A PHASE 2, RANDOMIZED, NON-COMPARATIVE, TWO-ARM OPEN LABEL, MULTIPLE-CENTER STUDY OF CP-751,871 IN COMBINATION WITH DOCETAXEL/PREDNISONE IN CHEMOTHERAPY- NAÏVE (ARM A) AND DOCETAXEL/PREDNISONE REFRACTORY (ARM B) PATIENTS WITH HORMONE INSENSITIVE PROSTATE CANCER

• Register: EUCTR
• Last refreshed on: 18 April 2012
• Main ID: EUCTR2005-002717-21-NL
• Date of registration: 30/08/2007
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. 235 East 42nd Street, New York, NY 10017
• Public title: A PHASE 2, RANDOMIZED, NON-COMPARATIVE, TWO-ARM OPEN LABEL, MULTIPLE-CENTER STUDY OF CP-751,871 IN COMBINATION WITH DOCETAXEL/PREDNISONE IN CHEMOTHERAPY- NAÏVE (ARM A) AND DOCETAXEL/PREDNISONE REFRACTORY (ARM B) PATIENTS WITH HORMONE INSENSITIVE PROSTATE CANCER
• Scientific title: A PHASE 2, RANDOMIZED, NON-COMPARATIVE, TWO-ARM OPEN LABEL, MULTIPLE-CENTER STUDY OF CP-751,871 IN COMBINATION WITH DOCETAXEL/PREDNISONE IN CHEMOTHERAPY- NAÏVE (ARM A) AND DOCETAXEL/PREDNISONE REFRACTORY (ARM B) PATIENTS WITH HORMONE INSENSITIVE PROSTATE CANCER
• Date of first enrolment: 17/01/2008
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002717-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: Double blind: Parallel group: yes Cross over: Other: If controlled, specify comparator, Other Medicinial Product: yes Placebo: Other:

Countries of recruitment

Germany, Netherlands, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically confirmed adenocarcinoma of the prostate (a new diagnostic biopsy is not required).
2. At least 18 years old.
3. PSA above 20 ng/mL.
4. Evidence of metastatic disease either on bone or CT scans.
5. Progressive disease after at least 1 hormonal treatment (orchiectomy, estrogens, LHRH therapy etc.) with documented testosterone levels less than 50 ng/dL and progressive disease defined by the following:
• An increase in PSA>50% over nadir value on hormonal therapy measured on 3 successive occasion at least 1 week a part. If the third measurement is lower than the second a fourth measurement will be taken. Only if the fourth measurement is higher than the second, the patient will be enrolled in the study.
6. Concurrent use of LHRH agonist is required if the patient has not been surgically castrated.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 determined within 2 weeks prior to enrollment (Appendix E).
8. Recovered to CTCAE Grade 1 that are not considered a safety risk by the sponsor and investigator will be allowed.
9. Stable level of pain for at least one week before enrollment.
10. Absolute neutrophil count of >1.5 x 109/L and platelets >100 x 109/L.
11. Adequate blood chemistry parameters as defined by:
• Creatinine <1.7 mg/dL. If creatinine is >1.7 mg/dL, the calculated creatinine clearance must be >40 ml/min from the Cockcroft Gault or MDRD formulas (Appendix D).
• Bilirubin • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <1.5 x UNL if alkaline phosphatase >2.5 x ULN.
• AST and ALT <2.5 x ULN if alkaline phosphatase <2.5 ULN.
• Hemoglobin >10 g/dL.
12. Written and voluntary informed consent understood, signed and dated

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:
1. Prior chemotherapy or radioisotopes treatment for prostate cancer.
2. Prior anti IGF 1R and antibody based investigational therapies. Other investigational therapies (targeted or vaccine), unless otherwise agreed by investigators and sponsor, will require 4 weeks wash out period before enrollment.
3. Antiandrogen therapy (eg, flutamide) for primary cancer within 4 weeks prior to enrollment (6 weeks in the case of bicalutamide, nilutamide or other long acting anti androgens).
4. Radiation therapy to more than 25% of the bone marrow.
5. Local radiation within 2 weeks of enrollment.
6. Surgery within 4 weeks prior to study enrollment or not fully recovered from side effects of previous procedures.
7. Use of products known to affect PSA levels within 4 weeks of enrollment (eg, PC Calm, PC Plus, PC SPES, finasteride).
8. A serious uncontrolled medical disorder or active infection that would impair the ability to receive study treatment.
9. Significant active cardiac disease including: uncontrolled high blood pressure (ie, systolic blood pressure >160 mmHg, diastolic blood pressure >95 mm Hg), unstable angina, deep venous thrombosis, pulmonary embolism, cerebro vascular attack, valvular disease, congestive heart failure, myocardial infarction within the previous 6 months, or serious cardiac arrhythmias.
10. Subjects who are receiving chronic high dose immunosuppressive steroid therapy. Use of high dose corticosteroids within 2 weeks prior to enrollment (<100 mg prednisone per day or >40 mg dexamethasone per day). Previous steroid treatment is allowed but must be stopped at enrollment. Low dose steroid use for the control of nausea and vomiting (eg, dexamethasone 20 mg/day for up to 5 days) will be allowed. Topical steroid use is permitted. Inhaled steroids are permitted. Use of dexamethasone as pre medication is not an exclusion criterion.
11. Known severe hypersensitivity reactions to docetaxel or other drugs formulated in polysorbate 80.
12. Medical contraindication to any of the pre medications required priot to infusion.
13. Neuropathy greater than Grade 1 or evidence of unstable neurological symptoms within 4 weeks prior to enrollment.
14. No brain metastasis. Unevaluated central nervous system (CNS) symptoms suggestive of brain metastases within 2 weeks prior to enrollment. CNS symptoms must be evaluated with a computerized tomography (CT) scan or magnetic resonance imaging (MRI).
15. Dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
16. Subjects with reproductive potential who are not using adequate barrier methods on treatment.
17. Active malignancy other than prostate cancer within the past five years with the exception of non melanoma skin cancer (basal or squamous-cell skin cancer).



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

Health Condition(s) or Problem(s) studied

Metastatic hormone refractory (androgen indepedent) progressive prostate cancer (HRPC)
MedDRA version: 10.0 Level: LLT Classification code 10060862 Term:

Intervention(s)

Product Code: CP-751,871
Pharmaceutical Form: Solution for infusion
Current Sponsor code: CP-751,871
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: Taxotere
Product Name: Taxotere
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: docetaxel
CAS Number: 114977-28-5
Other descriptive name: Taxotere
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 20-80

Pharmaceutical Form: Gastro-resistant tablet
INN or Proposed INN: prednisone
CAS Number: 53-03-2
Other descriptive name: deltacotril
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Main Objective: Primary Objective:
• To assess the efficacy, in term of PSA response rate, of multiple doses of CP 751,871 in combination with docetaxel and prednisone in patients with HRPC.

Primary end point(s): PSA Response Rate

Secondary Objective: • To assess the safety and tolerability of multiple doses of CP 751,871 in combination with docetaxel and prednisone.
• To assess population PK of CP 751,871 when used in combination with docetaxel and prednisone.
• To evaluate the effect of CP-751,871 in combination with docetaxel and prednisone on biomarkers.
• To test for the occurrence of HAHA response to CP 751,871.
• Time to PSA progression, duration of PSA response, quality of life and management of pain will be investigated in an exploratory fashion (see Appendix A and B).

Secondary ID(s)

2005-002717-21-GB

A4021011