Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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: November 4, 2014
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
Renal Cell Carcinoma
Triple-negative Breast Cancer
Head and Neck Cancer
Bladder Cancer
Non-small Cell Lung Cancer
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 ]

Other Outcome Measures:
  • Tumor response [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
    Efficacy will be assessed every 8 weeks in the Expansion Segment according to immune-related response criteria


Estimated Enrollment: 151
Study Start Date: July 2011
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2016 (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.

Patients treated in the Expansion Segment at the maximum administered dose will receive weekly, uninterrupted infusions of MGA271 in 8 week cycles for up to 12 cycles.


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.

In the initial segments of the study, 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.

In the Expansion Segment of the study, patients will receive weekly, uninterrupted infusions with an initial response assessment at 8 weeks. Tumor evaluation will be carried out by both RECIST and immune-related response criteria (irRC).

  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 (prostate cancer, renal cell carcinoma, head and neck cancer, triple-negative breast cancer, bladder cancer, non-small cell lung cancer) or melanoma 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:

  • 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.
  • Grade 3 colitis, hepatitis, pneumonitis uveitis, myocarditis, myositis, CNS toxicity or autoimmune related neuromuscular toxicity such as myasthenia gravis associated with the administration of an immune checkpoint inhibitor
  • 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, California
UCLA Hematology-Oncology Clinic Recruiting
Los Angeles, California, United States, 90095
Contact: Christine Kivork    310-794-2464      
Principal Investigator: Bartosz Chmielowski, MD, PhD         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Allison Richards, MS    813-745-8352    allison.richards@moffitt.org   
Principal Investigator: Jeffrey Weber, M.D, PhD         
United States, Illinois
The University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Katie McKeough, MA    773-702-9136      
Contact: David Geary, MSN    (773) 834-1942      
Principal Investigator: Russell Szmulewitz, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Andrew Wolanski, NP    617-632-6623      
Principal Investigator: Geoffrey Shapiro, MD, PhD         
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         
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: James Vasselli, 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: November 4, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by MacroGenics:
Prostate cancer
Melanoma
Renal cell carcinoma
Triple-negative breast cancer
Head and neck cancer
Bladder cancer
Non-small cell lung cancer
Squamous cell carcinoma

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Head and Neck Neoplasms
Lung Neoplasms
Melanoma
Prostatic Neoplasms
Triple Negative Breast Neoplasms
Urinary Bladder Neoplasms
Adenocarcinoma
Breast Diseases
Bronchial Neoplasms
Carcinoma, Bronchogenic
Genital Diseases, Male
Genital Neoplasms, Male
Kidney Diseases
Kidney Neoplasms
Lung Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Prostatic Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on November 25, 2014