Phase I Study to Determine the Safety, Maximum Tolerated Dose, PK of BAY43-9006 in Repeated Cycles of 18 Days On/3 Days Off in Combination With Paclitaxel and Carboplatin Chemotherapy in Patients With Advanced, Refractory Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Sorafenib 100 mg (50-mg tablet)
- Conditions
- Carcinoma
- Sponsor
- Bayer
- Enrollment
- 158
- Primary Endpoint
- Maximum Tolerated Dose (MTD) of Sorafenib in Combination With Paclitaxel and Carboplatin
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The primary objective of the study was to define the safety profile and maximum tolerated dose (MTD) of sorafenib tablets in combination with carboplatin and paclitaxel chemotherapy in patients with advanced, refractory solid tumors.
The secondary objectives were evaluation of pharmacokinetics (PK) and tumor response of these patients being treated with sorafenib in combination with paclitaxel and carboplatin.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed solid tumors
- •Evaluable disease
- •Eastern Cooperative Oncology Group (ECOG) 0 or 1
- •Life expectancy minimum 12 weeks
Exclusion Criteria
- •Congestive heart failure
- •Serious arrhythmias
- •Coronary artery disease (CAD) or ischemia
- •HIV (human immunodeficiency virus)
- •Hepatitis B or C
- •Serious active infection
- •Metastatic brain or meningeal tumors
Arms & Interventions
Sorafenib 100 mg (50-mg tablet)
Dose-escalation cohort 1: Sorafenib (Nexavar, BAY43-9006) 100 mg twice daily (50-mg tablet). Treatment were planned until primary completion date (PCD).
Intervention: Sorafenib 100 mg (50-mg tablet)
Sorafenib 200 mg (50-mg tablet)
Dose-escalation cohort 2: Sorafenib (Nexavar, BAY43-9006) 200 mg twice daily (50-mg tablet). Treatment were planned until primary completion date (PCD).
Intervention: Sorafenib 200 mg (50-mg tablet)
Sorafenib 400 mg (50-mg tablet)
Dose-escalation cohort 3: Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (50-mg tablet). Treatment were planned until primary completion date (PCD).
Intervention: Sorafenib 400 mg (50-mg tablet)
Sorafenib 400 mg (200-mg tablet)
Dose-escalation cohort 4: Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (200-mg tablet). Treatment were planned until primary completion date (PCD).
Intervention: Sorafenib 400 mg (200-mg tablet)
Sorafenib 400 mg (Expansion)
Dose-expansion cohort: Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (200-mg tablet) expansion. Treatment were planned until primary completion date (PCD). 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 until 18 Sep 2008.
Intervention: Sorafenib 400 mg (Expansion)
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD) of Sorafenib in Combination With Paclitaxel and Carboplatin
Time Frame: 21 days
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.
Participants With Hematological and Biochemical Toxicities
Time Frame: Start of treatment until death or within 14 days last study drug intake
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.
Secondary Outcomes
- Maximum Concentration (CMAX) Start From Day 2 of Cycle 1(At day 2 in study)
- Time of Maximum Concentration (TMAX) Start From Day 2 of Cycle 1(At day 2 in study)
- Area Under the Curve From Time 0 to 12 Hours Post-dose (AUC 0-12) Start From Day 2 of Cycle 1(At day 2 in study)
- Tumor Response(From start of treatment until progression or death occurs assessed every 6 weeks.)