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Safety Study of MGA271 in Refractory Cancer

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ClinicalTrials.gov Identifier: NCT01391143
Recruitment Status : Active, not recruiting
First Posted : July 11, 2011
Last Update Posted : March 23, 2018
Sponsor:
Information provided by (Responsible Party):
MacroGenics

Brief Summary:
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 or disease Intervention/treatment 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

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).


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 179 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Study of MGA271 in Refractory Cancer
Study Start Date : July 2011
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2018


Arm Intervention/treatment
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.




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


Secondary Outcome Measures :
  1. Maximum tolerated dose [ Time Frame: Study Day 50 or 28 days after last infusion ]

Other Outcome Measures:
  1. Tumor response [ Time Frame: Every 8 weeks ]
    Efficacy will be assessed every 8 weeks in the Expansion Segment according to immune-related response criteria



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01391143


Locations
United States, California
UCLA Hematology-Oncology Clinic
Los Angeles, California, United States, 90095
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
United States, Kentucky
Norton Cancer Institute
Louisville, Kentucky, United States, 40202
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Neely Center for Clinical Cancer Research, Tufts Medical Center
Boston, Massachusetts, United States, 02111
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, North Carolina
Carolina Biooncology Institute
Huntersville, North Carolina, United States, 28078
United States, Pennsylvania
Hospital of the University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
MacroGenics
Investigators
Study Director: James Vasselli, MD MacroGenics

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT01391143     History of Changes
Other Study ID Numbers: CP-MGA271-01
First Posted: July 11, 2011    Key Record Dates
Last Update Posted: March 23, 2018
Last Verified: March 2018

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