Study to Determine the Safety, Maximum Tolerated Dose, Pharmacokinetics of Sorafenib (BAY43-9006)

MTD was determined by testing increasing doses up to 400 mg twice daily (bid) on dose escalation cohorts 1 to 3 with 3 patients each. MTD reflects highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity (DLT) in more than 30% of patients; e.g., hematologic toxicities like Common Toxicity Criteria (CTC) Grade 4 Neutropenia in specific conditions, platelets \< 25,000 cells/mL; specific non-hematologic/biochemical toxicities CTC Grade 3 or 4; additionally, any toxicity considered by the investigator severe enough was designated a DLT); CTC Version 2 were used.

Time frame: 21 days

Population: All subjects who received at least 1 dose of any study drug treatment were included in the Intent-To-Treat/safety populations. Efficacy parameters of time to death, time to progression, and response rate (confirmed partial response \[PR\] plus complete response \[CR\]) were determined for this population.

Participants are considered at risk for toxicity if participants had a lab measurement for the toxicity \>= National Cancer Institute Common Toxicity Criteria (NCI CTC) Grade 3 as defined by the NCI CTC version 2; SGOT: Serum Glutamic-Oxaloacetic Transaminase, SGPT: Serum Glutamic-Pyruvic Transaminase, AST: Aspartate Aminotransferase, ALT: Alanine Aminotransferase.

Time frame: Start of treatment until death or within 14 days last study drug intake

Population: The Intent-To-Treat (ITT) population included subjects who received at least one dose of sorafenib or chemotherapy and had at least one post baseline assessment. Efficacy analyses were performed on the ITT population.

The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. A plot of concentration vs time after dosing is created, and the area under this curve is calculated by standard methods (eg, trapezoidal rule) to provide a measure of how much drug was in the bloodstream following dosing.

Time frame: At day 2 in study

Population: subjects with valid pharmacokinetics (PK) profiles

Cmax refers to the highest plasma concentration of drug reached after dosing. It is obtained by collecting a series of blood samples after dosing, and analyzing them for drug content by a sensitive and specific analytical method. The highest measured concentration is referred to as the Cmax.

Time frame: At day 2 in study

Population: subjects with valid PK profiles

Tmax refers to the time after dosing when a drug attains its maximum concentration in the blood. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. The time corresponding to the highest measurable concentration (Cmax) is referred to as Tmax.

Time frame: At day 2 in study

Population: subjects with valid PK profiles

Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.

Time frame: From start of treatment until progression or death occurs assessed every 6 weeks.

Population: The Intent-To-Treat (ITT) population included subjects who received at least one dose of sorafenib or chemotherapy and had at least one post baseline assessment. Efficacy analyses were performed on the ITT population

Frequency Threshold for reporting Other Adverse Events: 5%. The responses reported in these participants were from start of treatment until 18 Sep 2008.

Time frame: From start of treatment until 18 Sep 2008, up to 6 years

Population: 25 of 119 participants from the Expansion Phase, were still on the treatment as of 31 May 2005. Of these, 6 subjects were continuing to receive sorafenib in combination with carboplatin and/or paclitaxel and 19 subjects were receiving single-agent sorafenib.

The responses reported in these participants were from start of treatment until 18 Sep 2008.

Time frame: From start of treatment until 18 Sep 2008, up to 6 years

Population: 25 of 119 participants from the Expansion Phase, were still on the treatment as of 31 May 2005. Of these, 6 subjects were continuing to receive sorafenib in combination with carboplatin and/or paclitaxel and 19 subjects were receiving single-agent sorafenib.