A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF SUNITINIB PLUS PREDNISONE VERSUS PREDNISONE IN PATIENTS WITH PROGRESSIVE METASTATIC CASTRATION-RESISTANT PROSTATE CANCER AFTER FAILURE OF A DOCETAXEL-BASED CHEMOTHERAPY REGIMEN

• Register: EUCTR
• Last refreshed on: 22 October 2012
• Main ID: EUCTR2008-002158-40-DE
• Date of registration: 28/07/2008
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017, USA
• Public title: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF SUNITINIB PLUS PREDNISONE VERSUS PREDNISONE IN PATIENTS WITH PROGRESSIVE METASTATIC CASTRATION-RESISTANT PROSTATE CANCER AFTER FAILURE OF A DOCETAXEL-BASED CHEMOTHERAPY REGIMEN
• Scientific title: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF SUNITINIB PLUS PREDNISONE VERSUS PREDNISONE IN PATIENTS WITH PROGRESSIVE METASTATIC CASTRATION-RESISTANT PROSTATE CANCER AFTER FAILURE OF A DOCETAXEL-BASED CHEMOTHERAPY REGIMEN
• Date of first enrolment: 09/12/2008
• Target sample size: 819
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-002158-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Belgium, Czech Republic, Denmark, Finland, France, Germany, Italy, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Histologically- or cytologically-confirmed adenocarcinoma of the prostate.
2. Metastatic castration-resistant prostate cancer (refractory to androgen ablation). Patients must have surgical or ongoing chemical castration, with baseline testosterone level =50 ng/dL.
3. Patients must have disease that has failed one prior docetaxel-based chemotherapy regimen for the treatment of metastatic disease, defined as progression of disease on or after treatment (docetaxel-resistant), or be considered
docetaxel-intolerant (discontinued treatment due to unacceptable toxicity, as judged by the treating physician or by the patient). In the event both disease progression and drug intolerance are observed during prior docetaxelbased treatment, disease progression will be considered the dominant entry criterion.
4. Patients must have documented evidence of progressive disease defined by either:
• PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum
of one week apart with the last result being at least 2.0 ng/mL,
• New or increasing non-bone disease (RECIST), or
• Positive bone scan with 2 or more new lesions (PCWG2).
5. ECOG performance status 0 or 1.
6. Resolution of all acute toxic effects of prior therapy (except for alopecia and neuropathy) or surgical procedure to grade =1 or to baseline prior to therapy.
7. Adequate organ function as defined by the following criteria:
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase[SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) =2.5 x upper limit of normal (ULN), =5 x ULN for patients with liver metastases
• Total serum bilirubin =1.5 x ULN
• Absolute neutrophil count (ANC) =1500/µL
• Platelets =100,000/µL
• Hemoglobin =9.0 g/dL
• Serum creatinine =2 x ULN
• QTc interval =470 msec
• Left ventricular ejection fraction (LVEF) =lower limit of institutional normal (LLN) as assessed by multigated acquisition (MUGA) scan or echocardiogram (ECHO)
8. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the completion of patient reported outcomes questionnaires and an analgesic use diary.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects presenting with any of the following will not be included in the study:
1. Prior treatment with sunitinib (in any clinical setting) and/or more than one prior chemotherapy regimen in the metastatic disease treatment setting.
2. Chemotherapy within 3 weeks of the date of the first dose.
3. Radioisotope therapy with Strontium-89 or Samarium within 12 weeks of the date of the first dose.
4. Radiation therapy (including palliative radiotherapy to metastatic lesion(s)) within 2 weeks or major surgery (e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery) within 4 weeks of the date of the first dose.
5. Current treatment on another therapeutic clinical trial.
6. Impending complication from bone metastases (fracture and/or cord compression).
Properly treated or stabilized fractures and/or cord compression is allowed.
7. Presence of ongoing urinary obstruction (e.g., urinary retention, hydronephrosis) requiring medical intervention. Properly treated urinary obstruction is allowed.
8. Grade =3 hemorrhage within 4 weeks of the date of the first dose.
9. Ongoing cardiac dysrhythmias of grade =2.
10. Hypertension that cannot be controlled by medications (>150 mmHg systolic or >100 mmHg diastolic despite optimal medical therapy).
11. Ongoing treatment with therapeutic doses (with therapeutic INR levels) of coumarinderivatives or oral antivitamin K agents.
12. Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, stage I carcinoma fully treated, or in situ carcinoma that have been adequately treated with no evidence of recurrent disease for 12 months.
13. Any of the following within the 6 months prior to study drug administration: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure,
pulmonary embolism, cerebrovascular accident, or transient ischemic attack.
14. History of, or known brain metastases (skull metastases allowed) and/or carcinomatous meningitis (leptomeningeal disease).
15. Known human immunodeficiency virus (HIV) infection.
16. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Progressive metastatic castration-resistant prostate cancer after failure of a Docetaxel-based chemotherapy regimen.
MedDRA version: 9.1 Level: LLT Classification code 10062904 Term: Hormone-refractory prostate cancer

Intervention(s)

Trade Name: Sutent
Product Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib
CAS Number: 341031-54-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Sutent
Product Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib
CAS Number: 341031-54-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Sutent
Product Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib
CAS Number: 341031-54-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 37.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Sutent
Product Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib
CAS Number: 341031-54-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Pharmaceutical Form: Tablet
INN or Proposed INN: Prednisone
CAS Number: 53-03-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Secondary Objective: •To demonstrate superiority in the progression-free survival (PFS) of patients with progressive mCRPC treated with SP versus PP after failure of a docetaxel-based chemotherapy regimen.
• To compare the objective response rate (ORR) and duration of response (DR) in patients with progressive mCRPC treated with SP versus PP after failure of a docetaxel-based chemotherapy regimen.
• To compare patient reported outcomes (PROs) of pain severity, health-related quality of life, prostate cancerspecific symptoms, and general health status in patients with progressive mCRPC treated with SP versus PP after failure of a docetaxel-based chemotherapy regimen.
• To evaluate the safety and tolerability of sunitinib in combination with prednisone.

Main Objective: To demonstrate superiority in the overall survival (OS) of patients with progressive mCRPC treated with sunitinib plus prednisone (SP) versus placebo plus prednisone (PP) after failure of a docetaxel-based chemotherapy regimen.

Primary end point(s): Overall survival (OS)

Secondary ID(s)

2008-002158-40-ES

A6181120