Efficacy and Safety of Zactima™ in Patients With Castration-refractory Metastatic Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00659438
First received: April 10, 2008
Last updated: June 14, 2012
Last verified: June 2012
  Purpose

This randomized, double-blind phase II trial is to assess the efficacy and safety of bicalutamide (Casodex® ) associated to ZD6474 (Zactima™ ) or to placebo in patients with castration-refractory metastatic prostate cancer without any clinical symptom related to disease progression. The study is blinded, and subjects will be randomised (1:1 ratio) to either ZD6474 300 mg or placebo. The blinded design ensures robust, unbiased data collection and assessment. Placebo control is necessary to ensure a robust assessment of PSA PFS, and is acceptable in this subject population where all subjects will also received bicalutamide 150 mg o.d. Subjects will continue study treatment until they reach objective biological disease progression or unacceptable toxicity or withdrawal of consent or until end of trial (which event occurs first). The end of study is fixed 12 months after the last randomised patient's first dose of study treatment.


Condition Intervention Phase
Prostate Cancer
Drug: ZD6474 (Vandetanib)
Drug: Bicalutamide
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind Phase II Trial to Assess the Efficacy and Safety of Bicalutamide (Casodex® ) Associated to ZD6474 (Zactima™ ) or to Placebo in Patients With Castration-refractory Metastatic Prostate Cancer Without Any Clinical Symptom Related to Disease Progression

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Prostate Specific Antigen (PSA) Progression Free Rate at 4 Months [ Time Frame: 4 months ] [ Designated as safety issue: No ]

    To assess the effect of vandetanib on biological progression free rate based on PSA level (assessable set).

    PSA progression free rate defined as the number of participants with :

    • After decline from baseline: a 25% increase above the nadir
    • No decline from baseline: a 25% increase above the baseline (min. increase of 2 ng/mL)


Secondary Outcome Measures:
  • Progression Free Survival (PFS) at 4 Months (Instead of Time to PSA Progression) [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Due to the difficulties to assess biological progression date when clinical progression has occurred first, and because of the non-assessment of the clinical progression after treatment discontinuation, Time to PSA progression was not evaluated. PFS was evaluated instead, whether biological or clinical progression.

  • Progression Free Survival (PFS) at 4 Months (Instead of Time to Onset of Cancer-related Symptoms) [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Due to the difficulties to assess biological progression date when clinical progression has occurred first, and because of the non-assessment of the clinical progression after treatment discontinuation, Time to onset of cancer-related symptoms was not evaluated. PFS was evaluated instead, whether biological or clinical progression.

  • PSA Response Rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]

    To investigate the effect of vandetanib on the PSA response rate. PSA response rate defined by the number of participants with a PSA decrease relative to baseline of at least 50%.

    A minimum decrease of 2 ng/mL in absolute value and a confirmation on at least 2 consecutive occasions (at least 4 weeks apart) were requested.


  • Overall Survival (OS) [ Time Frame: End of study (July 2011) ] [ Designated as safety issue: No ]
    To investigate the effect of vandetanib on overall survival. Patients alive at the time of the statistical analysis were censored at the time they were last known to be alive. Due to censored data, median overall survival in the placebo group cannot be calculated. OS defined as the number of participants who were alive.

  • Progression Rate From the Radionuclide Bone Scanning [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    To describe the effect of vandetanib on progression rate from the radionuclide bone scanning in a sub-group of patients who had a bone scan within 3 to 6 months after 1st treatment dose. Number of participants with at least 2 new lesions on the radionuclide bone scan compared to baseline assessment were counted for calculation of progression rate.

  • Number of Circulating Tumour Cells (CTC) (in Patients Included in Ile de France Centres Only) [ Time Frame: 4 months ] [ Designated as safety issue: No ]

    To investigate the effect of vandetanib on CTC. Numbering of CTCs to be performed at baseline, 1 week, 1 and 2 months after randomisation. This study was proposed only to patients followed in a study centre located in Ile de France.

    Correlation between the number of CTCs and PSA response was to be estimated after 1 week, 1 and 2 months of treatment


  • Number of Circulating Endothelial Cells (CEC) of Tumour Blood Cells (in Patients Included in Ile de France Centres Only) [ Time Frame: 4 months ] [ Designated as safety issue: No ]

    To investigate the effect of vandetanib on CEC. Numbering of CECs was to be performed at baseline, 1 week, 1 month and 2 months after randomisation.

    Correlation between the number of CECs and PSA response was to be estimated after 1 week, 1 month and 2 months of treatment.


  • Number of Patients With CECs, CTCs and Gene Signature Profile of CTCs [ Time Frame: 4 months ] [ Designated as safety issue: No ]

    To investigate the relationship between response to vandetanib, CTCs and CECs. To investigate gene signature profile of antiangiogenic response by gene micro-array analysis of CTCs.

    Gene signature profile of CTCs was aimed to be compared before and after 2 months of treatment. No blood sample has been taken for the study, and so results on CTCs, CECs of tumour vessels and gene and signature profiles of CTCs were not performed.



Enrollment: 110
Study Start Date: February 2008
Study Completion Date: July 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Bicalutamide 150mg + ZD6474 300mg
Drug: ZD6474 (Vandetanib)
300mg orally, once daily
Other Name: Zactima
Drug: Bicalutamide
150mg orally, once daily
Other Name: Casodex
Placebo Comparator: 2
Bicalutamide 150mg + placebo
Drug: Bicalutamide
150mg orally, once daily
Other Name: Casodex
Drug: Placebo
orally, once daily

  Eligibility

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

Inclusion Criteria:

  • Males presented with a confirmed histological diagnosis of adenocarcinoma of the prostate with evidence of metastases (including bone, lymph nodes, or other site) radiologically or histologically documented and despite a serum testosterone ≤1.73 nmol/L (50 ng/dL) proving castration, evidence of biochemical progression of prostate cancer, documented by a rise in PSA .

Exclusion Criteria:

  • Radiotherapy or surgery or antiandrogens (except LHRH analogue) or bilateral orchiectomy within the 30 days preceding Visit 1. Incompletely healed surgical incision.
  • Concomitant anticancer therapy other than surgical castration or continuous medical castration.
  • Biology restriction.
  • Clinical significant cardiovascular event or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia.
  • History of arrhythmia which is symptomatic or requires treatment (CTCAE grade 3), symptomatic despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled on medication are permitted.
  • Hypertension not controlled by medical therapy
  • ECG /QTc prolongation
  • Presence of left bundle branch block (LBBB).
  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: NCT00659438

Locations
France
Research Site
Bordeaux Cedex, France
Research Site
Creteil, France
Research Site
Paris, France
Research Site
Reims Cedex, France
Research Site
Villejuif, France
Sponsors and Collaborators
AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00659438     History of Changes
Other Study ID Numbers: D4200C00080
Study First Received: April 10, 2008
Results First Received: November 14, 2011
Last Updated: June 14, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Bicalutamide
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014