A Phase IIa. Open-label, Multicenter, Dose-escalation Study to Assess the Tolerability and Pharmacokinetics of ZD4054 (Zibotentan) Given Orally Once Daily in Subjects With Metastatic Prostate Cancer

The primary purpose of this study is to determine the safest dose of ZD4054 (Zibotentan)in men with prostate cancer

Study Overview

• Status: Completed
• Conditions: Prostatic Neoplasms; Metastases, Neoplasm
• Intervention / Treatment: Drug: ZD4054 10 mg; Drug: ZD4054 15 mg; Drug: ZD4054 22.5 mg

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Research Site
  • Wisconsin
    • Madison, Wisconsin, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Men 18 years & older
• Confirmed diagnosis of prostate cancer with bone metastases

Exclusion Criteria:

• No more than 2 prior chemotherapy regimens
• No radiation, chemotherapy or bisphosphonates in the past 4 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZD4054 10 mg; 1 x 10 mg oral tablets once daily	Drug: ZD4054 10 mg; 1 x 10 mg oral tablets once daily; Other Names: Zibotentan,
Experimental: ZD4054 15 mg; 1 x 10 mg + 2 x 2.5 mg oral tablets once daily	Drug: ZD4054 15 mg; 1 x 10 mg + 2 x 2.5 mg oral tablets once daily; Other Names: Zibotentan
Experimental: ZD4054 22.5 mg; 2 x 10 mg + 1 x 2.5 mg oral tablets once daily	Drug: ZD4054 22.5 mg; 2 x 10 mg + 2 x 2.5 mg oral tablets once daily; Other Names: Zibotentan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicities (DLTs)	DLT is defined as experiencing Common Toxicity Criteria (CTC) grade 3 or 4 headache with onset within 24 h of receiving ZD4054, CTC grade 2 rhinitis leading to the withdrawal of the subject, or other CTC grade 3 or 4 toxicity that was considered to be related to ZD4054 treatment. The numbers of patients with a DLT are reported.	Baseline to Day 29.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Prostate Specific Antigen (PSA) Concentration	Total Prostate Specific Antigen (PSA) concentration at Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2).	Baseline to Day 15.
Change in Total Prostate Specific Antigen (PSA)	Percentage change in total Prostate Specific Antigen (PSA) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100	Baseline to Day 15.
Change in Serum Concentration of Bone Alkaline Phosphatase (ALP)	Percentage change in serum concentration of Bone Alkaline Phosphatase (ALP) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100	Baseline to Day 15.
Change in Serum Concentration of Procollagen Type I N Propeptide (PINP)	Percentage change in serum concentration of Procollagen Type I N Propeptide (PINP) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100	Baseline to Day 15.
Change in Serum Concentration of C-Terminal Telopeptide of Type I Collagen (CTx)	Percentage change in serum concentration of C-Terminal Telopeptide of Type I Collagen (CTx) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100	Baseline to Day 15.
Change in Urine Concentration of Type I Collagen-Cross Linked N Telopeptide (NTx)	Percentage change in urine concentration of Type I Collagen-Cross Linked N Telopeptide (NTx) (nmol BCE/mmol Creatinine) from baseline to Day 15 (14 doses of study treatment per patient - no dose was administered on Day 2). Percentage change = [(measure at Day 15 - measure at baseline)/measure at baseline]*100	Baseline to Day 15.

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): October 1, 2005
• Study Completion (Actual): October 1, 2005

Study Registration Dates

• First Submitted: March 3, 2003
• First Submitted That Met QC Criteria: March 3, 2003
• First Posted (Estimate): March 4, 2003

Study Record Updates

• Last Update Posted (Estimate): October 31, 2012
• Last Update Submitted That Met QC Criteria: October 23, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: prostate cancer; Metastatic prostate cancer; bone metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplastic Processes; Neoplasms; Prostatic Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: 4054IL/0004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No