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
  Purpose

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 Intervention Phase
Prostate Cancer
Drug: ZD4054 (Zibotentan)
Drug: Docetaxel
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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 ]

Enrollment: 44
Study Start Date: March 2006
Study Completion Date: March 2009
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Zibotentan
Drug: Docetaxel
intravenous infusion
Other Name: 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 Name: Zibotentan
Drug: Docetaxel
intravenous infusion
Other Name: 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 Name: Zibotentan
Drug: Docetaxel
intravenous infusion
Other Name: 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 Name: Taxotere®
Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
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: NCT00314782

Locations
United States, New York
Research Site
Buffalo, New York, United States
United States, South Carolina
Research Site
Greenville, South Carolina, United States
United States, Tennessee
Research Site
Nashville, Tennessee, United States
Germany
Research Site
Berlin, Germany
Research Site
Dresden, Germany
Research Site
Rostock, Germany
United Kingdom
Research Site
London, United Kingdom
Research Site
Plymouth, United Kingdom
Research Site
Surrey, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: AstraZeneca Emerging Oncology Medical Science Director, MD AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00314782     History of Changes
Other Study ID Numbers: D4320C00020, 4054IL/0020
Study First Received: April 13, 2006
Last Updated: March 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
metastatic hormone-refractory prostate cancer (HRPC)

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014