Safety Study of MGA271 in Refractory Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by MacroGenics
Sponsor:
Information provided by (Responsible Party):
MacroGenics
ClinicalTrials.gov Identifier:
NCT01391143
First received: July 7, 2011
Last updated: October 15, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to evaluate the safety of MGA271 when given by intravenous (IV) infusion to patients with refractory cancer. The study will also evaluate how long MGA271 stays in the blood and how long it takes for it to leave the body, what is the highest dose that can safely be given, and whether it may have an effect on tumors.


Condition Intervention Phase
Prostate Cancer
Melanoma
Biological: MGA271
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Study of MGA271 in Refractory Cancer

Resource links provided by NLM:


Further study details as provided by MacroGenics:

Primary Outcome Measures:
  • Safety [ Time Frame: Study Day 50 or 28 days after last infusion ] [ Designated as safety issue: Yes ]
    Adverse events, serious adverse events, ECG monitoring, adrenal function monitoring, monitoring for development of anti-drug antibodies


Secondary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: Study Day 50 or 28 days after last infusion ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 93
Study Start Date: July 2011
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MGA271
Fc-optimized, humanized monoclonal antibody
Biological: MGA271
Up to 9 dose escalation cohorts will be enrolled to determine the maximum tolerated dose of MGA271. Patients with evidence of clinical benefit will be allowed to continue therapy at the same dose once per week for 3 weeks out of every 4-week cycle until documented progression.

Detailed Description:

An open-label, multi-dose, single-arm, multi-center, Phase 1, dose-escalation study will be conducted to define the toxicity profile, maximum tolerated dose (MTD), pharmacokinetics (PK), immunogenicity, and potential antitumor activity of MGA271 in patients with refractory cancer that expresses B7-H3.

Patients will be monitored for a minimum of four weeks after administration of the final dose of MGA271. Study assessments will include adverse event (AE) monitoring, electrocardiogram (ECG) monitoring, PK analysis of serum MGA271, determination of the serum concentration of soluble MGA271 and tumor markers, and an assessment of potential anti-MGA271 antibody [human anti-human antibody (HAHA)] response.

Tumor response assessments using Study Day 43 CT scans or MRI will be performed approximately six weeks after the first MGA271 dose for each patient. Patients with evidence of clinical benefit (partial or complete response or stable disease by RECIST or RANO Response criteria) will be allowed to continue therapy at the same dose, or at a reduced dose if warranted by dose limiting toxicity (DLT) or significant AE in Cycle 1. Subsequent cycles which will begin on Study Day 50 will consist of MGA271 administration on Study Days 1, 8, and 15 of each 28-day cycle, with tumor evaluation every other cycle. Responding patients may receive continued antibody therapy until evidence of progression of disease is documented or the patient experiences DLT.

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed carcinoma, melanoma, or glioblastoma that overexpresses B7-H3.
  • Progressive disease during or after last treatment regimen.
  • Appropriate treatment history for histological entity.
  • ECOG Performance Status <= 1.
  • Life expectancy >= 3 months.
  • Measurable disease or evaluable disease with relevant tumor marker elevation.
  • Acceptable laboratory parameters and adequate organ reserve.

Exclusion Criteria:

  • Evidence of adrenal insufficiency by rapid Cosyntropin stimulation test (patients with glioblastoma who have or are receiving steroids in past 4 months will be exempted from this exclusion).
  • Major surgery or trauma within four weeks before enrollment.
  • Known hypersensitivity to murine or recombinant proteins, polysorbate 80, or any excipient contained in the drug formulation.
  • History of autoimmune disease associated with ipilimumab therapy.
  • Second primary malignancy that has not been in remission for greater than 3 years. Treated non-melanoma skin cancer, cervical carcinoma in situ on biopsy, or squamous intraepithelial lesion on PAP smear, localized prostate cancer (Gleason score < 6), or resected melanoma in situ are exceptions and do not require a 3 year remission.
  • Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within four weeks of enrollment. Patients requiring any oral antiviral, fungal, or bacterial therapy must have completed treatment within one week of enrollment.
  • Vaccination within 2 weeks of enrollment (except for annual flu vaccine).
  • History of chronic or recurrent infections that require continual use of antiviral, antifungal, or antibacterial agents.
  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: NCT01391143

Contacts
Contact: Jan E Baughman, MPH 650 624-2676 baughmanj@macrogenics.com

Locations
United States, Massachusetts
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
Contact: Keith T. Flaherty, M.D.    617-724-4800      
Principal Investigator: Keith Flaherty, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Andrew Wolanski, NP    617-632-6623      
Principal Investigator: Geoffrey Shapiro, MD, PhD         
United States, Pennsylvania
Hospital of the University of Pennsylvania/Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Maryann Redlinger, RN    215-662-7452    maryann.redlinger@uphs.upenn.edu   
Principal Investigator: Roger Cohen, M.D.         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Nurse Referral Line    615-339-4214      
Principal Investigator: Howard Burris, MD         
Sponsors and Collaborators
MacroGenics
Investigators
Study Director: Stanford J Stewart, MD MacroGenics
  More Information

No publications provided

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT01391143     History of Changes
Other Study ID Numbers: CP-MGA271-01
Study First Received: July 7, 2011
Last Updated: October 15, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by MacroGenics:
Prostate cancer
Melanoma

Additional relevant MeSH terms:
Melanoma
Prostatic Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on September 22, 2014