20090508

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

16 Dec 2016

No

Yes

16 Dec 2016

No

The primary objective of this study was to determine if paclitaxel plus trebananib is superior to paclitaxel plus placebo, as measured by progression-free survival (PFS), defined as the time from randomization to the earliest of the dates of first radiologic disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) with modifications or death from any cause, in subjects with recurrent partially platinum-sensitive or -resistant epithelial ovarian, primary peritoneal, or fallopian tube cancers.

This study was conducted in accordance with United States Food and Drug Administration (FDA) regulations/guidelines set forth in 21 CFR Parts 11, 50, 54, 56, and 312 and International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines. All subjects provided written informed consent before undergoing any study-related procedures, including screening procedures. 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.

10 Nov 2010

Yes

Yes

Canada: 104

United States: 80

Australia: 20

Belgium: 14

France: 110

Greece: 38

Italy: 53

Portugal: 13

Spain: 104

Sweden: 10

Switzerland: 11

United Kingdom: 9

Brazil: 11

Bulgaria: 8

Chile: 11

Croatia: 3

Czech Republic: 9

Estonia: 6

Hong Kong: 3

India: 27

Israel: 15

Japan: 57

Korea, Republic of: 28

Latvia: 25

Malaysia: 11

Mexico: 20

Peru: 6

Poland: 34

Romania: 7

Russian Federation: 56

Slovenia: 5

South Africa: 11

919

448

0

0

0

0

0

0

651

268

0

Overall Study (overall period)

Randomised - controlled

Yes

Placebo

Powder for solution for infusion

Intravenous use

Administered as an IV infusion via an infusion pump or gravity over 30 to 60 minutes once a week.

Paclitaxel

Taxol®

Concentrate for solution for infusion

Intravenous use

Administered as an IV infusion over 1 hour on weeks 1, 2, and 3 of each 4-week cycle.

Trebananib

AMG 386

Powder for solution for infusion

Intravenous use

Administered as an IV infusion via an infusion pump or gravity over 30 to 60 minutes once a week.

Paclitaxel

Taxol®

Concentrate for solution for infusion

Intravenous use

Administered as an IV infusion over 1 hour on weeks 1, 2, and 3 of each 4-week cycle.

Placebo

Trebananib

Placebo

Trebananib

Progression-free survival (PFS) is defined as the time from the date of randomization to the earliest of the dates of first objective disease progression or death from any cause. The determination of radiologic disease progression was based on investigator assessments, per RECIST 1.1 with modifications. Participants not meeting PFS criteria by the analysis data cutoff date were censored at their last evaluable radiologic disease assessment date. Events of radiographic progression per RECIST 1.1 with modifications that occurred after initiation of subsequent anticancer therapy were not considered PFS events and were censored at the last evaluable radiographic tumor assessment prior to initiation of subsequent anticancer therapy. Deaths occurring after initiation of subsequent anticancer therapy were considered PFS events.

Primary

From randomization to the data cut-off date; median follow-up time was 17.7 months.

Placebo v Trebananib

919

Pre-specified

0.72

2-sided

Overall survival was a key secondary endpoint and was defined as the time from the randomization date to the date of death from any cause. Subjects known to be alive prior to the data cutoff date were censored at the last contact prior to the cutoff date. Subjects known to be alive or dead after the data cutoff date were censored at the data cutoff date.

Secondary

From randomization to the data cut-off date; median follow-up time was 17.7 months.

Placebo v Trebananib

919

Pre-specified

1.03

2-sided

Objective response rate (ORR) was defined as the incidence of either a complete response (CR) or partial response (PR) while on study, as defined in RECIST 1.1 with modifications. Confirmation for PR and CR was not required. All subjects who did not meet the criteria for objective response by the analysis cutoff date were considered non-responders. Only subjects with measurable disease at baseline were included in the analysis of ORR.

Secondary

From randomization to the data cut-off date; median follow-up time was 17.7 months.

Placebo v Trebananib

869

Pre-specified

1.465

2-sided

Duration of response (DOR) was defined as the time from the first objective response to disease progression per RECIST 1.1 with modifications or death due to any cause. Subjects not meeting criteria for disease progression per RECIST 1.1 with modifications by the analysis data cutoff date were censored at their last evaluable disease assessment date. The analysis of DOR was conducted on the subset of subjects with measurable disease at baseline who experienced an objective response during the study.

Secondary

From randomization to the data cut-off date; median follow-up time was 17.7 months.

CA-125 is a tumor marker to monitor response to treatment and recurrence in ovarian cancer. CA-125 response was evaluated as a secondary endpoint among subjects with baseline CA-125 ≥ 2 x upper limit of normal (ULN) and was defined as a ≥ 50% reduction in CA-125 levels from baseline according to the Gynecologic Cancer Intergroup (GCIG) criteria. All subjects evaluable for CA-125 response that did not meet the criteria for a CA-125 response were considered non-responders.

Secondary

From randomization to the data cut-off date; median follow-up time was 17.7 months.

Placebo v Trebananib

737

Pre-specified

1.3943

2-sided

Adverse events (AEs) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Trebananib/placebo-related or paclitaxel-related adverse events are those events for which the investigator considered there to be a reasonable possibility that the event may have been caused by the study treatment, trebananib/placebo or paclitaxel, respectively. Participants are analyzed according to treatment actually received.

Secondary

From first dose of any study drug up to 30 days after the last dose; median duration was 134 days for placebo and 156 days for trebananib.

Secondary

Weeks 1 and 5 at the end of infusion

Secondary

Weeks 2, 5 and 9, predose

Blood samples were tested for anti-trebananib binding antibodies using a validated biosensore Biacore® immunoassay. Samples with positive binding antibody results were further tested for the neutralizing activity of the antibody using a validated electrochemiluminescence receptor-binding assay. Participants were considered positive for developing antibodies if they had a negative or no result at baseline and a positive result post-baseline.

Secondary

Day 1 of weeks 1 and 9 and 30 days after last dose

The FACT-O evaluates the health-related quality of life (HRQOL) and symptoms in patients with ovarian cancer. It consists of the FACT-G, a 27 item general cancer questionnaire and a 12-item ovarian cancer-specific subscale (OCS). Each item is scored by the participant on a scale from 0 (not at all true) to 4 (very much true). The total score ranges from 0 to 156; a higher total score indicates better quality of life or less severe symptoms. The patient-reported outcomes (PRO) analysis set is defined as a subset of randomized subjects who have a baseline PRO assessment and at least one post-baseline PRO assessment prior to disease progression

Secondary

Baseline and Weeks 5, 9, 13, 17, 25, 33, 41, 49, 57, 65, 73, 81, and the safety follow-up visit 30 days after last dose.

The FACT-O evaluates the health-related quality of life (HRQOL) and symptoms in patients with ovarian cancer. It consists of the FACT-G, a 27 item general cancer questionnaire and a 12-item ovarian cancer-specific subscale (OCS). The OCS consists of 12 symptom items including swelling in stomach area, cramps in stomach area, weight loss, hair loss, control of bowels, appetite, vomiting, ability to get around, liking the appearance of one’s body, being able to feel like a woman, interest in sex, and concern about ability to have children. Each item is scored by the participant on a scale from 0 (not at all true) to 4 (very much true). The OCS summary score ranges from 0 to 48, where a higher score indicates better quality of life or less severe symptoms. The PRO analysis set includes a subset of randomized subjects who had a baseline PRO assessment and at least one post-baseline PRO assessment prior to disease progression.

Secondary

Baseline and Weeks 5, 9, 13, 17, 25, 33, 41, 49, 57, 65, 73, 81, and the safety follow-up visit 30 days after last dose.

The EQ-5D is a standardized instrument for use as a generic, preference-based measure of health outcome. The EQ-5D questionnaire captures two basic types of information, a descriptive “profile,” or “health state,” and an overall health rating using a visual analogue scale. The health state includes five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each question has 3 answer choices: 1 (no problems), 2 (moderate problems), and 3 (extreme problems). The health states for each respondent are converted into a single index number using a specified set of weights. Resulting scores can range from 1.0 and –0.594. A higher score indicates a more preferred health status with 1.0 representing perfect health. The PRO analysis set includes a subset of randomized subjects who had a baseline assessment and at least 1 post-baseline PRO assessment prior to disease progression.

Secondary

Baseline and Weeks 5, 9, 13, 17, 25, 33, 41, 49, 57, 65, 73, 81, and the safety follow-up visit 30 days after last dose.

The EQ-5D is a standardized instrument for use as a generic, preference-based measure of health outcome. The EQ-5D questionnaire captures two basic types of information, a descriptive “profile,” or “health state,” and an overall health rating using a visual analogue scale (VAS). The visual analogue scale asks respondents to rate their present health status on a 0 - 100 visual analogue scale, with 0 labeled as “Worst imaginable health state” and 100 labeled as “Best imaginable health state.” The VAS score is determined by observing the point at which the subjects hand drawn line intersects the scale. The PRO analysis set includes the subset of randomized subjects who had a baseline assessment and at least 1 post-baseline PRO assessment prior to disease progression.

Secondary

Baseline and Weeks 5, 9, 13, 17, 25, 33, 41, 49, 57, 65, 73, 81, and the safety follow-up visit 30 days after last dose.

From first dose of any study drug until 30 days after last dose. Median duration was 134 days for placebo and 156 days for trebananib.

Five subjects (3 randomized to trebananib and 2 randomized to placebo) received at least 1 incorrect dose of investigational product during the study. These subjects are characterized in the safety population under the treatment they actually received rather than the treatment they were randomized to receive.

19.1

Placebo + Paclitaxel

Trebananib + Paclitaxel