20070622

Amgen, Inc

One Amgen Center Drive, Thousand Oaks, CA, United States, 91320

IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com

IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com

No

No

No

Final

10 Sep 2015

No

Yes

07 Aug 2015

Yes

To determine if the treatment of rilotumumab in combination with ECX significantly improves overall survival (OS) as compared with rilotumumab-placebo in combination with ECX in subjects with unresectable, locally advanced or metastatic, mesenchymal epithelial transition factor (MET)-positive, gastric, or gastroesophageal junction (GEJ).

This study was conducted in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) and country-specific regulations/guidelines. The investigator was responsible for obtaining written informed consent from the subject or legally acceptable representative after adequate explanation of the aims, methods, anticipated benefits, and potential hazards of the study and before any protocol specified screening procedures or any investigational products are administered. The study protocol, amendments, and the informed consent form (ICF) were reviewed by the Institutional Review Boards (IRBs) and Independent Ethics Committees (IECs). No subjects were recruited into the study and no investigational product (IP) was shipped until the IRB/IEC gave written approval of the protocol and ICF and Amgen received copies of these approvals. An independent Data Monitoring Committee (DMC) external to Amgen conducted planned safety reviews and one interim efficacy review.

07 Nov 2012

Yes

Yes

Australia: 30

Austria: 8

Belgium: 6

Brazil: 21

Bulgaria: 16

Canada: 12

Czech Republic: 16

Denmark: 9

France: 20

Germany: 34

United Kingdom: 56

Greece: 10

Hungary: 16

Italy: 36

Mexico: 14

Poland: 47

Portugal: 17

Romania: 39

Russian Federation: 63

Slovakia: 7

South Africa: 4

Spain: 22

Sweden: 1

Switzerland: 7

Turkey: 14

Ukraine: 43

United States: 41

609

360

0

0

0

0

0

0

404

205

0

Overall Study (overall period)

Randomised - controlled

Yes

Placebo to rilotumumab

Solution for infusion

Intravenous use

Administered as an intravenous (IV) infusion through a peripheral line or indwelling catheter on day 1 of each cycle before dosing of ECX.

Epirubicin

Solution for infusion

Intravenous use

50 mg/m² IV on day 1 of every 21 day cycle.

Cisplatin

Concentrate for solution for infusion

Intravenous use

60 mg/m² IV on day 1 of every 21-day cycle

Capecitabine

Xeloda

Film-coated tablet

Oral use

625 mg/m² orally twice a day on days 1-21 of every 21 day cycle

Rilotumumab

AMG 102

Solution for infusion

Intravenous use

Administered as an intravenous (IV) infusion through a peripheral line or indwelling catheter on day 1 of each cycle before dosing of ECX.

Epirubicin

Solution for infusion

Intravenous use

50 mg/m² IV on day 1 of every 21 day cycle.

Cisplatin

Concentrate for solution for infusion

Intravenous use

60 mg/m² IV on day 1 of every 21-day cycle

Capecitabine

Xeloda

Film-coated tablet

Oral use

625 mg/m² orally twice a day on days 1-21 of every 21 day cycle

Placebo + ECX

Rilotumumab + ECX

Placebo + ECX

Rilotumumab + ECX

Overall survival (OS) is defined as the time from randomization to death due to any cause. Subjects who had not died by the analysis data cut-off or were lost to follow-up were censored at their last contact date, subjects who withdrew consent were censored at the date of withdrawal. OS was analyzed using Kaplan-Meier methods.

Primary

From randomization until the data cut-off date of 10 September 2015; median (min, max) follow-up time was 7.74 months (0.07, 32.69) in the rilotumumab arm and 9.36 months (0.13, 28.78) in the placebo arm.

A log-rank test stratified by the randomization factors was used for the primary comparison.

Placebo + ECX v Rilotumumab + ECX

609

Pre-specified

A Cox proportional hazards regression model was used to provide the hazard ratio and 2-sided 95% CI for rilotumumab + ECX relative to placebo + ECX, stratified by disease extent and ECOG performance status. A hazard ratio < 1.0 indicates a lower average event rate and a longer overall survival for Rilotumumab + ECX relative to Placebo + ECX.

Placebo + ECX v Rilotumumab + ECX

609

Pre-specified

1.339

2-sided

Progression-free survival (PFS) was defined as the time from the date of randomization to either disease progression or death. PFS was based upon the investigators assessment of disease progression, per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. If a subject’s disease did not progress and the subject was alive, PFS was censored at the last evaluable radiological assessment. If a subject had no tumor evaluation in the study, the PFS time was censored at the date of randomization. PFS was analyzed using Kaplan-Meier methods.

Secondary

From randomization until the data cut-off date of 10 September 2015; median (min, max) follow-up time was 7.74 months (0.07, 32.69) in the rilotumumab arm and 9.36 months (0.13, 28.78) in the placebo arm.

A log-rank test stratified by the randomization factors was used for the primary comparison.

Placebo + ECX v Rilotumumab + ECX

609

Pre-specified

The hazard ratio estimates were from a Cox proportional hazard model stratified by disease extent and ECOG performance status. A hazard ratio < 1.0 indicates a lower average event rate and a longer progression-free survival for Rilotumumab + ECX relative to Placebo + ECX.

Placebo + ECX v Rilotumumab + ECX

609

Pre-specified

1.256

2-sided

Survival rate at 12 months was defined as the stratified Kaplan-Meier (K-M) estimate of the percentage of subjects alive at 12 months.

Secondary

12 months

Placebo + ECX v Rilotumumab + ECX

609

Pre-specified

-8.9

2-sided

Time to progression (TTP) was defined as the time from the date of randomization to disease progression (per RECIST 1.1). If a subject’s disease did not progress, TTP was censored at the last evaluable radiological assessment, surgical resection date or the start of new anti-cancer therapy (if available) date. If a subject had no tumor evaluation in the study, the TTP time was censored at the date of randomization. If a subject died without radiological progression, TTP was censored at the last evaluable radiological assessment date. TTP was analyzed using Kaplan-Meier methods.

Secondary

From randomization until the data cut-off date of 10 September 2015; median (min, max) follow-up time was 7.74 months (0.07, 32.69) in the rilotumumab arm and 9.36 months (0.13, 28.78) in the placebo arm.

Placebo + ECX v Rilotumumab + ECX

609

Pre-specified

Placebo + ECX v Rilotumumab + ECX

609

Pre-specified

1.237

2-sided

Objective response rate was defined as the incidence rate of either complete response (CR) or partial response (PR) per RECIST 1.1 criteria. Best Overall Response for a subject is the best observed disease response per RECIST1.1, excluding tumor assessments after initiation of new anti-cancer therapy, surgical resection or an assessment of disease progression. Overall response was analyzed in the Response Analysis Set, defined as the subset of subjects in the Full Analysis Set with at least 1 uni-dimensionally measurable lesion at baseline, per RECIST 1.1.

Secondary

From randomization until the data cut-off date of 10 September 2015; median (min, max) follow-up time was 7.74 months (0.07, 32.69) in the rilotumumab arm and 9.36 months (0.13, 28.78) in the placebo arm.

A Cochran-Mantel–Haenszel test stratified by extent of disease and ECOG performance status was used to provide the adjusted common odds ratio.

Placebo + ECX v Rilotumumab + ECX

529

Pre-specified

0.53

2-sided

Disease control rate was defined as the incidence rate of either a CR, PR or stable disease (SD) per RECIST 1.1. The SD classification required subjects to have a response of SD ≥ 11 weeks after the date of the first dose of rilotumumab.

Secondary

From randomization until the data cut-off date of 10 September 2015; median (min, max) follow-up time was 7.74 months (0.07, 32.69) in the rilotumumab arm and 9.36 months (0.13, 28.78) in the placebo arm.

A Cochran-Mantel–Haenszel test stratified by extent of disease and ECOG performance status was used to provide the adjusted common odds ratio.

Placebo + ECX v Rilotumumab + ECX

529

Pre-specified

0.47

2-sided

Duration of response (DOR) was defined as time from the date of first response (PR or CR) to disease progression (per RECIST 1.1) or death. If a subject’s disease did not progress and the subject was alive, DOR was censored at the last evaluable radiological assessment. DOR was analyzed using Kaplan-Meier methods.

Secondary

From randomization until the data cut-off date of 10 September 2015; median (min, max) follow-up time was 7.74 months (0.07, 32.69) in the rilotumumab arm and 9.36 months (0.13, 28.78) in the placebo arm.

Time to initial response is calculated as the time from randomization to the first tumor response assessment with an outcome indicating an objective response (CR or PR) as classified by RECIST 1.1 criteria.

Secondary

From randomization until the data cut-off date of 10 September 2015; median (min, max) follow-up time was 7.74 months (0.07, 32.69) in the rilotumumab arm and 9.36 months (0.13, 28.78) in the placebo arm.

Secondary

From the date of first administration of protocol specified treatment through 30 days after the last administration of protocol specified treatment.

participants who were binding antibody positive post baseline with a negative or no result at baseline. The analysis was performed using the Antibody Analysis Set which includes all randomized subjects with evaluable antibody data.

Secondary

Day 1 of cycles 1, 3 & 7, and every 8 cycles thereafter (prior to study drug administration).

Secondary

Day 1 until end of treatment

Secondary

Cycle 1: Pre-dose, and within 5 min before end of infusion , 2 hours, 24 hours, 168 hours, and 336 hours after start of infusion and predose on day 1 of cycle 2

Secondary

Cycle 1 predose and within 5 minutes before end of infusion, 2 hours, 24 hours, 168 hours, and 336 hours after start of infusion and Cycle 2, predose on day 1

Secondary

Cycle 3 (week 7) day 1 predose to 24 hours post infusion

Secondary

Cycle 3

Median duration of exposure to study treatment was 3.7 months and 2.5 months for the placebo and rilotumumab arms respectively.

18.0

Placebo + ECX

Rilotumumab + ECX