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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00770848
• Other study ID #: 20070611
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 9, 2008
• Last updated: February 6, 2014
• Start date: November 2008
• Est. completion date: April 2012

Study information

• Verified date: February 2014
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Euorpean Union: Ethics CommitteeUnited States: Food and Drug AdministrationUnited States: Institutional Review BoardUnited States: Western Institutional Review BoardCanada: Health CanadaAustralia: National Health and Medical Research CouncilBelgium: Federal Agency for Medicinal Products and Health ProductsCzech Republic: State Institute for Drug ControlFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Sweden: Medical Products AgencyNetherlands: Ministry of Health, Welfare and Sport
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: April 2012
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Castrate-Resistant Prostate Cancer
• Mestastatic Prostate Cancer
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• AMG 102
Investigational product to be given at safe dose from phase 1b, will be administered by IV Q3W.
• AMG 102
Investigational product to be given at 15mg/kg, 7.5mg/kg, or 5mg/kg depending on assignment, will be administered by IV Q3W.
• Mitoxantrone
Administered Q3W for a maximum of 12 cyles
• Placebo
Placebo
• Prednisone
5 mg orally BID

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (2)

Oliner K.BM Ph2 CRPC.Journal-004521;

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	Phase 2 - Overall survival		Entire Study	Yes
Secondary	Phase 1b - Incidence of adverse events, abnormal laboratory values not defined as dose limiting toxicities		Treatment Period	Yes
Secondary	Phase 1b - Incidence of anti-AMG 102 antibody formation		Entire Study	Yes
Secondary	Phase 1b - Cmax and Cmin of AMG 102 concentration		Treatment Period	Yes
Secondary	Phase 2 - Progression-free survival		Entire Study	No
Secondary	Phase 2 - Maximum percentage reduction in PSA level		Entire Study	No
Secondary	Phase 2 - PSA response rate (=50% reduction in PSA values from baseline)		Entire Study	No
Secondary	Phase 2 - Objective response rate (CR and PR per RECIST with modifications)		Entire Study	No
Secondary	Phase 2 - Patient Report Outcome including pain-specific measures		Treatment Period	No
Secondary	Phase 2 - Incidence of adverse events and significant laboratory value changes from baseline		Treatment Period	Yes
Secondary	Phase 2 - Incidence of anti-AMG 102 antibody formation		Entire Study	Yes
Secondary	Phase 2 - Cmax and Cmin of AMG 102; Cmax and AUC for Mitoxantrone		Treatment Period	Yes
Secondary	Phase 2 - Percentage change in PSA levels from baseline to 12 weeks (or earlier for those who discontinue therapy)		Treatment Period	No

External Links

•   AmgenTrials clinical trials website