Clinical trial NCT00618982: Sorafenib Dose Escalation in Renal Cell Carcinoma
Official title: A Phase II, Multi-centre, Open-label Study to Assess the Efficacy, Safety, Tolerability and Pharmacokinetics of Intrapatient Dose Escalation of Sorafenib as First Line Treatment for Metastatic Renal Cell Carcinoma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Renal Cell
Keywords: Kidney cancer,
Sorafenib,
Dose escalation,
No previous treatment
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2008-02-20
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Sorafenib is a new drug, which is approved under the brand name Nexavar for the treatment of advanced kidney cancer. It is also currently being tested in various other cancers. Sorafenib works by stopping the development of new cancer cells and new blood vessels. By stopping the growth of new blood vessels around a tumor, it is believed that sorafenib prevents the growth of kidney cancer tumors.

This is an "open-label" study which means that the patient, the doctor and Bayer Healthcare will know what tablets the patient is taking. All patients in this study will receive sorafenib tablets. Sorafenib is taken orally as a tablet (two tablets are taken twice a day). Treatment with sorafenib will continue until the patient's tumor grows larger or spreads further or if the patient has intolerable side effects. The dose of sorafenib that the patient will receive in the study will increase at certain points during the patient's treatment, as long as the patient is not experiencing side effects and the patient's tumor has not grown.

Detailed description: Issues on Outcome Measure "Safety and tolerability" will be addressed in the Adverse Events section.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years.
* Metastatic clear cell RCC (renal cell carcinoma)
* Subjects with at least one uni-dimensional measurable lesion.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Memorial Sloan Kettering Cancer Center (MSKCC) good or intermediate category
* Life expectancy of at least 12 weeks.
* Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to treatment
* Signed informed consent must be obtained prior to any study specific procedures.
* Subjects must have received no prior systemic anticancer therapy for the treatment of their renal cell carcinoma
* Prior total nephrectomy

Exclusion Criteria:

* History of cardiac disease
* History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
* Active clinically serious infections (\> grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] version 3.0)
* Symptomatic metastatic brain or meningeal tumors unless the subject is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry.
* Subjects with evidence or history of bleeding diathesis
* Deep vein thrombosis and/or pulmonary embolus within 12 months of the start of treatment.
* Delayed healing of wounds, ulcers or bone fractures
* Subjects with pre-existing thyroid abnormality whose thyroid function cannot be maintained within the normal range by medication
* Subjects undergoing renal dialysis
* Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to 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 and three months after the completion of trial.
* Prior adjuvant sorafenib is excluded.
* Radiotherapy during study or within 3 weeks of start of study drug
* Major surgery within 4 weeks of start of study
* Investigational drug therapy outside of this trial during or within 4 weeks of study entry

Primary outcomes:
measure: Best Response - mITT (Modified Intent-to-treat) Population
timeFrame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
measure: Tumor Response - ITT (Intent to Treat) Population
timeFrame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Secondary outcomes:
measure: Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss)
timeFrame: Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8 and 10 hours post-dose.
measure: Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss)
timeFrame: Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose.
measure: Pharmacokinetics (PK) Analysis - Maximum Observed Concentration in Plasma (Cmax)
timeFrame: Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose.
measure: Pharmacokinetics (PK) Analysis - Time to Maximum Concentration (Tmax)
timeFrame: Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose.
measure: Progression-free Survival (PFS)
timeFrame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
measure: Time to Progression (TTP)
timeFrame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Other outcomes:
measure: Tumor Response - mITT Population
timeFrame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
measure: Disease Control - mITT Population
timeFrame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Locations:
city: Bordeaux
country: France
city: La Roche Sur Yon
country: France
city: Marseille
country: France
city: Nantes
country: France
city: Paris Cedex 10
country: France
city: Tours
country: France
city: Tübingen
country: Germany
state: Baden-Württemberg
city: Marburg
country: Germany
state: Hessen
city: Hannover
country: Germany
state: Niedersachsen
city: Mainz
country: Germany
state: Rheinland-Pfalz
city: Jena
country: Germany
state: Thüringen
city: Aviano
country: Italy
state: Pordenone
city: Milano
country: Italy
city: Pavia
country: Italy
city: Olsztyn
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Greater Manchester
country: United Kingdom
state: Manchester
city: Cardiff
country: United Kingdom
state: South Glamorgan
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: