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

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT00314782
Collaborator
(none)
44
Enrollment
9
Locations
4
Arms
36
Duration (Months)
4.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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)

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
44 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Mar 1, 2006
Actual Primary Completion Date :
Mar 1, 2008
Actual Study Completion Date :
Mar 1, 2009

Arms and Interventions

Arm Intervention/Treatment
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

Drug: ZD4054 (Zibotentan)
oral tablet
Other Names:
  • Zibotentan

    • Drug: Docetaxel
    intravenous infusion
    Other Names:
  • Taxotere®

    		•
    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

    Drug: ZD4054 (Zibotentan)
    oral tablet
    Other Names:
  • Zibotentan

    • Drug: Docetaxel
    intravenous infusion
    Other Names:
  • Taxotere®

    		•
    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

    Drug: ZD4054 (Zibotentan)
    oral tablet
    Other Names:
  • Zibotentan

    • Drug: Docetaxel
    intravenous infusion
    Other Names:
  • Taxotere®

    		•
    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

    Drug: Docetaxel
    intravenous infusion
    Other Names:
  • Taxotere®

    • Drug: Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Part A: Maximum Tolerated Dose (MTD) [Part A: Cycle 1 ('Primary analysis' corresponding to data cut-off 5th March 2008)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Buffalo New York United States
    2 Research Site Greenville South Carolina United States
    3 Research Site Nashville Tennessee United States
    4 Research Site Berlin Germany
    5 Research Site Dresden Germany
    6 Research Site Rostock Germany
    7 Research Site London United Kingdom
    8 Research Site Plymouth United Kingdom
    9 Research Site Surrey United Kingdom

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Study Director: AstraZeneca Emerging Oncology Medical Science Director, MD, AstraZeneca

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT00314782
    Other Study ID Numbers:
    • D4320C00020
    • 4054IL/0020
    First Posted:
    Apr 17, 2006
    Last Update Posted:
    Mar 12, 2013
    Last Verified:
    Mar 1, 2010
    Keywords provided by AstraZeneca
    metastatic hormone-refractory prostate cancer (HRPC)
    Additional relevant MeSH terms:
    Prostatic Neoplasms
    Docetaxel

    Study Results

    No Results Posted as of Mar 12, 2013