AMG 102 in Combination With Mitoxantrone and Prednisone in Subjects With Previously Treated Castrate Resistant Prostate Cancer

Phase 1

Completed

Conditions: Cancer
Castrate-Resistant Prostate Cancer
Mestastatic Prostate Cancer
Prostate Cancer

Interventions: Drug: AMG 102
Drug: Placebo
Drug: Mitoxantrone
Drug: Prednisone

Registration Number: NCT00770848

Lead Sponsor: Amgen

Brief Summary: The primary objectives of this study are the following:

Phase 1b: To identify a safe dose level of AMG 102, up to 15 mg/kg Q3W, to combine with mitoxantrone and prednisone (MP) Phase 2: To estimate with adequate precision the effect of the addition of AMG 102 to MP, compared with placebo plus MP, as assessed by the hazard ratio (HR) for overall survival (OS) of previously treated subjects with castrate-resistant prostate cancer (CRPC)

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 162

Inclusion Criteria

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
For patients without a history of surgical castration, continued GnRH analog administration is required
ECOG Performance status of 0 or 1
Life expectancy ≥ 3 months

Exclusion Criteria

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.
Known CNS metastases (epidural disease is allowed if it has been treated and there is no progression in the treated area).
Significant cardiovascular disease
LVEF < 50% by MUGA or ECHO
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
Major surgical procedure ≤30 days before enrollment or not yet recovered from prior major surgery
Presence of peripheral edema > Grade 2
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2 Arm C- PLACEBO	Placebo	Placebo in combination with MP, will be administered by IV Q3W.
Phase 2 Arm A - AMG 102 + MP	AMG 102	AMG 102 safe dose level in phase 1b in combination with MP, will be administered by IV Q3W.
Phase 2 Arm A - AMG 102 + MP	Mitoxantrone	AMG 102 safe dose level in phase 1b in combination with MP, will be administered by IV Q3W.
Phase 1b - AMG 102	Mitoxantrone	Phase 1b is an open-label study with AMG 102 at 15mg/kg de-escalating to 7.5mg/kg and 5mg/kg if needed, will be administered by IV Q3W in combination with MP.
Phase 1b - AMG 102	Prednisone	Phase 1b is an open-label study with AMG 102 at 15mg/kg de-escalating to 7.5mg/kg and 5mg/kg if needed, will be administered by IV Q3W in combination with MP.
Phase 2 Arm A - AMG 102 + MP	Prednisone	AMG 102 safe dose level in phase 1b in combination with MP, will be administered by IV Q3W.
Phase 2 Arm C- PLACEBO	Mitoxantrone	Placebo in combination with MP, will be administered by IV Q3W.
Phase 2 Arm C- PLACEBO	Prednisone	Placebo in combination with MP, will be administered by IV Q3W.
Phase 2 Arm B - AMG 102 + MP	AMG 102	Safe dose level in phase 1b of AMG 102 + MP will be administered by Q3W
Phase 2 Arm B - AMG 102 + MP	Mitoxantrone	Safe dose level in phase 1b of AMG 102 + MP will be administered by Q3W
Phase 2 Arm B - AMG 102 + MP	Prednisone	Safe dose level in phase 1b of AMG 102 + MP will be administered by Q3W
Phase 1b - AMG 102	AMG 102	Phase 1b is an open-label study with AMG 102 at 15mg/kg de-escalating to 7.5mg/kg and 5mg/kg if needed, will be administered by IV Q3W in combination with MP.

Primary Outcome Measures

Name	Time	Method
Phase 1b - Incidence of adverse events defined by dose-limiting toxicities	21 days after the 6th subjects has recieved 1st cycle of AMG 102 in combination with MP
Phase 2 - Overall survival	Entire Study

Secondary Outcome Measures

Name	Time	Method
Phase 1b - Incidence of adverse events, abnormal laboratory values not defined as dose limiting toxicities	Treatment Period
Phase 1b - Incidence of anti-AMG 102 antibody formation	Entire Study
Phase 1b - Cmax and Cmin of AMG 102 concentration	Treatment Period
Phase 2 - Progression-free survival	Entire Study
Phase 2 - Maximum percentage reduction in PSA level	Entire Study
Phase 2 - PSA response rate (≥50% reduction in PSA values from baseline)	Entire Study
Phase 2 - Objective response rate (CR and PR per RECIST with modifications)	Entire Study
Phase 2 - Patient Report Outcome including pain-specific measures	Treatment Period
Phase 2 - Incidence of adverse events and significant laboratory value changes from baseline	Treatment Period
Phase 2 - Incidence of anti-AMG 102 antibody formation	Entire Study
Phase 2 - Cmax and Cmin of AMG 102; Cmax and AUC for Mitoxantrone	Treatment Period
Phase 2 - Percentage change in PSA levels from baseline to 12 weeks (or earlier for those who discontinue therapy)	Treatment Period