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NCT01327612

Open Label Extension Study of Conatumumab and Ganitumab (AMG 479)

Completed Phase 2 Results posted Last updated 21 February 2021
What this trial tests

Phase 2 trial testing Modified FOLFOX6 in Advanced Solid Tumors in 12 participants. Completed in 5 February 2020.

Timeline
3 March 2011
Primary endpoint
5 February 2020
5 February 2020

Quick facts

Lead sponsorAmgen
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment12
Start date3 March 2011
Primary completion5 February 2020
Estimated completion5 February 2020
Sites12 locations across Spain, United States, Poland

Drugs / interventions tested

Conditions studied

Sponsor

Amgen — full company profile →

Who can join

18 and older, any sex, with Advanced Solid Tumors or Carcinoid. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Adverse Events Primary · From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

An adverse event is defined as any untoward medical occurrence in a clinical trial participant, including worsening of a pre-existing medical condition. The event does not necessarily have a causal relationship with study treatment.

GroupValue95% CI
20050118: Ganitumab 20 mg/kg2
20050171: Conatumumab 0.45 mg/kg1
20060295: Conatumumab 3 mg/kg1
20060340: Conatumumab 5 mg/kg1
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab2
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab3
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg2
Number of Participants With Serious Adverse Events Primary · From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria: * fatal, * life threatening (places the participant at immediate risk of death), * required in-patient hospitalization or prolongation of existing hospitalization, * resulted in persistent or significant disability/incapacity, * congenital anomaly/birth defect, and/or * other medically important serious event.

GroupValue95% CI
20050118: Ganitumab 20 mg/kg1
20050171: Conatumumab 0.45 mg/kg0
20060295: Conatumumab 3 mg/kg1
20060340: Conatumumab 5 mg/kg0
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab1
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab3
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg2
Maximum Change From Baseline in Blood Pressure Secondary · Baseline and day 1 of each treatment cycle (every 2, 3, or 4 weeks depending on dosing schedule) up to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

Maximum change from baseline is defined for each participant as the maximum change from baseline value observed across all visits.

Systolic blood pressure
GroupValue95% CI
20050118: Ganitumab 20 mg/kg5.5± 9.2
20050171: Conatumumab 0.45 mg/kg7.0
20060295: Conatumumab 3 mg/kg54.0
20060340: Conatumumab 5 mg/kg37.0
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab42.0± 0.0
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab26.0± 17.3
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg32.5± 31.8
Diastolic blood pressure
GroupValue95% CI
20050118: Ganitumab 20 mg/kg7.5± 9.2
20050171: Conatumumab 0.45 mg/kg1.0
20060295: Conatumumab 3 mg/kg10.0
20060340: Conatumumab 5 mg/kg13.0
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab27.5± 9.2
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab14.7± 6.4
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg23.5± 6.4
Minimum Change From Baseline in Blood Pressure Secondary · Baseline and day 1 of each treatment cycle (every 2, 3, or 4 weeks depending on dosing schedule) up to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

Minimum change from baseline is defined for each participant as the minimum change from baseline value observed across all visits.

Systolic blood pressure
GroupValue95% CI
20050118: Ganitumab 20 mg/kg-28.5± 17.7
20050171: Conatumumab 0.45 mg/kg-45.0
20060295: Conatumumab 3 mg/kg-20.0
20060340: Conatumumab 5 mg/kg-21.0
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab-22.5± 16.3
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab-29.0± 10.8
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg-12.0± 12.
Diastolic blood pressure
GroupValue95% CI
20050118: Ganitumab 20 mg/kg-19.5± 9.2
20050171: Conatumumab 0.45 mg/kg-27.0
20060295: Conatumumab 3 mg/kg-20.0
20060340: Conatumumab 5 mg/kg-25.0
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab-8.5± 7.8
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab-14.3± 5.5
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg-10.0± 4.2
Number of Participants With CTCAE Grade 3 or Higher Clinical Laboratory Toxicities Secondary · From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

Laboratory toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

GroupValue95% CI
20050118: Ganitumab 20 mg/kg0
20050171: Conatumumab 0.45 mg/kg0
20060295: Conatumumab 3 mg/kg1
20060340: Conatumumab 5 mg/kg0
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab2
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab2
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg1
Best Overall Response Secondary · Approximately every 6 months until end of treatment; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

Radiological assessments to evaluate disease extent (with change compared to nadir from the parent protocol) were performed at regular intervals, at a minimum once every 6 months or more frequently if clinically indicated (starting from their last scan on the parent protocol), per standard of care (SOC) at each facility. Tumor response was assessed by the Investigator as either complete response, partial response, stable disease, or progressive disease.

GroupValue95% CI
20050118: Ganitumab 20 mg/kg0
20050171: Conatumumab 0.45 mg/kg1
20060295: Conatumumab 3 mg/kg0
20060340: Conatumumab 5 mg/kg1
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab1
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab0
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg0
20050118: Ganitumab 20 mg/kg0
20050171: Conatumumab 0.45 mg/kg0
20060295: Conatumumab 3 mg/kg0
20060340: Conatumumab 5 mg/kg0
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab1
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab1
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg1
20050118: Ganitumab 20 mg/kg2
20050171: Conatumumab 0.45 mg/kg0
20060295: Conatumumab 3 mg/kg1
20060340: Conatumumab 5 mg/kg0
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab0
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab2
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg1
20050118: Ganitumab 20 mg/kg0
20050171: Conatumumab 0.45 mg/kg0
20060295: Conatumumab 3 mg/kg0
20060340: Conatumumab 5 mg/kg0
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab0
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab0
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg0
Number of Participants With Disease Progression or Death Due to Disease Progression Secondary · From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.
Disease progression
GroupValue95% CI
20050118: Ganitumab 20 mg/kg1
20050171: Conatumumab 0.45 mg/kg1
20060295: Conatumumab 3 mg/kg1
20060340: Conatumumab 5 mg/kg0
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab2
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab2
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg2
Death due to disease progression
GroupValue95% CI
20050118: Ganitumab 20 mg/kg0
20050171: Conatumumab 0.45 mg/kg0
20060295: Conatumumab 3 mg/kg0
20060340: Conatumumab 5 mg/kg0
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab1
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab0
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg0

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

20050118: Ganitumab 20 mg/kg
Serious: 1/2 (50%)
Deaths: 0/2
20050171: Conatumumab 0.45 mg/kg
Serious: 0/1 (0%)
Deaths: 0/1
20060295: Conatumumab 3 mg/kg
Serious: 1/1 (100%)
Deaths: 0/1
20060340: Conatumumab 5 mg/kg
Serious: 0/1 (0%)
Deaths: 0/1
20060464: Conatumumab 2 mg/kg + mFOLFOX6 + Bevacizumab
Serious: 1/2 (50%)
Deaths: 1/2
20060464: Conatumumab 10 mg/kg + mFOLFOX6 ± Bevacizumab
Serious: 3/3 (100%)
Deaths: 0/3
20070411: Conatumumab 15 mg/kg + Ganitumab 18 mg/kg
Serious: 2/2 (100%)
Deaths: 0/2

Serious adverse events (18 terms)

ReactionSystem20050118: Ganitumab 20 mg/kg20050171: Conatumumab 0.45…20060295: Conatumumab 3 mg…20060340: Conatumumab 5 mg…20060464: Conatumumab 2 mg…20060464: Conatumumab 10 m…20070411: Conatumumab 15 m…
Myocardial infarctionCardiac disorders
Abdominal painGastrointestinal disorders
Diverticular perforationGastrointestinal disorders
NauseaGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
VomitingGastrointestinal disorders
Abdominal wall abscessInfections and infestations
GastroenteritisInfections and infestations
Hepatitis CInfections and infestations
PneumoniaInfections and infestations
Hip fractureInjury, poisoning and procedural complications
HyponatraemiaMetabolism and nutrition disorders
Lumbar spinal stenosisMusculoskeletal and connective tissue disorders
Rectal cancer metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal failureRenal and urinary disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
Transurethral bladder resectionSurgical and medical procedures
Other adverse events (170 terms — click to expand)

ReactionSystem20050118: Ganitumab 20 mg/kg20050171: Conatumumab 0.45…20060295: Conatumumab 3 mg…20060340: Conatumumab 5 mg…20060464: Conatumumab 2 mg…20060464: Conatumumab 10 m…20070411: Conatumumab 15 m…
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
PyrexiaGeneral disorders
Amylase increasedInvestigations
Blood creatinine increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Tooth extractionSurgical and medical procedures
LeukopeniaBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
SplenomegalyBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Cardiac flutterCardiac disorders
CardiomegalyCardiac disorders
TachycardiaCardiac disorders
Periorbital oedemaEye disorders
Abdominal pain lowerGastrointestinal disorders
Dry mouthGastrointestinal disorders
DysphagiaGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
HaematocheziaGastrointestinal disorders
Lip painGastrointestinal disorders
Lip swellingGastrointestinal disorders
Loose toothGastrointestinal disorders
NauseaGastrointestinal disorders
Oral painGastrointestinal disorders
StomatitisGastrointestinal disorders
Tooth lossGastrointestinal disorders
ToothacheGastrointestinal disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
Catheter site painGeneral disorders
ChillsGeneral disorders
Gait disturbanceGeneral disorders
General physical health deteriorationGeneral disorders

Most-reported serious reactions: Myocardial infarction, Abdominal pain, Diverticular perforation, Nausea, Small intestinal obstruction, Vomiting, Abdominal wall abscess, Gastroenteritis.

Data from ClinicalTrials.gov NCT01327612 adverse events section.

Sponsor's own description

The purpose of this protocol is to allow continued treatment with conatumumab and/or ganitumab, with or without chemotherapy, to participants who completed a separate Amgen-sponsored conatumumab or ganitumab study without disease progression whose previous studies were closed.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Comprehensive review of targeted therapy for colorectal cancer.
    Xie YH, Chen YX, Fang JY. · · 2020 · cited 1162× · PMID 32296018 · DOI 10.1038/s41392-020-0116-z
  2. Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors.
    Ahola-Olli AV, Würtz P, Havulinna AS, Aalto K, et al · · 2017 · cited 528× · PMID 27989323 · DOI 10.1016/j.ajhg.2016.11.007
  3. TRAIL on trial: preclinical advances in cancer therapy.
    Stuckey DW, Shah K. · · 2013 · cited 216× · PMID 24076237 · DOI 10.1016/j.molmed.2013.08.007
  4. Molecular pathways and therapeutic targets in lung cancer.
    Shtivelman E, Hensing T, Simon GR, Dennis PA, et al · · 2014 · cited 150× · PMID 24722523 · DOI 10.18632/oncotarget.1891
  5. Principles of antibody-mediated TNF receptor activation.
    Wajant H. · · 2015 · cited 111× · PMID 26292758 · DOI 10.1038/cdd.2015.109
  6. TRAIL of Hope Meeting Resistance in Cancer.
    Deng D, Shah K. · · 2020 · cited 103× · PMID 32718904 · DOI 10.1016/j.trecan.2020.06.006
  7. Trial Watch: Immunostimulatory cytokines.
    Vacchelli E, Galluzzi L, Eggermont A, Galon J, et al · · 2012 · cited 70× · PMID 22754768 · DOI 10.4161/onci.20459
  8. Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab, teprotumumab and figitumumab) effects on cancer therapy.
    Qu X, Wu Z, Dong W, Zhang T, et al · · 2017 · cited 65× · PMID 28427155 · DOI 10.18632/oncotarget.15704

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01327612.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing