The Pharmacokinetics and Safety Characteristics of Docetaxel in Patients With Cancer

A Phase 1, Double-blinded, Randomised, Multi-centre, Three-period, Three-treatment, Crossover Study to Compare the Intravenous Pharmacokinetic and Safety Characteristics of European Taxotere® and American Taxotere® With Hospira Docetaxel Injection Administered at a Therapeutic Dose in Cancer Patients.

The purpose of this study is to compare the pharmacokinetic and safety characteristics of European Taxotere® and American Taxotere® with Hospira Docetaxel injection in patients with cancer.

No information is available on the pharmacokinetic characteristics, safety or efficacy of Hospira Docetaxel Injection. The primary purpose of this study therefore is to compare the pharmacokinetic characteristics of 60-100 mg/m² Hospira Docetaxel Injection, 60-100 mg/m² European Taxotere® (Taxotere® EU) and 60-100 mg/m² American Taxotere® (Taxotere® US) when administered as a 1 hour intravenous infusion in man. The secondary objective of this study will be to compare the safety and tolerability of Hospira Docetaxel Injection, Taxotere® EU and Taxotere® US. The study will also provide an opportunity to assess selected efficacy endpoints according to local practice after each cycle of treatment.

The study dosing regimen (60-100 mg/m², administered as a 1 hour intravenous infusion at 3 week intervals) and subject population (cancer patients for whom Taxotere® monotherapy would be a suitable treatment option) were selected on the basis of the licensed use of 60-100 mg/m² Taxotere®. The randomised crossover design was chosen to reduce the effect of intersubject variation.

Since Hospira Docetaxel Injection has not been administered to man there is no information on the risks associated with its clinical use. However the active ingredient of Hospira Docetaxel Injection is the same as that of Taxotere® and it is expected that Hospira Docetaxel Injection will exhibit a similar safety and tolerability profile.

An estimated 24 patients will be recruited at several United Kingdom sites and one Russian site to provide 19 evaluable patients

Inclusion Criteria:

• Written informed consent given;

• Have medically documented cancer for which Taxotere® monotherapy would be a suitable treatment option;

• Aged ≥18 years;

• Eastern Cooperative Oncology Group (ECOG) performance status between 0 - 1 (inclusive);

• Haematological and serum chemical parameters that comply with the following criteria (based on local laboratory normal reference range):

  • Haemoglobin ≥9.5 g/dL
  • Leukocytes ≥3.0 x 10^9/L
  • Neutrophils ≥1.5 x 10^9/L
  • Platelets ≥100 x 10^9 L
  • Total bilirubin ≤2.0 x Upper Limit of Normal (ULN)
  • Aspartate aminotransferase (AST) ≤2.5 x ULN
  • Alanine aminotransferase (ALT) ≤2.5 x ULN
  • Alkaline phosphatase ≤4.0 x ULN
  • Serum creatinine ≤1.5 x ULN

• Willing to use an effective method of contraception, i.e. intrauterine device (IUD), oral contraceptive, subdermal implant or double barrier (condom with a contraceptive sponge or contraceptive suppository), unless anatomically sterile, from screening until at least 12 weeks after last dose of Investigational Medicinal Product.

• Willing and able to comply with the requirements of the protocol and available for the planned duration of the study.

Exclusion Criteria:

• Concomitant treatment with any other cytotoxic agent;
• Concomitant use of compounds that induce, inhibit or are metabolized by cytochrome P450, e.g. ciclosporin, ketoconazole, erythromycin, St John's Wort;
• History or presence of any clinically significant findings that, in the opinion of the Investigator, would preclude inclusion in the study;
• Clinically significant vital signs or 12-lead electrocardiogram (ECG) results, as judged by the Investigator;
• Participation in any other clinical trial using an Investigational Medicinal Product within the previous month
• History of Hepatitis B Virus, Hepatitis C Virus or Human Immunodeficiency Virus;
• Recent or clinically significant history of drug or alcohol abuse;
• Insulin-dependent or unstable Diabetes Mellitus;
• History of severe hypersensitivity reactions to Taxotere® or to other drugs formulated with Polysorbate 80;
• History of reaction to any drug containing polyethylene glycol 300 (PEG 300);
• Pregnancy or lactation.