Clinical trial NCT00770848: AMG 102 in Combination With Mitoxantrone and Prednisone in Subjects With Previously Treated Castrate Resistant Prostate Cancer
Official title: A Phase 1b/2 Study to Assess the Safety and Efficacy of AMG 102 in Combination With Mitoxantrone and Prednisone in Subjects With Previously Treated Castrate Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cancer
Castrate-Resistant Prostate Cancer
Mestastatic Prostate Cancer
Prostate Cancer
Keywords: CRPC
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2008-10-10
Enrollment: 162
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1b - Incidence of adverse events defined by dose-limiting toxicities
timeFrame: 21 days after the 6th subjects has recieved 1st cycle of AMG 102 in combination with MP
measure: Phase 2 - Overall survival
timeFrame: Entire Study
Secondary outcomes:
measure: Phase 1b - Incidence of adverse events, abnormal laboratory values not defined as dose limiting toxicities
timeFrame: Treatment Period
measure: Phase 1b - Incidence of anti-AMG 102 antibody formation
timeFrame: Entire Study
measure: Phase 1b - Cmax and Cmin of AMG 102 concentration
timeFrame: Treatment Period
measure: Phase 2 - Progression-free survival
timeFrame: Entire Study
measure: Phase 2 - Maximum percentage reduction in PSA level
timeFrame: Entire Study
measure: Phase 2 - PSA response rate (≥50% reduction in PSA values from baseline)
timeFrame: Entire Study
measure: Phase 2 - Objective response rate (CR and PR per RECIST with modifications)
timeFrame: Entire Study
measure: Phase 2 - Patient Report Outcome including pain-specific measures
timeFrame: Treatment Period
measure: Phase 2 - Incidence of adverse events and significant laboratory value changes from baseline
timeFrame: Treatment Period
measure: Phase 2 - Incidence of anti-AMG 102 antibody formation
timeFrame: Entire Study
measure: Phase 2 - Cmax and Cmin of AMG 102; Cmax and AUC for Mitoxantrone
timeFrame: Treatment Period
measure: Phase 2 - Percentage change in PSA levels from baseline to 12 weeks (or earlier for those who discontinue therapy)
timeFrame: Treatment Period
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Oliner K.BM Ph2 CRPC.Journal-004521;
citation: Ryan CJ, Rosenthal M, Ng S, Alumkal J, Picus J, Gravis G, Fizazi K, Forget F, Machiels JP, Srinivas S, Zhu M, Tang R, Oliner KS, Jiang Y, Loh E, Dubey S, Gerritsen WR. Targeted MET inhibition in castration-resistant prostate cancer: a randomized phase II study and biomarker analysis with rilotumumab plus mitoxantrone and prednisone. Clin Cancer Res. 2013 Jan 1;19(1):215-24. doi: 10.1158/1078-0432.CCR-12-2605. Epub 2012 Nov 7.