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
  Purpose

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.


Condition Intervention Phase
Carcinoma
Drug: Sorafenib 100 mg (50-mg tablet)
Drug: Sorafenib 200 mg (50-mg tablet)
Drug: Sorafenib 400 mg (50-mg tablet)
Drug: Sorafenib 400 mg (200-mg tablet)
Drug: Sorafenib 400 mg (Expansion)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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.


Enrollment: 158
Study Start Date: July 2002
Study Completion Date: April 2008
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
Drug: Sorafenib 100 mg (50-mg tablet)
Sorafenib (Nexavar, BAY43-9006) 100 mg twice daily (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).
Drug: Sorafenib 200 mg (50-mg tablet)
Sorafenib (Nexavar, BAY43-9006) 200 mg twice daily (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).
Drug: Sorafenib 400 mg (50-mg tablet)
Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (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).
Drug: Sorafenib 400 mg (200-mg tablet)
Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (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.
Drug: Sorafenib 400 mg (Expansion)
Sorafenib (Nexavar, BAY43-9006) 400 mg twice daily (200-mg tablet) expansion

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00941863

Locations
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Nashville, Tennessee, United States, 37232
United States, Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Bayer
Onyx Pharmaceuticals
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00941863     History of Changes
Other Study ID Numbers: 100375 
Study First Received: June 12, 2009
Results First Received: February 3, 2010
Last Updated: February 24, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Sorafenib
Advanced Solid Tumors
Maximum tolerated dose
Carboplatin and paclitaxel chemotherapy combination

Additional relevant MeSH terms:
Paclitaxel
Sorafenib
Albumin-Bound Paclitaxel
Carboplatin
Niacinamide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 25, 2016