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

NCT ID: NCT00314782

Last Updated: 2013-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2009-03-31

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)

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part A

Part A (dose-finding): ZD4054 (Zibotentan) 10 mg oral tablet once daily, with docetaxel 75mg/m\^2 intravenous infusion once per cycle

Group Type: EXPERIMENTAL

ZD4054 (Zibotentan)

Intervention Type: DRUG

oral tablet

Docetaxel

Intervention Type: DRUG

intravenous infusion

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

Group Type: EXPERIMENTAL

ZD4054 (Zibotentan)

Intervention Type: DRUG

oral tablet

Docetaxel

Intervention Type: DRUG

intravenous infusion

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

Group Type: EXPERIMENTAL

ZD4054 (Zibotentan)

Intervention Type: DRUG

oral tablet

Docetaxel

Intervention Type: DRUG

intravenous infusion

Part B (placebo)

Part B (randomised, placebo-controlled): Matching placebo oral tablet once daily, with docetaxel 75mg/m\^2 intravenous infusion once per cycle

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

intravenous infusion

Placebo

Intervention Type: DRUG

Interventions

ZD4054 (Zibotentan)

oral tablet

Intervention Type: DRUG

Docetaxel

intravenous infusion

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Zibotentan; Taxotere®

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AstraZeneca Emerging Oncology Medical Science Director, MD

Role: STUDY_DIRECTOR

AstraZeneca

Locations

Research Site

Buffalo, New York, United States

Research Site

Greenville, South Carolina, United States

Research Site

Nashville, Tennessee, United States

Research Site

Berlin, , Germany

Research Site

Dresden, , Germany

Research Site

Rostock, , Germany

Research Site

London, , United Kingdom

Research Site

Plymouth, , United Kingdom

Research Site

Surrey, , United Kingdom

Countries

United States; Germany; United Kingdom

Other Identifiers

4054IL/0020

Identifier Type: -

Identifier Source: secondary_id

D4320C00020

Identifier Type: -

Identifier Source: org_study_id