A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) and Docetaxel in Metastatic Hormone Resistant Prostate Cancer

Browse trials for

• Prostatic Neoplasms 6,370

Keywords

• Hormone Resistant Prostate Cancer
• Endothelin A Receptor Antagonist
• Endothelin A
• Endothelin A antagonist

Prostatic Neoplasms

6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.

This study's enrollment of 1,494 is above the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.

Lead sponsor

AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.

Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.

Study arms

• Active comparator
  Placebo + Docetaxel

  placebo oral tablet once daily + docetaxel intravenous infusion every 3 weeks

  Drug: Docetaxel · Drug: Placebo

• Experimental
  ZD4054 + Docetaxel

  ZD4054 10 mg oral tablet once daily + docetaxel intravenous infusion every 3 weeks

  Drug: Docetaxel · Drug: ZD4054

Interventions

• DrugDocetaxel

  intravenous infusion given every three weeks

  Also known as: Taxotere®

• DrugZD4054

  10 mg oral once daily dose

  Also known as: Zibotentan

• DrugPlacebo

  placebo oral tablet once daily

Primary outcomes

1. Overall Survival

   Median time (in months) from randomisation until death using the Kaplan-Meier method.

   Time frame: Patients were followed for survival up to 40 months

Secondary outcomes

1. Progression Free Survival

   Median time (in months) from randomisation until clinical progression of disease using the Kaplan-Meier method. Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline

   Time frame: Patients were followed for progression up to 40 months

2. Incidence of Skeletal Related Events

   Median time (in months) from randomisation until occurrence of a skeletal related event using the Kaplan-Meier method, where skeletal related event is defined as the first occurrence of a pathological fracture, a vertebral compression fracture not related to trauma, prophylactic surgery or radiation for impending fracture or spinal cord compression, or a spinal cord compression.

   Time frame: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)

3. Time to Prostate-specific Antigen (PSA) Progression

   Median time (in months) from randomisation until first PSA value \>50% higher than baseline of at least 5ng/ml seen in at least 2 consecutive PSA values at least 2 weeks apart using the Kaplan-Meier method.

   Time frame: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)

4. Time to Pain Progression

   Median time (in months) from randomisation until date of first assessment of increased pain using the Kaplan-Meier method, where increased pain event is defined as the first of a patient requiring opiate medication for duration of ≥1 week for pain due to prostate cancer metastasis, pain due to metastasis that has an increase in the worst pain item of the Brief Pain Inventory (BPI) from baseline to a minimum score of 5 with no decrease in analgesic use, or pain due to metastasis requiring radionuclide therapy, radiation therapy or surgery.

   Time frame: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)

5. Pain Response

   Number of patients with a pain response, defined as a decrease in brief pain inventory questionnaire (BPI) of at least 2 points from baseline or a decrease in opiate use of 25% from baseline.

   Time frame: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)

6. Health Related Quality of Life

   Median time (in months) from randomisation until deterioration of Health Related Quality of Life using the Kaplan-Meier method, where deterioration is defined as a change from baseline of less than or equal to -6 points in Total FACT-P score maintained for 2 consecutive visits.

   Time frame: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)

7. PSA Response

   PSA response defined as \>50% decrease in serum PSA values from baseline seen in at least 2 consecutive PSA values at least 2 weeks apart.

   Time frame: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)

Baseline characteristics

Publications

• Fizazi K, Higano CS, Nelson JB, Gleave M, Miller K, Morris T, Nathan FE, McIntosh S, Pemberton K, Moul JW. Phase III, randomized, placebo-controlled study of docetaxel in combination with zibotentan in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2013 May 10;31(14):1740-7. doi: 10.1200/JCO.2012.46.4149. Epub 2013 Apr 8. Erratum In: J Clin Oncol. 2014 Oct 20;32(30):3461. Fizazi, Karim S [Corrected to Fizazi, Karim]. PubMed 23569308 ↗