Phase 1 Study of Anti-Macrophage Migration Inhibitory Factor (Anti-MIF) Antibody in Solid Tumors

Tracking Information
First Submitted Date ICMJE	January 9, 2013
First Posted Date ICMJE	January 10, 2013
Last Update Posted Date	October 23, 2017
Study Start Date ICMJE	June 2012
Actual Primary Completion Date	July 2016 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 9, 2013)	Number of participants experiencing serious adverse events (SAEs) and/or adverse events (AEs) regardless of causality [ Time Frame: 14 months ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01765790 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 11, 2014)	Plasma pharmacokinetic parameters [ Time Frame: 28 days ]Maximum concentration (Cmax), minimum concentration (Cmin), area under the concentration vs time curve (AUC), half-life [t½], clearance (CL), mean residence time (MRT) and volume of distribution at steady state (VDss); Tumor response [ Time Frame: 14 months ]; Levels of free active MIF and free total MIF in plasma and tumor tissue (where applicable) [ Time Frame: 14 months ]; Change in levels of tumor-associated biomarkers, if applicable based on cancer type, following treatment with anti-MIF antibody [ Time Frame: 14 months ]; Number of serious adverse events (SAEs) and/or adverse events (AEs), regardless of causality [ Time Frame: 14 Months ]; Number of participants experiencing related serious adverse events (SAEs) and/or adverse events (AEs) [ Time Frame: 14 months ]; Number of related serious adverse events (SAEs) and/or adverse events (AEs) [ Time Frame: 14 months ]; Number of dose limiting toxicities (DLTs) [ Time Frame: 14 months ]; Number of participants experiencing dose limiting toxicity (DLT) [ Time Frame: 14 months ]; Number of participants who develop binding and/or neutralizing anti-anti-macrophage migration inhibitory factor (anti-MIF) antibodies following treatment with anti-MIF [ Time Frame: 14 months ]; Anti-MIF antibody in tumor tissues, bound and/or unbound to active MIF (where applicable) [ Time Frame: 14 Months ]; Levels of other potential biomarkers in tumor tissue (where applicable) [ Time Frame: 14 Months ]
Original Secondary Outcome Measures ICMJE; (submitted: January 9, 2013)	Plasma pharmacokinetic parameters [ Time Frame: 28 days ]Maximum concentration (Cmax), minimum concentration (Cmin), area under the concentration vs time curve (AUC), half-life [t½], clearance (CL), mean residence time (MRT) and volume of distribution at steady state (VDss); Tumor response [ Time Frame: 14 months ]; Change in levels of free active MIF and free total MIF levels following treatment with anti-MIF antibody [ Time Frame: 14 months ]; Change in levels of tumor-associated biomarkers following treatment with anti-MIF antibody [ Time Frame: 14 months ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Phase 1 Study of Anti-Macrophage Migration Inhibitory Factor (Anti-MIF) Antibody in Solid Tumors
Official Title ICMJE	A Phase 1 Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Anti-MIF Antibody in Subjects With Malignant Solid Tumors
Brief Summary	The purpose of the study is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of anti-MIF antibody in subjects with malignant solid tumors (Arm 1) and in subjects with metastatic adenocarcinoma of the colon or rectum (Arm 2).
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Metastatic Adenocarcinoma of the Colon or Rectum; Malignant Solid Tumors
Intervention ICMJE	Biological: Anti-Macrophage Migration Inhibitory Factor (Anti-MIF) Antibody Dosing every 2 weeks Intravenous injection; Biological: Anti-Macrophage Migration Inhibitory Factor (Anti-MIF) Antibody Dosing weekly Intravenous injection
Study Arms	Experimental: Malignant Solid Tumor (Arm 1) Dose Escalation Phase- Standard dose escalation of anti-MIF antibody in 5 dose groups of 3-6 participants each according to 3+3 design: 1. Dose escalation will be performed after safety data review, following completion of dosing of each cohort. -> 2. Safety data review. If dose escalation permissible -> 3. Next dose group -> 4. Safety data review, etc. Dose Expansion Phase- Enrollment of up to 6 participants to receive anti-MIF antibody (at the maximum tolerated dose or lower) in order to gain further experience with the investigational product at a specific dose level(s). Intervention: Biological: Anti-Macrophage Migration Inhibitory Factor (Anti-MIF) Antibody; Experimental: Metastatic Adenocarcinoma of the Colon or Rectum (Arm 2) Dose Escalation Phase- Standard dose escalation of anti-MIF antibody in 3 dose groups of 3-6 participants each according to 3+3 design: 1. Dose escalation will be performed after safety data review, following completion of dosing of each cohort. -> 2. Safety data review. If dose escalation permissible -> 3. Next dose group -> 4. Safety data review, etc. Dose Expansion Phase- Enrollment of up to 6 participants to receive anti-MIF antibody (at the maximum tolerated dose or lower) in order to gain further experience with the investigational product at a specific dose level(s). Intervention: Biological: Anti-Macrophage Migration Inhibitory Factor (Anti-MIF) Antibody
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: November 16, 2015)	68
Original Estimated Enrollment ICMJE; (submitted: January 9, 2013)	32
Actual Study Completion Date	July 2016
Actual Primary Completion Date	July 2016 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Main Inclusion Criteria: Males and females 18 years of age and older at the time of screening; Anticipated life expectancy > 3 months at the time of screening; Arm 1 only: Histologically confirmed malignant solid tumor which is refractory to or has failed standard treatments, or participant is not considered medically suitable to receive standard of care treatment or refuses standard of care treatment; Arm 2 only: Histologically or cytologically confirmed diagnosis of metastatic adenocarcinoma of the colon or rectum which is refractory to or has failed standard treatments, or participant is not considered medically suitable to receive standard of care treatment or refuses standard of care treatment; Measurable or evaluable disease (as defined in the study protocol); Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1; Adequate hematological function (as defined in the study protocol); Adequate renal function (as defined in the study protocol); Adequate liver function (as defined in the study protocol); Adequate venous access; Arm 2 only: At least 1 tumor that is amenable to biopsy, as determined by the investigator, and participant must be willing to undergo a biopsy prior to and at least once following anti-macrophage migration inhibitory factor (anti-MIF) antibody treatment; For women of childbearing potential, the participant must have a negative pregnancy test at screening and must agree to employ 2 forms of adequate contraceptive measures; For males, participants must agree to use adequate contraceptive measures including at least 1 barrier method, and abstain from sperm donation throughout the course of the study and for at least 90 days after the last administration of investigational product.; Participant is willing and able to comply with the requirements of the protocol Main Exclusion Criteria: Known brain tumors or Central nervous system (CNS) metastases; Myocardial infarction within 6 months of anti-MIF antibody administration, congestive heart failure (New York Heart Association Class III or Class IV), unstable angina, unstable cardiac arrhythmia requiring medication, or risk factors for polymorphic ventricular tachycardia; Uncontrolled hypertension; Left ventricular ejection fraction (LVEF) <40%, as determined by screening echocardiogram (echocardiogram results obtained within 90 days prior to screening are acceptable); QT/QTc interval >450 msec, as determined by screening electrocardiogram (ECG); Antitumor therapy (chemotherapy, radiotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, or hormonal therapy) within 4 weeks prior to administration of the investigational product (IP) (6 weeks for nitrosoureas and mitomycin C). Any previous treatment-related toxicities must have recovered to Grade ≤ 1 (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03). Prior and concurrent use of hormone deprivation therapies for hormone-refractory prostate cancer or breast cancer are permitted.; Major surgery within 4 weeks prior to IP administration; Active joint inflammation or history of inflammatory arthritis or other immune disorder involving the joints; Active infection requiring IV antibiotics within 2 weeks prior to screening; Known history of hepatitis B virus (HBV), hepatitis C virus (HCV), or active tuberculosis. Known history of human immunodeficiency virus (HIV) type 1/2 or other immunodeficiency disease.; Participant has received a live vaccine within 4 weeks prior to screening; Known hypersensitivity to any component of recombinant protein production by Chinese Hamster Ovary (CHO) cells; Participant has been exposed to an investigational product (IP) or investigational device in another clinical study within 4 weeks prior to IP administration, or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study; Participant is nursing or intends to begin nursing during the course of the study; Any disorder or disease, or clinically significant abnormality on laboratory or other clinical test(s), that in medical judgment may impede the participant's participation in the study, pose increased risk to the participant, or confound the results of the study; Participant is a family member or employee of the investigator
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Germany, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01765790
Other Study ID Numbers ICMJE	391101; 2013-002870-31 ( EudraCT Number )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Shire ( Baxalta now part of Shire )
Study Sponsor ICMJE	Baxalta now part of Shire
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Jenny Chen, MD Baxalta now part of Shire
PRS Account	Shire
Verification Date	September 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP