Clinical trial NCT00314782: Phase I Study of ZD4054 (Zibotentan) and Docetaxel in Patients With Metastatic HRPC
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Cancer
Keywords: metastatic hormone-refractory prostate cancer (HRPC)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2006-04-17
Enrollment: 44
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


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

Primary outcomes:
measure: Part A: Maximum Tolerated Dose (MTD)
timeFrame: Part A: Cycle 1 ('Primary analysis' corresponding to data cut-off 5th March 2008)
Secondary outcomes:
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Research Site
state: New York
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Berlin
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Rostock
country: Germany
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Plymouth
country: United Kingdom
facility: Research Site
city: Surrey
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: AstraZeneca Emerging Oncology Medical Science Director, MD
role: STUDY_DIRECTOR
References: