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

This study has been completed.
Sponsor:
Collaborator:
Onyx Pharmaceuticals
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00941863
First received: June 12, 2009
Last updated: February 24, 2016
Last verified: February 2016

June 12, 2009
February 24, 2016
July 2002
May 2005   (final data collection date for primary outcome measure)
  • Maximum Tolerated Dose (MTD) of Sorafenib in Combination With Paclitaxel and Carboplatin [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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.
  • Determination of maximum tolerated dose of sorafenib in combination with paclitaxel and carboplatin [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • Hematological and biochemical toxicities [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00941863 on ClinicalTrials.gov Archive Site
  • Tumor Response [ Time Frame: From start of treatment until progression or death occurs assessed every 6 weeks. ] [ Designated as safety issue: No ]
    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.
  • Area Under the Curve From Time 0 to 12 Hours Post-dose (AUC 0-12) Start From Day 2 of Cycle 1 [ Time Frame: At day 2 in study ] [ Designated as safety issue: No ]
    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.
  • Maximum Concentration (CMAX) Start From Day 2 of Cycle 1 [ Time Frame: At day 2 in study ] [ Designated as safety issue: No ]
    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 of Maximum Concentration (TMAX) Start From Day 2 of Cycle 1 [ Time Frame: At day 2 in study ] [ Designated as safety issue: No ]
    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.
  • Tumor Response [ Time Frame: Number of days from start of treatment to progression ] [ Designated as safety issue: No ]
  • Evaluation of PK of Sorafenib in patients treated with paclitaxel and carboplatin as measured by area under the curve from time 0 to 12 hours post-dose (AUC 0-12) Day 2 [ Time Frame: At 2 and 19 days in study ] [ Designated as safety issue: No ]
  • Evaluation of PK of Sorafenib in patients treated with paclitaxel and carboplatin as measured by maximum concentration (CMAX) Day 2 [ Time Frame: At 2 and 19 days in study ] [ Designated as safety issue: No ]
  • Evaluation of PK of Sorafenib in patients treated with paclitaxel and carboplatin as measured by time of maximum concentration (TMAX) Day 2 [ Time Frame: At 2 and 19 days in study ] [ Designated as safety issue: No ]
  • Serious Adverse Events [ Time Frame: From start of treatment until 18 Sep 2008, up to 6 years ] [ Designated as safety issue: Yes ]
    The responses reported in these participants were from start of treatment until 18 Sep 2008.
  • Other Adverse Events [ Time Frame: From start of treatment until 18 Sep 2008, up to 6 years ] [ Designated as safety issue: Yes ]
    Frequency Threshold for reporting Other Adverse Events: 5%. The responses reported in these participants were from start of treatment until 18 Sep 2008.
Not Provided
 
Study to Determine the Safety, Maximum Tolerated Dose, Pharmacokinetics of Sorafenib (BAY43-9006)
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

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Carcinoma
  • Drug: Sorafenib 100 mg (50-mg tablet)
    Sorafenib (Nexavar, BAY43-9006) 100 mg twice daily (50-mg tablet)
  • Drug: Sorafenib 200 mg (50-mg tablet)
    Sorafenib (Nexavar, BAY43-9006) 200 mg twice daily (50-mg tablet)
  • Drug: Sorafenib 400 mg (50-mg tablet)
    Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (50-mg tablet)
  • Drug: Sorafenib 400 mg (200-mg tablet)
    Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (200-mg tablet)
  • Drug: Sorafenib 400 mg (Expansion)
    Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (200-mg tablet) expansion
  • Experimental: 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: Drug: Sorafenib 100 mg (50-mg tablet)
  • Experimental: 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: Drug: Sorafenib 200 mg (50-mg tablet)
  • Experimental: 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: Drug: Sorafenib 400 mg (50-mg tablet)
  • Experimental: 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: Drug: Sorafenib 400 mg (200-mg tablet)
  • Experimental: 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: Drug: Sorafenib 400 mg (Expansion)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
158
April 2008
May 2005   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00941863
100375
No
Not Provided
Not Provided
Bayer
Bayer
Onyx Pharmaceuticals
Study Director: Bayer Study Director Bayer
Bayer
February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP