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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Baxter Healthcare Corporation
Sponsor:
Information provided by (Responsible Party):
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT01765790
First received: January 9, 2013
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

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).


Condition Intervention Phase
Malignant Solid Tumors
Metastatic Adenocarcinoma of the Colon or Rectum
Biological: Anti-Macrophage Migration Inhibitory Factor (Anti-MIF) Antibody
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Anti-MIF Antibody in Subjects With Malignant Solid Tumors

Resource links provided by NLM:


Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • Number of participants experiencing serious adverse events (SAEs) and/or adverse events (AEs) regardless of causality [ Time Frame: 14 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Plasma pharmacokinetic parameters [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Levels of free active MIF and free total MIF in plasma and tumor tissue (where applicable) [ Time Frame: 14 months ] [ Designated as safety issue: No ]
  • Change in levels of tumor-associated biomarkers, if applicable based on cancer type, following treatment with anti-MIF antibody [ Time Frame: 14 months ] [ Designated as safety issue: No ]
  • Number of serious adverse events (SAEs) and/or adverse events (AEs), regardless of causality [ Time Frame: 14 Months ] [ Designated as safety issue: Yes ]
  • Number of participants experiencing related serious adverse events (SAEs) and/or adverse events (AEs) [ Time Frame: 14 months ] [ Designated as safety issue: Yes ]
  • Number of related serious adverse events (SAEs) and/or adverse events (AEs) [ Time Frame: 14 months ] [ Designated as safety issue: Yes ]
  • Number of dose limiting toxicities (DLTs) [ Time Frame: 14 months ] [ Designated as safety issue: Yes ]
  • Number of participants experiencing dose limiting toxicity (DLT) [ Time Frame: 14 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Anti-MIF antibody in tumor tissues, bound and/or unbound to active MIF (where applicable) [ Time Frame: 14 Months ] [ Designated as safety issue: No ]
  • Levels of other potential biomarkers in tumor tissue (where applicable) [ Time Frame: 14 Months ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: June 2012
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

Biological: Anti-Macrophage Migration Inhibitory Factor (Anti-MIF) Antibody
  • Dosing every 2 weeks
  • Intravenous injection
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).

Biological: Anti-Macrophage Migration Inhibitory Factor (Anti-MIF) Antibody
  • Dosing weekly
  • Intravenous injection

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01765790

Contacts
Contact: Medical Information medinfo@baxter.com

Locations
United States, Arizona
Scottsdale Healthcare Recruiting
Scottsdale, Arizona, United States, 85258
United States, Florida
Florida Cancer Specialists / Sarah Cannon Research Institute Recruiting
Sarasota, Florida, United States, 34232
United States, Texas
Department of Investigator Cancer Therapeutics, University of Texas, MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Cancer Therapy and Research Center (CTRC), The University of Texas Health Science Center at San Antonio Recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Baxter Healthcare Corporation
Investigators
Study Director: Salim Yazji, MD Baxter Healthcare Corporation
  More Information

No publications provided

Responsible Party: Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT01765790     History of Changes
Other Study ID Numbers: 391101, 2013-002870-31
Study First Received: January 9, 2013
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Neoplasms
Colonic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014