: Poland
city: Szczecin
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Kazan
country: Russian Federation
city: Kirov
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Donetsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kiev
country: Ukraine
city: Lviv
country: Ukraine
city: Sutton
country: United Kingdom
state: Surrey
city: London
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Escudier B, Szczylik C, Hutson TE, Demkow T, Staehler M, Rolland F, Negrier S, Laferriere N, Scheuring UJ, Cella D, Shah S, Bukowski RM. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Mar 10;27(8):1280-9. doi: 10.1200/JCO.2008.19.3342. Epub 2009 Jan 26.