GI AdenocarcinomaPhase 1NCT02291614
A Phase 1 Study of AMG 211 in Participants With Advanced Gastrointestinal Cancer
A Phase 1 study testing AMG 211 in people with GI Adenocarcinoma, run by Amgen at 5 sites in 2 countries.
Trial summary
The purpose of this Phase 1 study is to determine if AMG 211 given as a continous intravenous (IV) infusion is safe and tolerable in adult participants that have advanced gastrointestinal adenocarcinoma. The study will be conducted in multiple sites and test increasing doses of AMG 211. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GI Adenocarcinoma
- What is being tested?
- AMG 211
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 27 Nov 2014to 9 Jan 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent provided
- 18 years or older
- Advanced relapsed/refracted gastrointestinal adenocarcinoma
- At least 1 measurable tumor lesion
- Tumor tissue available or is willing to undergo biopsy of a tumor lesion before the start of treatment
- Adequate hematological, renal, and liver function
- Body weight ≥ 45 kg
- Other inclusion criteria may apply
Who cannot join
- Malignancy other than gastrointestinal (GI) adenocarcinoma requiring current therapy
- Evidence of uncontrolled systemic disease, active infection, Hepatitis B and/or C, human immunodeficiency virus (HIV), history of cardiac disease, history of significant central nervous system (CNS) disease, history of chronic autoimmune disease (with the exception of stable type 1 diabetes)
- Major surgery within 28 days of study day 1
- Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment in another investigational device or drug study. Other investigational procedures while participating in this study are excluded. Exception to this criterion is the participation in the optional Imaging Study and all procedures related to this study.
- Treatment with any chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for cancer within 14 days prior to study entry and not recovered from treatment
- Unresolved toxicities from prior anti-tumor therapy
Show all 9Show fewer
- Males or Females of reproductive potential, and unwilling to practice an acceptable method of effective birth control while on study through 30 days after receiving the last dose of study drug
- Females who are pregnant, planning to become pregnant, lactating/breastfeeding or who plan to breastfeed while on study through 30 days after receiving the last dose of study drug
- Other exclusion criteria may apply
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Germany3 sites
Research Site
Hamburg, 20246
Research Site
München, 81377
Research Site
Ulm, 89081
Netherlands2 sites
Research Site
Amsterdam, 1081 HV
Research Site
Groningen, 9713 GZ
About this study
Official title: A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 211 Administered as Continuous Intravenous Infusion in Subjects With Relapsed/Refractory Gastrointestinal Adenocarcinoma
The purpose of this Phase 1 study is to determine if AMG 211 given as a continous intravenous (IV) infusion is safe and tolerable in adult participants that have advanced gastrointestinal adenocarcinoma. The study will be conducted in multiple sites and test increasing doses of AMG 211. The safety of participants will be monitored by intensive assessment of vital signs, electrocardiograms, physical examinations, and laboratory tests. Efficacy will be assessed by the usual imaging procedures and their interpretation.
- Conditions
- GI Adenocarcinoma
- Being tested
- AMG 211
- Keywords
- Amgen, Phase 1, Clinical Trial, Oncology, GI adenocarcinoma, Immunotherapy
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 211Drug
Also called MEDI-565, MT111
continuous intravenous infusion (cIV) infusion in cycles from 7 to 28 days
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: AMG 211 |
| AMG 211 1600 µg/day for 28 Days | Experimental | Participants receive 1600 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval. Receives: Drug: AMG 211 |
| AMG 211 3200 µg/day for 14 Days | Experimental | Participants receive 3200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval. Receives: Drug: AMG 211 |
| AMG 211 3200 µg/day for 28 Days | Experimental | Participants receive 3200 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval. Receives: Drug: AMG 211 |
| AMG 211 6400 µg/day for 14 Days | Experimental | Participants receive 6400 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval. Receives: Drug: AMG 211 |
| AMG 211 6400 µg/day for 28 Days | Experimental | Participants receive 6400 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval. Receives: Drug: AMG 211 |
| AMG 211 12,800 µg/day for 28 Days | Experimental | Participants receive 12,800 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval. Receives: Drug: AMG 211 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: From first dose of study drug through end of treatment + 30 days (median time frame was 75.5 days).
Secondary outcomes (20)
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.
Measured: 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.
Maximum Observed Concentration (Cmax) of AMG 211 in Cycle 1 in Participants Who Received Dosing for 28 Days
Measured: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Area Under the Serum Concentration-Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days
Area under the serum concentration-time curve (AUC) from time 0 to the last quantifiable concentration was estimated using the linear trapezoidal method.
Measured: 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.
Area Under the Serum Concentration-Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration in Cycle 1 in Participants Who Received Dosing for 28 Days
Area under the serum concentration-time curve (AUC) from time 0 to the last quantifiable concentration was estimated using the linear trapezoidal method.
Measured: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf) in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days
Area under the serum concentration-time curve from time 0 to infinity was estimated using the linear trapezoidal method
Measured: 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.
Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf) in Cycle 1 in Participants Who Received Dosing for 28 Days
Area under the serum concentration-time curve from time 0 to infinity was estimated using the linear trapezoidal method
Measured: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Terminal Half-life (T1/2) of AMG-211 in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days
Terminal half-life (t1/2,z) calculated as t1/2,z = ln(2)/λz, where λz was the first-order terminal rate constant estimated via linear regression of the terminal log-linear phase.
Measured: 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.
Terminal Half-life of AMG-211 in Cycle 1 in Participants Who Received Dosing for 28 Days
Terminal half-life (t1/2,z) calculated as t1/2,z = ln(2)/λz, where λz was the first-order terminal rate constant estimated via linear regression of the terminal log-linear phase.
Measured: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Concentration of AMG 211 at Steady State (Css) in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days
Css was calculated as the average concentration between achievement of plateau and the end of infusion.
Measured: 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
Concentration of AMG 211 at Steady State (Css) in Cycle 1 in Participants Who Received Dosing for 28 Days
Css was calculated as the average concentration between achievement of plateau and the end of infusion.
Measured: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Serum Clearance of AMG 211 in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days
Serum clearance (CL) calculated as CL = (actual dose)/(serum concentrations at steady-state [Css] x 24).
Measured: 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.
Serum Clearance of AMG 211 in Cycle 1 in Participants Who Received Dosing for 28 Days
Serum clearance (CL) calculated as CL = (actual dose)/(serum concentrations at steady-state [Css] x 24).
Measured: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Volume of Distribution at Steady-state (Vss) in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days
Volume of distribution at steady-state calculated as (CL x t1/2,z)/0.693.
Measured: 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.
Volume of Distribution at Steady-state (Vss) in Cycle 1 in Participants Who Received Dosing for 28 Days
Volume of distribution at steady-state calculated as (CL x t1/2,z)/0.693.
Measured: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Number of Participants With Anti-AMG 211 Antibody Formation
Blood samples collected during the study were tested for anti-AMG 211 binding antibodies using an electrochemiluminescence-based bridging immunoassay. The number of participants with anti-AMG 211 antibody formation includes participants with a negative or no result at baseline and a positive antibody binding result postbaseline.
Measured: Predose and 24 hours after the end of infusion during each treatment cycle, until 4 weeks after the last dose. Median time frame was 75.5 days.
Number of Participants With an Overall Objective Response
Disease response was assessed by radiological imaging using standardized contrast-enhanced magnetic imaging (MRI) or computed tomography (CT), and evaluated according to the modified Immune-Related Response Criteria (irRC). Overall objective response was defined as a best response of immune-related Complete Response (irCR) or immune-related Partial Response (irPR), confirmed by a repeat, consecutive assessment no less than 4 weeks from the date of the first documented assessment. irCR: Complete disappearance of all lesions and no new lesions. irPR: Decrease in tumor burden ≥ 50% relative to baseline.
Measured: Disease response was assessed every second cycle (8-10 weeks) until 4 weeks after the last dose. The median time frame was 75.5 days.
Duration of Response
Duration of response was defined as the number of days between the date of the first tumor assessment indicating an objective response through to the subsequent date of progression as classified by modified irRC or death due to any cause. Analyzed in participants with an overall objective response.
Overall objective response was defined as a best response of immune-related Complete Response (irCR) or immune-related Partial Response (irPR), confirmed by a repeat, consecutive assessment no less than 4 weeks from the date of the first documented assessment. irCR: Complete disappearance of all lesions and no new lesions. irPR: Decrease in tumor burden ≥ 50% relative to baseline.
Measured: Disease response was assessed every second cycle (8-10 weeks) until 4 weeks after the last dose. The median time frame was 75.5 days.
Time to Response
Time to response was defined as the number of days from the first administration of AMG 211 to the first objective assessment of response as per modified irRC. Analyzed in participants with an overall objective response.
Overall objective response was defined as a best response of immune-related Complete Response (irCR) or immune-related Partial Response (irPR), confirmed by a repeat, consecutive assessment no less than 4 weeks from the date of the first documented assessment. irCR: Complete disappearance of all lesions and no new lesions. irPR: Decrease in tumor burden ≥ 50% relative to baseline.
Measured: Disease response was assessed every second cycle (8-10 weeks) until 4 weeks after the last dose. The median time frame was 75.5 days.
Time to Tumor Progression in Participants Treated at the Maximum Tolerated Dose (MTD)
Disease was assessed by radiological imaging using standardized contrast-enhanced MRI or CT, and evaluated according to the modified irRC. Immune-related progressed disease (irPD) was defined as an increase in tumor burden ≥ 25% relative to nadir (minimum recorded tumor burden), confirmed by a repeat, consecutive assessment no less than 4 weeks from the date of the first documented assessment.
Measured: From first dose of AMG 211 until tumor progression, assessed through the end of study (up to 4 weeks after the last dose). The median time frame was 75.5 days.
Progression Free Survival (PFS) at 6 Months in Participants Treated at the MTD
PFS was defined as the percentage of participants who were progression-free at 6 months.
Immune-related progressed disease (irPD) was defined as an increase in tumor burden ≥ 25% relative to nadir (minimum recorded tumor burden), confirmed by a repeat, consecutive assessment no less than 4 weeks from the date of the first documented assessment.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2014 (estimated)
- Study start27 Nov 2014
- Primary completion6 Nov 2017
- Study completion9 Jan 2018
Why it stopped: The study was terminated because of immunogenicity and business decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GI AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- MedImmune LLC
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02291614
- Sponsor's protocol ID
- 20130354
- Other IDs
- 2014-000201-12, 2014
- Status last verified
- Feb 2021
- First submitted
- 6 Nov 2014
- Last updated
- 16 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 211 Administered as Continuous Intravenous Infusion in Subjects With Relapsed/Refractory Gastrointestinal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT02291614
- Acronym / sponsor ID
- 20130354
- Conditions
- GI Adenocarcinoma
- Keywords
- Amgen, Phase 1, Clinical Trial, Oncology, GI adenocarcinoma, Immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated because of immunogenicity and business decision.
- Enrolment
- 45 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Collaborators
- MedImmune LLC
- Study start
- 27 Nov 2014 (actual)
- Primary completion
- 6 Nov 2017 (actual)
- Study completion
- 9 Jan 2018 (actual)
- First posted
- 14 Nov 2014 (estimated)
- Results
- Posted 24 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this Phase 1 study is to determine if AMG 211 given as a continous intravenous (IV) infusion is safe and tolerable in adult participants that have advanced gastrointestinal adenocarcinoma. The study will be conducted in multiple sites and test increasing doses of AMG 211. The safety of participants will be monitored by intensive assessment of vital signs, electrocardiograms, physical examinations, and laboratory tests. Efficacy will be assessed by the usual imaging procedures and their interpretation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| AMG 211 200 μg/day for 7/14 Days | Experimental | Drug: AMG 211In 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. |
| AMG 211 200 μg/day for 14 Days | Experimental | Drug: AMG 211Participants receive 200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval. |
| AMG 211 400 μg/day for 14 Days | Experimental | Drug: AMG 211Participants receive 400 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval. |
| AMG 211 800 μg/day for 14 Days | Experimental | Drug: AMG 211Participants receive 800 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval. |
| AMG 211 1600 μg/day for 14 Days | Experimental | Drug: AMG 211Participants receive 1600 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval. |
| AMG 211 1600 µg/day for 28 Days | Experimental | Drug: AMG 211Participants receive 1600 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval. |
| AMG 211 3200 µg/day for 14 Days | Experimental | Drug: AMG 211Participants receive 3200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval. |
| AMG 211 3200 µg/day for 28 Days | Experimental | Drug: AMG 211Participants receive 3200 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval. |
| AMG 211 6400 µg/day for 14 Days | Experimental | Drug: AMG 211Participants receive 6400 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval. |
| AMG 211 6400 µg/day for 28 Days | Experimental | Drug: AMG 211Participants receive 6400 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval. |
| AMG 211 12,800 µg/day for 28 Days | Experimental | Drug: AMG 211Participants receive 12,800 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Informed consent provided
- 18 years or older
- Advanced relapsed/refracted gastrointestinal adenocarcinoma
- At least 1 measurable tumor lesion
- Tumor tissue available or is willing to undergo biopsy of a tumor lesion before the start of treatment
Key exclusion criteria (9 listed)
- Malignancy other than gastrointestinal (GI) adenocarcinoma requiring current therapy
- Evidence of uncontrolled systemic disease, active infection, Hepatitis B and/or C, human immunodeficiency virus (HIV), history of cardiac disease, history of significant central nervous system (CNS) disease, history of chronic autoimmune disease (with the exception of stable type 1 diabetes)
- Major surgery within 28 days of study day 1
- Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment in another investigational device or drug study. Other investigational procedures while participating in this study are excluded. Exception to this criterion is the participation in the optional Imaging Study and all procedures related to this study.
- Treatment with any chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for cancer within 14 days prior to study entry and not recovered from treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 211Also: MEDI-565, MT111continuous intravenous infusion (cIV) infusion in cycles from 7 to 28 days | Drug | AMG 211 12,800 µg/day for 28 Days, AMG 211 1600 µg/day for 28 Days, 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 |
Primary outcome
Number of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: 28 days
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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug through end of treatment + 30 days (median time frame was 75.5 days).
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.
20 secondary outcomes
Maximum Observed Concentration (Cmax) of AMG 211 in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days
Time frame: 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.
Maximum Observed Concentration (Cmax) of AMG 211 in Cycle 1 in Participants Who Received Dosing for 28 Days
Time frame: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Area Under the Serum Concentration-Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days
Time frame: 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.
Area Under the Serum Concentration-Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration in Cycle 1 in Participants Who Received Dosing for 28 Days
Time frame: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf) in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days
Time frame: 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.
Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf) in Cycle 1 in Participants Who Received Dosing for 28 Days
Time frame: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Terminal Half-life (T1/2) of AMG-211 in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days
Time frame: 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.
Terminal Half-life of AMG-211 in Cycle 1 in Participants Who Received Dosing for 28 Days
Time frame: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Concentration of AMG 211 at Steady State (Css) in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days
Time frame: 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
Concentration of AMG 211 at Steady State (Css) in Cycle 1 in Participants Who Received Dosing for 28 Days
Time frame: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Serum Clearance of AMG 211 in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days
Time frame: 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.
Serum Clearance of AMG 211 in Cycle 1 in Participants Who Received Dosing for 28 Days
Time frame: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Volume of Distribution at Steady-state (Vss) in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days
Time frame: 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.
Volume of Distribution at Steady-state (Vss) in Cycle 1 in Participants Who Received Dosing for 28 Days
Time frame: Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.
Number of Participants With Anti-AMG 211 Antibody Formation
Time frame: Predose and 24 hours after the end of infusion during each treatment cycle, until 4 weeks after the last dose. Median time frame was 75.5 days.
Number of Participants With an Overall Objective Response
Time frame: Disease response was assessed every second cycle (8-10 weeks) until 4 weeks after the last dose. The median time frame was 75.5 days.
Duration of Response
Time frame: Disease response was assessed every second cycle (8-10 weeks) until 4 weeks after the last dose. The median time frame was 75.5 days.
Time to Response
Time frame: Disease response was assessed every second cycle (8-10 weeks) until 4 weeks after the last dose. The median time frame was 75.5 days.
Time to Tumor Progression in Participants Treated at the Maximum Tolerated Dose (MTD)
Time frame: From first dose of AMG 211 until tumor progression, assessed through the end of study (up to 4 weeks after the last dose). The median time frame was 75.5 days.
Progression Free Survival (PFS) at 6 Months in Participants Treated at the MTD
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMG 211 in people with GI Adenocarcinoma, run by Amgen at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-Limiting Toxicities (DLTs) (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2021.