Phase I Study of ZD4054 (Zibotentan) and Docetaxel in Patients With Metastatic HRPC

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00314782
First received: April 13, 2006
Last updated: March 11, 2013
Last verified: March 2010

April 13, 2006
March 11, 2013
March 2006
March 2008   (final data collection date for primary outcome measure)
Part A: Maximum Tolerated Dose (MTD) [ Time Frame: Part A: Cycle 1 ('Primary analysis' corresponding to data cut-off 5th March 2008) ] [ Designated as safety issue: Yes ]
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Complete list of historical versions of study NCT00314782 on ClinicalTrials.gov Archive Site
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Phase I Study of ZD4054 (Zibotentan) and Docetaxel in Patients With Metastatic HRPC
A Phase I Study of ZD4054 (Zibotentan) in Combination With Docetaxel in 2 Parts, an Open-Label, Non-Randomized, Dose-Finding Part and a Double-Blind, Placebo-Controlled, Randomized Dose Expansion Part, in Patients With Metastatic Hormone-Refractory Prostate Cancer

Two-part, multi-center study design to establish a maximum tolerated dose (MTD) of ZD4054 in combination with docetaxel and to explore its safety, tolerability, pharmacokinetic (PK) profiles and clinical efficacy in patients with metastatic hormone-refractory prostate cancer (HRPC)

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Prostate Cancer
  • Drug: ZD4054 (Zibotentan)
    oral tablet
    Other Name: Zibotentan
  • Drug: Docetaxel
    intravenous infusion
    Other Name: Taxotere®
  • Drug: Placebo
  • Experimental: Part A
    Part A (dose-finding): ZD4054 (Zibotentan) 10 mg oral tablet once daily, with docetaxel 75mg/m^2 intravenous infusion once per cycle
    Interventions:
    • Drug: ZD4054 (Zibotentan)
    • Drug: Docetaxel
  • Experimental: Part A (ZD4054 (Zibotentan) 15 mg + docetaxel)
    Part A (dose-finding): ZD4054 (Zibotentan) 15 mg oral tablet once daily, with docetaxel 75mg/m^2 intravenous infusion once per cycle
    Interventions:
    • Drug: ZD4054 (Zibotentan)
    • Drug: Docetaxel
  • Experimental: Part B
    Part B (randomised, placebo-controlled): ZD4054 (Zibotentan) Maximum Tolerated Dose (MTD), 15mg, oral tablet once daily, with docetaxel 75mg/m^2 intravenous infusion once per cycle
    Interventions:
    • Drug: ZD4054 (Zibotentan)
    • Drug: Docetaxel
  • Experimental: Part B (placebo)
    Part B (randomised, placebo-controlled): Matching placebo oral tablet once daily, with docetaxel 75mg/m^2 intravenous infusion once per cycle
    Interventions:
    • Drug: Docetaxel
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
44
March 2009
March 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Provision of informed consent
  • Histological or cytological confirmation of prostate cancer
  • Evidence of metastatic disease on CT scan, MRI, or bone scan
  • Surgically or continuously medically castrated with LHRH analogue
  • Progressive disease after most recent therapy

    • Disease progression by CT/MRI
    • Bone scan progression: appearance of 1 or more new lesions since last bone scan
    • Rising PSA
  • World health organization (WHO) performance status 0 to 2
  • Life expectancy of 12 weeks or longer

Exclusion Criteria:

  • Use of anti-hormonal therapies (including ketoconazole, aminoglutethimide, finasteride and anti-androgen therapies) within 4 weeks of starting study treatment, except for bicalutamide and nilutamide which are excluded within 6 weeks of starting study treatment. Estramustine or estrogens, if taken, have to be stopped at least 4 weeks before starting treatment.
  • Definite or suspected personal history or family history of adverse drug reactions, or hypersensitivity to drugs that are endothelin antagonist; history of severe hypersensitivity reactions to drugs formulated with polysorbate 80.
  • Prior cytotoxic chemotherapy for metastatic prostate cancer
  • Radiotherapy within 4 weeks before the start of study therapy
  • Systemic radionuclide therapy (ie strontium chloride Sr89, 186Re-labeled HEDP, or 153Sm-EDTMP pentasodium) within 12 weeks before entering study
  • Use of potent CYP450 inhibitors (such as itraconazole, ritonavir, indinavir, erythromycin, troleandomycin, clarithromycin, diltiazem, verapamil) within 2 weeks before study entry.
  • Use of potent CYP450 inducers (such as phenytoin, rifampicin, carbamazepine and phenobarbitone, St. John's Wort) within 2 weeks before study entry.

NOTE: Dexamethasone is a known inducer of CYP2D6 and CYP3A4 but is not considered exclusionary for purposes of this study.

  • New neurologic symptoms or signs consistent with acute or evolving spinal cord compression confirmed by magnetic resonance imaging (MRI) (except for those previously treated and have stable symptoms).
  • History of past or current epilepsy, epilepsy syndrome, or other seizure disorder
  • History of Migraine or chronic headache
  • Symptomatic central nervous system (CNS) metastases
  • Absolute Neutrophil Count (ANC) <1.5 x 109/L (1,5000/mm3)
  • Platelet count < 100 x 109/L (100,000/mm3)
  • Serum bilirubin greater than the upper limit of normal (ULN)
  • Alanine amino transferase (ALT) or aspartate amino transferase (AST) greater than 1.5 times the upper limit of normal (ULN)
  • Creatinine clearance <50 mL/min
  • QT interval corrected for heart rate by the Barrett Formula (QTc) > 470 msec at screening
  • New York Heart Association (NYHA) class II-IV Heart Disease
  • Myocardial infarction (heart attack) within past 3 months
  • CTCAE grade ≥2 Peripheral Neuropathy
  • Treatment with a non-approved or investigational drug within 30 days before study entry
  • Evidence of any other significant clinical symptoms, abnormal laboratory findings or recent surgery that patients has not recovered from that make it undesirable for the patient to participate in the study in the opinion of the investigator(s)
  • Involvement in the planning and conduct of the study
  • Previous treatment in the present study
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Germany,   United Kingdom
 
NCT00314782
D4320C00020, 4054IL/0020
Not Provided
AstraZeneca
AstraZeneca
Not Provided
Study Director: AstraZeneca Emerging Oncology Medical Science Director, MD AstraZeneca
AstraZeneca
March 2010

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