A Phase 1 Study of AMG 211 in Participants With Advanced... | NCT02291614

NCT02291614

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2014-000201-12	EudraCT Number

Status Module

Sponsor/Collaborators Module

Name	Class
MedImmune LLC	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
AMG 211 200 μg/day for 7/14 Days	Experimental	In cycle 1 participants receive 200 µg/day AMG 211 administered as a continuous intravenous infusion (cIV) infusion at a constant flow rate for 7 days followed by a 3-week treatment-free interval. In cycle 2 and thereafter, participants receive 200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.	Drug: AMG 211
AMG 211 200 μg/day for 14 Days	Experimental	Participants receive 200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.	Drug: AMG 211
AMG 211 400 μg/day for 14 Days	Experimental	Participants receive 400 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.	Drug: AMG 211
AMG 211 800 μg/day for 14 Days	Experimental	Participants receive 800 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.	Drug: AMG 211
AMG 211 1600 μg/day for 14 Days	Experimental	Participants receive 1600 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
AMG 211	Drug	continuous intravenous infusion (cIV) infusion in cycles from 7 to 28 days	AMG 211 12,800 µg/day for 28 Days AMG 211 1600 µg/day for 28 Days

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Dose-Limiting Toxicities (DLTs)	A DLT was defined as any of the following occurring during the first 28 days of treatment and regarded by the investigator and/or sponsor as related to AMG 211. Hematological DLTs: absolute neutrophil count (ANC) < 0.5 × 10⁹ cells/L for ≥ 7 days; febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infection) with ANC < 0.5 × 10⁹ cells/L and fever ≥ 38.5°C; platelets < 25 × 10⁹ cells/L ≥ 7 days. Non-hematological DLTs: any AMG 211-related ≥ grade 3 non-hematological toxicity, excluding nausea and vomiting not refractory to anti-emetics, flare-up of pain due to potential increase in tumor volume, cytokine release syndrome manageable with symptomatic treatment and/or infusion interruption of up to 2 days. The Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was used to assess toxicities/adverse events.	28 days
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence, which does not necessarily have a causal relationship with study treatment. A serious adverse event (SAE) was defined as an event that: was fatal or life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/borth defect; or other significant medical event. A TEAE was defined as any AE starting on or after the first dose of study drug and up to and including 30 days after the end of last dose of study drug. The severity of each adverse event was graded using CTCAE version 4.03 criteria (1=mild, 2=moderate, 3=severe, 4=life-threatining, 5=death). 'Any TEAE' includes both serious and non-serious TEAEs.	From first dose of study drug through end of treatment + 30 days (median time frame was 75.5 days).

Secondary Outcomes

Measure	Description	Time Frame
Maximum Observed Concentration (Cmax) of AMG 211 in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days	Levels of AMG 211 in plasma samples collected during this study were analyzed using an electrochemiluminiscence assay. The lower limit of quantification (LLOQ) of the assay was 0.10 ng/mL.	Cycle 1: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Hamburg		20246	Germany
Research Site

References Module

Label	URL
AmgenTrials clinical trials website	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

This study was to be conducted in 2 parts: dose-escalation and dose-expansion (planned to enroll additional participants to gain further clinical experience with AMG 211). The dose expansion part was not conducted (study terminated early). In the dose-escalation cohorts, participants were assigned sequentially into cohorts as they opened.

Arm/Group Information

ID	Title	Description
FG000	AMG 211 200 µg/Day for 7/14 Days	In cycle 1 participants received 200 µg/day AMG 211 administered as a continuous intravenous (cIV) infusion at a constant flow rate for 7 days followed by a 3-week treatment-free interval. In cycle 2 and thereafter, participants received 200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
FG001	AMG 211 200 µg/Day for 14 Days	Participants received 200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
FG002	AMG 211 400 µg/Day for 14 Days	Participants received 400 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
FG003	AMG 211 800 µg/Day for 14 Days	Participants received 800 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
FG004	AMG 211 1600 µg/Day for 14 Days	Participants received 1600 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
FG005	AMG 211 1600 µg/Day for 28 Days	Participants received 1600 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval.
FG006	AMG 211 3200 µg/Day for 14 Days	Participants received 3200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
FG007	AMG 211 3200 µg/Day for 28 Days	Participants received 3200 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval.
FG008	AMG 211 6400 µg/Day for 14 Days	Participants received 6400 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
FG009	AMG 211 6400 µg/Day for 28 Days	Participants received 6400 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval.
FG010	AMG 211 12,800 µg/Day for 28 Days	Participants received 12,800 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0003 subjects FG0013 subjects FG0023 subjects FG0035 subjects FG0043 subjects FG0053 subjects FG0066 subjects FG0073 subjects FG0083 subjects FG00911 subjects FG0102 subjects
Received AMG 211		FG0003 subjects FG0013 subjects FG0023 subjects FG0035 subjects FG004
COMPLETED		FG0003 subjects FG0012 subjects FG0022 subjects FG0034 subjects FG004
NOT COMPLETED		FG0000 subjects FG0011 subjects FG0021 subjects FG0031 subjects FG004

Type	Comment	Reasons
Lost to Follow-up		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	AMG 211 200 µg/Day for 7/14 Days	In cycle 1 participants received 200 µg/day AMG 211 administered as a cIV infusion at a constant flow rate for 7 days followed by a 3-week treatment-free interval. In cycle 2 and thereafter, participants received 200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Dose-Limiting Toxicities (DLTs)

A DLT was defined as any of the following occurring during the first 28 days of treatment and regarded by the investigator and/or sponsor as related to AMG 211. Hematological DLTs: absolute neutrophil count (ANC) < 0.5 × 10⁹ cells/L for ≥ 7 days; febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infection) with ANC < 0.5 × 10⁹ cells/L and fever ≥ 38.5°C; platelets < 25 × 10⁹ cells/L ≥ 7 days. Non-hematological DLTs: any AMG 211-related ≥ grade 3 non-hematological toxicity, excluding nausea and vomiting not refractory to anti-emetics, flare-up of pain due to potential increase in tumor volume, cytokine release syndrome manageable with symptomatic treatment and/or infusion interruption of up to 2 days. The Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was used to assess toxicities/adverse events.

Safety Analysis Set: all participants who enrolled and received at least one dose of AMG 211. Participants were evaluable for a DLT if they received at least 90% of planned doses in the first treatment cycle.

Posted

Count of Participants

Participants

28 days

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	AMG 211 200 µg/Day for 7/14 Days	In cycle 1 participants received 200 µg/day AMG 211 administered as a cIV infusion at a constant flow rate for 7 days followed by a 3-week treatment-free interval. In cycle 2 and thereafter, participants received 200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Study Director	Amgen Inc.	866-572-6436		medinfo@amgen.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 10, 2016	Sep 30, 2020	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Mar 19, 2020	Sep 30, 2020	SAP_001.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D009369	Neoplasms

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

AMG 211 1600 μg/day for 14 Days

AMG 211 200 μg/day for 14 Days

AMG 211 200 μg/day for 7/14 Days

AMG 211 3200 µg/day for 14 Days

AMG 211 3200 µg/day for 28 Days

AMG 211 400 μg/day for 14 Days

AMG 211 6400 µg/day for 14 Days

AMG 211 6400 µg/day for 28 Days

AMG 211 800 μg/day for 14 Days

EG0000 affected3 at risk

EG0010 affected3 at risk

EG0020 affected3 at risk

EG0032 affected5 at risk

EG0040 affected3 at risk

EG0050 affected3 at risk

EG0061 affected6 at risk

EG0071 affected3 at risk

EG0080 affected3 at risk

EG0090 affected10 at risk

EG0100 affected2 at risk

EG0001 affected3 at risk

EG0011 affected3 at risk

EG0020 affected3 at risk

EG0032 affected5 at risk

EG0040 affected3 at risk

EG0051 affected3 at risk

EG0060 affected6 at risk

EG0070 affected3 at risk

EG0080 affected3 at risk

EG0091 affected10 at risk

EG0101 affected2 at risk

OG00319.8± 3.67(3.67 to )

OG00455.1± 11.0(11.0 to )

OG005116± 32.4(32.4 to )

OG006129± 51.0(51.0 to )

OG003398± 99999(99999 to )

OG003214± 77.5(77.5 to )

OG004617± 186(186 to )

OG0051540± 936(936 to )

OG0061420± 666(666 to )

OG0036080± 99999(99999 to )

OG003215± 77.5(77.5 to )

OG004619± 186(186 to )

OG0051540± 938(938 to )

OG0061430± 673(673 to )

OG0036530± 99999(99999 to )

OG0037.25± 2.63(2.63 to )

OG0047.78± 2.37(2.37 to )

OG00510.3± 1.72(1.72 to )

OG00611.9± 3.53(3.53 to )

OG00315.2± 99999(99999 to )

OG00316.6± 4.42(4.42 to )

OG00445.3± 12.9(12.9 to )

OG00588.0± 26.4(26.4 to )

OG00696.9± 50.8(50.8 to )

OG003306± 99999(99999 to )

OG0032.13± 0.609(0.609 to )

OG0041.57± 0.519(0.519 to )

OG0051.62± 0.446(0.446 to )

OG0063.21± 1.31(1.31 to )

OG0031.75± 99999(99999 to )

OG00322.4± 10.8(10.8 to )

OG00418.5± 11.4(11.4 to )

OG00523.5± 5.12(5.12 to )

OG00650.9± 13.5(13.5 to )

OG00340.3± 99999(99999 to )

OG000	AMG 211 200 µg/Day for 7/14 Days	In cycle 1 participants received 200 µg/day AMG 211 administered as a cIV infusion at a constant flow rate for 7 days followed by a 3-week treatment-free interval. In cycle 2 and thereafter, participants received 200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
OG001	AMG 211 200 µg/Day for 14 Days	Participants received 200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
OG002	AMG 211 400 µg/Day for 14 Days	Participants received 400 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
OG003	AMG 211 800 µg/Day for 14 Days	Participants received 800 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
OG004	AMG 211 1600 µg/Day for 14 Days	Participants received 1600 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
OG005	AMG 211 1600 µg/Day for 28 Days	Participants received 1600 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval.
OG006	AMG 211 3200 µg/Day for 14 Days	Participants received 3200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
OG007	AMG 211 3200 µg/Day for 28 Days	Participants received 3200 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval.
OG008	AMG 211 6400 µg/Day for 14 Days	Participants received 6400 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
OG009	AMG 211 6400 µg/Day for 28 Days	Participants received 6400 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval.
OG010	AMG 211 12,800 µg/Day for 28 Days	Participants received 12,800 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval.