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

Primary Purpose

Cancer, Castrate-Resistant Prostate Cancer, Mestastatic Prostate Cancer

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

AMG 102

Mitoxantrone

Placebo

Prednisone

About this trial

This is an interventional treatment trial for Cancer focused on measuring CRPC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Experimental

Placebo Comparator

Experimental

Arm Label

Phase 1b - AMG 102

Phase 2 Arm A - AMG 102 + MP

Phase 2 Arm C- PLACEBO

Phase 2 Arm B - AMG 102 + MP

Arm Description

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.

AMG 102 safe dose level in phase 1b in combination with MP, will be administered by IV Q3W.

Placebo in combination with MP, will be administered by IV Q3W.

Safe dose level in phase 1b of AMG 102 + MP will be administered by Q3W

Outcomes

Primary Outcome Measures

Phase 1b - Incidence of adverse events defined by dose-limiting toxicities

Phase 2 - Overall survival

Secondary Outcome Measures

Phase 1b - Incidence of adverse events, abnormal laboratory values not defined as dose limiting toxicities

Phase 1b - Incidence of anti-AMG 102 antibody formation

Phase 1b - Cmax and Cmin of AMG 102 concentration

Phase 2 - Progression-free survival

Phase 2 - Maximum percentage reduction in PSA level

Phase 2 - PSA response rate (≥50% reduction in PSA values from baseline)

Phase 2 - Objective response rate (CR and PR per RECIST with modifications)

Phase 2 - Patient Report Outcome including pain-specific measures

Phase 2 - Incidence of adverse events and significant laboratory value changes from baseline

Phase 2 - Incidence of anti-AMG 102 antibody formation

Phase 2 - Cmax and Cmin of AMG 102; Cmax and AUC for Mitoxantrone

Phase 2 - Percentage change in PSA levels from baseline to 12 weeks (or earlier for those who discontinue therapy)

Full Information

NCT ID

NCT00770848

First Posted

October 9, 2008

Last Updated

February 6, 2014

Sponsor

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT00770848

Brief Title

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

2. Study Status

Record Verification Date

February 2014

Overall Recruitment Status

Completed

Study Start Date

November 2008 (undefined)

Primary Completion Date

January 2011 (Actual)

Study Completion Date

April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

4. Oversight

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cancer, Castrate-Resistant Prostate Cancer, Mestastatic Prostate Cancer, Prostate Cancer

Keywords

CRPC

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

162 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase 1b - AMG 102

Arm Type

Other

Arm Description

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.

Arm Title

Phase 2 Arm A - AMG 102 + MP

Arm Type

Experimental

Arm Description

AMG 102 safe dose level in phase 1b in combination with MP, will be administered by IV Q3W.

Arm Title

Phase 2 Arm C- PLACEBO

Arm Type

Placebo Comparator

Arm Description

Placebo in combination with MP, will be administered by IV Q3W.

Arm Title

Phase 2 Arm B - AMG 102 + MP

Arm Type

Experimental

Arm Description

Safe dose level in phase 1b of AMG 102 + MP will be administered by Q3W

Intervention Type

Drug

Intervention Name(s)

AMG 102

Other Intervention Name(s)

Rilotumumab

Intervention Description

Investigational product to be given at safe dose from phase 1b, will be administered by IV Q3W.

Intervention Type

Drug

Intervention Name(s)

AMG 102

Other Intervention Name(s)

Rilotumumab

Intervention Description

Investigational product to be given at 15mg/kg, 7.5mg/kg, or 5mg/kg depending on assignment, will be administered by IV Q3W.

Intervention Type

Drug

Intervention Name(s)

Mitoxantrone

Intervention Description

Administered Q3W for a maximum of 12 cyles

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Prednisone

Intervention Description

5 mg orally BID

Primary Outcome Measure Information:

Title

Phase 1b - Incidence of adverse events defined by dose-limiting toxicities

Time Frame

21 days after the 6th subjects has recieved 1st cycle of AMG 102 in combination with MP

Title

Phase 2 - Overall survival

Time Frame

Entire Study

Secondary Outcome Measure Information:

Title

Phase 1b - Incidence of adverse events, abnormal laboratory values not defined as dose limiting toxicities

Time Frame

Treatment Period

Title

Phase 1b - Incidence of anti-AMG 102 antibody formation

Time Frame

Entire Study

Title

Phase 1b - Cmax and Cmin of AMG 102 concentration

Time Frame

Treatment Period

Title

Phase 2 - Progression-free survival

Time Frame

Entire Study

Title

Phase 2 - Maximum percentage reduction in PSA level

Time Frame

Entire Study

Title

Phase 2 - PSA response rate (≥50% reduction in PSA values from baseline)

Time Frame

Entire Study

Title

Phase 2 - Objective response rate (CR and PR per RECIST with modifications)

Time Frame

Entire Study

Title

Phase 2 - Patient Report Outcome including pain-specific measures

Time Frame

Treatment Period

Title

Phase 2 - Incidence of adverse events and significant laboratory value changes from baseline

Time Frame

Treatment Period

Title

Phase 2 - Incidence of anti-AMG 102 antibody formation

Time Frame

Entire Study

Title

Phase 2 - Cmax and Cmin of AMG 102; Cmax and AUC for Mitoxantrone

Time Frame

Treatment Period

Title

Phase 2 - Percentage change in PSA levels from baseline to 12 weeks (or earlier for those who discontinue therapy)

Time Frame

Treatment Period

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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: 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 progression according to RECIST criteria for measurable lesions, or 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Organizational Affiliation

Amgen

Official's Role

Study Director

12. IPD Sharing Statement

Citations:

Citation

Oliner K.BM Ph2 CRPC.Journal-004521;

Results Reference

background

PubMed Identifier

23136195

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.

Results Reference

background

Links:

URL

http://www.amgentrials.com

Description

AmgenTrials clinical trials website

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

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