A Safety Study of ZD4054 in Prior Chemotherapy Treated Patients With Metastatic Hormone-resistant Prostate Cancer (DAPROCA-1)

This study has been terminated.
(A consequence of the results of the ENTHUSE phase III study program)
Sponsor:
Collaborator:
Rigshospitalet, Denmark
Information provided by (Responsible Party):
Michael Borre, Aarhus University Hospital
ClinicalTrials.gov Identifier:
NCT01000948
First received: October 22, 2009
Last updated: January 7, 2014
Last verified: July 2011
  Purpose

This is a prospective, open, one-arm, two-centre, Phase II clinical safety pilot-study. The trial is designed to gain initial safety and efficacy-related data on once-daily orally administered ZD4054 10 mg in prior chemotherapy treated patients with metastatic hormone-resistant prostate cancer.


Condition Intervention Phase
Prostate Cancer
Metastasis
Drug: ZD4054
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Phase II, Two-centre, 1-Arm Safety Study of Once-daily Orally Administered 10 mg ZD4054 in Prior Chemotherapy Treated Patients With Metastatic Hormone-resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Aarhus University Hospital:

Primary Outcome Measures:
  • To assess the safety and tolerability profile of ZD4054 after treatment with chemotherapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Vital signs [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Laboratory data [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • ECGs [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Physical Exam [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Death from any cause [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To investigate the effect of ZD4054 on rate of rise of PSA [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To investigate the effect of ZD4054 on prostate cancer related pain [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To investigate the effect of ZD4054 on the plasma concentration of circulating tumour cells (CTC). [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: October 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ZD4054
The study had only one arm: intervention
Drug: ZD4054
ZD4054 10 mg given orally, once daily in tablet form to all patients in two years or until investigator consider the drug for useless.

  Hide Detailed Description

Detailed Description:

Study centres and number of patients planned This pilot study will be conducted in approximately 24 patients recruited from two hospital-based Danish centres: department of Urology K, Aarhus University Hospital, Skejby and department of Urologic Surgery D, Rigshospitalet. The recruitment of patients will be competitive among centres. 1-2 months before expected LSI it should be discussed if the target accrual should be expanded.

Study period Phase of development Estimated date of first patient enrolled August 1th 2009 II Estimated date of last patient completed July 31th 2012 Total study duration is approximately 36 months, which includes 12 months' recruitment, 36-month follow-up for safety and final survival analysis.

Objectives

The primary objective of this study is:

To assess the safety and tolerability profile of ZD4054 after treatment with chemotherapy

  • Adverse events
  • Vital signs
  • Laboratory data
  • ECGs
  • Physical Exam
  • Death from any cause

The secondary objectives of the study are:

  1. To investigate the effect of ZD4054 on rate of rise of PSA
  2. To investigate the effect of ZD4054 on prostate cancer related pain
  3. To investigate the effect of ZD4054 on the plasma concentration of circulating tumour cells (CTC).

In addition, Time to Progression and Overall Survival (time to death) will be compared with historical data in a post chemotherapy population.

Study design This is a prospective, Open, One-arm, Phase II clinical safety pilot-study. The trial is designed to gain initial safety and efficacy-related data on once-daily orally administered ZD4054 10 mg in prior chemotherapy treated patients with metastatic hormone-resistant prostate cancer.

Patients could receive other therapies including prednisolone, estramustine, ketoconazole and second-line or third-line antiandrogens at investigator's discretion without being considered treatment failures or having to stop study therapy; however every attempt will be made to avoid changes in medication for at least 12 weeks to minimise potential for confounding on study endpoints over this time period. Chemotherapy and radiation therapy may also be administered in addition to study therapy at investigator's discretion after objective progression if the patient is considered likely to derive benefit. Patients will be followed to death.

Target patient population A total number of 24 male patients aged 18 years or older with metastatic hormone-resistant prostate cancer who have progressive disease (defined by rising serum prostate-specific antigen levels despite medical or surgical castration) and previously received cytotoxic chemotherapy (docetaxel) for the treatment of HRPC.

Investigational product, dosage and mode of administration

Patients will not be randomised and all patients will receive:

• ZD4054 10 mg given orally, once daily in tablet form. Duration of treatment Patients will receive daily ZD4054 as long as they meet no withdrawal criteria. Following completion of 24 months of ZD4054, patients, who in the investigator's opinion are experiencing benefit from study treatment, may continue on ZD4054, for as long as they meet no withdrawal criteria.

Statistical methods The study is a pilot study designed to collect safety/tolerability data and assess markers of efficacy. A total of 24 patients will be recruited into this pilot study and this is based primarily on the number of patients that can be recruited in a reasonable time period at the centres and should be sufficient to make an initial assessment of safety/tolerability and the efficacy markers.

For the assessment of tolerability and safety, incidence and severity of adverse events (AEs) (based on National Cancer Institute Common Terminology Criteria for Adverse Events, version 3 (NCI CTCAE) grading), laboratory values, vital signs, ECGs and physical exam will be summarised.

Secondary endpoints will be presented and analysed to investigate trends in the data. The interpretation of the analyses will consider the number of assessments being undertaken.

Pain will be assessed using the Brief Pain Inventory Demography and baseline data will be summarised. Any analyses will be performed using SPSS and other validated software as appropriate.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of informed consent
  2. Male, aged 18 years or older
  3. Histological or cytological confirmation of adenocarcinoma of the prostate
  4. Documented evidence of bone metastasis on bone scans.
  5. Surgically castrated or continuously medically castrated with serum testosterone less than 2.4 nmol/L (70 ng/dL).
  6. Previously (not inside 8 weeks) treated with at least two times 75 mg/m2 docetaxel.
  7. Biochemical progression of prostate cancer after chemotherapy, documented while the patient is castrate:

    o Biochemical progression is defined as at least 2 stepwise increases (≥1ng/mL) in PSA over a period of ≥1 month (values do not need to be consecutive but 2 values that have increased since the previous highest value are required) with at least 14 days between each measurement irrespective of assay or laboratory.

  8. Life expectancy of 3 months or more.

Exclusion Criteria:

  1. Use of potent CYP450 inducers (such as phenytoin, rifampicin, carbamazepine, phenobarbitone and St John's Wort) within 2 weeks of starting study treatment. Dexamethasone will be allowed if the investigator feels it is necessary but is encouraged to use a different form of steroid treatment wherever possible
  2. Have received investigational drug in another clinical study of anticancer therapy, within 4 weeks of starting study treatment
  3. Hypersensitivity to endothelin antagonists
  4. Neurological symptoms or signs consistent with acute or evolving spinal cord compression. If a patient has neurologic symptoms, an MRI must be performed that demonstrates no impending or actual spinal cord compression. Stable, previously treated patients are allowed
  5. History of past or current epilepsy, epilepsy syndrome, or other seizure disorder
  6. Stage II, III or IV cardiac failure (classified according to New York Heart Association (NYHA) classification) or myocardial infarction within 6 months prior to study entry
  7. QT interval corrected for heart rate e.g., by Bazett's correction >470 msec
  8. In the opinion of the investigator, any evidence of severe or uncontrolled systemic disease (e.g., currently unstable or uncompensated respiratory, cardiac, hepatic or renal disease) or evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
  9. Hemoglobin (Hb) <5 mmol/L. Concomitant use of erythropoietin or blood transfusions is allowed
  10. Serum bilirubin >1.5 times the upper limit of normal (ULN). This will not apply to patients with Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology), who will be allowed in consultation with their physician
  11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times the ULN or 5 times the ULN in the presence of liver metastasis
  12. Creatinine clearance of <50 mL/minute, determined using the Cockcroft-Gault equation or by 24-hour creatinine clearance
  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: NCT01000948

Locations
Denmark
Dpt of Urology,Aarhus University Hospital
Aarhus, Denmark, 8200
Sponsors and Collaborators
Aarhus University Hospital
Rigshospitalet, Denmark
Investigators
Study Chair: Michael Borre, MD Phd DMSc Dpt Urology Aarhus University Hospital - DAPROCA
  More Information

No publications provided

Responsible Party: Michael Borre, Professor, DMSci, PhD, Aarhus University Hospital
ClinicalTrials.gov Identifier: NCT01000948     History of Changes
Other Study ID Numbers: ISSIS40540005, DAPROCA-1
Study First Received: October 22, 2009
Last Updated: January 7, 2014
Health Authority: United States: Food and Drug Administration
Denmark: Danish Medicines Agency
Denmark: The Danish National Committee on Biomedical Research Ethics
Denmark: Good Clinical Practise

Keywords provided by Aarhus University Hospital:
Prostate cancer
Castration resistant
Chemotherapy resistant
Endothelial receptor A inhibitor
ZD4054

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 21, 2014