A Phase 1b/2 Study to Assess the Safety and Efficacy of AMG 102 in Combination withMitoxantrone and Prednisone in Subjects with Previously Treated Castrate Resistant Prostate Cancer

Conditions: Previously Treated Castrate Resistant Prostate Cancer
MedDRA version: 9.1Level: LLTClassification code 10060862Term: Prostate cancer

Registration Number: EUCTR2008-004355-30-GB

Lead Sponsor: Amgen Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: 162

Inclusion Criteria

Disease-related
• Pathologically confirmed adenocarcinoma of the prostate
• Radiographic evidence of metastatic disease
• Progressive disease meeting at least one of the following criteria:
1) a sequence of at least 2 rising PSA values measured at a minimum of 1 week apart with a 2 ng/mL minimum starting value, or
2) progression according to RECIST criteria for measurable lesions, or
3) appearance of 2 or more new lesions on bone scan.
• History of prior taxane-based chemotherapy for metastatic prostate cancer; no more than one prior chemotherapy regimen for CRPC is allowed (estramustine will be considered as chemotherapy)
• ECOG Performance status 0 or 1
• Life expectancy = 3 months
Demographic
Men = 18 years of age
Laboratory
• Castrate levels of serum testosterone (< 50 ng/dL)
• PSA = 2 ng/mL
• Hemoglobin = 9 g/dL (can be post-transfusion)
• Absolute neutrophil count = 1.5 x 109/L
• Platelet count = 100 x 109/L (without transfusion within 14 days before enrollment or randomization)
• Creatinine = 2X ULN
• Aspartate aminotransferase (AST) and alanine amino transferase (ALT) = 3.0 x ULN
• Total bilirubin = 1.5x ULN
• Partial thromboplastin time (PTT) = 1.5 x ULN and international normalized ratio (INR) = ULN.
Medications
For patients without a history of surgical castration, continued GnRH analog administration is required
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

Disease-related
• Treatment with external beam radiotherapy = 14 days before enrollment or radiopharmaceutical =8 weeks
• = 4 weeks since receipt of most recent prior chemotherapy, non-GnRH analog hormonal therapy (except for continuing corticosteroids) or other systemic therapy to treat prostate cancer and <6 weeks since receipt of prior bevacizumab. Patients with evidence of an antiandrogen withdrawal response must demonstrate objective or PSA progression following the response.
• Known CNS metastases (epidural disease is allowed if it has been treated and there is no progression in the treated area).
Cardiac
• Significant cardiovascular disease (CHF class III or IV, uncontrolled angina, MI within 6 months of enrollment); patients with medically stable atrial fibrillation may be included.
• LVEF < 50% by MUGA or ECHO
Medications
• Treatment of infection with systemic anti-infectives within 7 days before enrollment (with the exception of uncomplicated urinary tract infection)
• Concurrent or prior (within 7 days of enrollment) anticoagulation therapy, except that use of low dose coumarin-type anticoagulants or heparins for prophylaxis against central venous catheter thrombosis is allowed
General
• Major surgical procedure = 30 days before enrollment or not yet recovered from prior major surgery
• Minor surgery =14 days before enrollment or not yet recovered from prior minor surgery; central venous catheter placement is allowed at any time prior to enrollment provided that patient has recovered and any surgical wound has healed
• Any prior or synchronous malignancy (except for non-melanomatous skin cancer or lentigo maligna) other than the study disease, unless treated with curative intent with no evidence of disease = 3 years before enrollment
• Presence of peripheral neuropathy > Grade 1
• Presence of peripheral edema > Grade 2
• Known proteinuria > 1 gram/day (subjects with >2+ protein on screening urinalysis require a quantitative evaluation of urine protein)
• Any clinically significant medical condition other than cancer, including cardiovascular disease or COPD, which in the opinion of the investigator would interfere with the safe delivery of study treatment or increase risk of toxicity
• History of any medical condition that in the opinion of the investigator, may increase the risks associated with study participation or study treatments or may interfere with the conduct of the study or interpretation of study results
• Known positive test for HIV, hepatitis C, chronic or active hepatitis B
• Serious or non-healing wound
• Unable to begin protocol specified treatment within 7 days after enrollment
• Other investigational procedures are excluded.
• Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s).
• Treated previously with c-Met or HGF targeted therapy
• Subject is not using adequate contraceptive precautions.
• Subject has known sensitivity to any of the products to be administered during dosing.
• Subject will not be available for follow-up assessment.
• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.