Safety Study of MGAH22 in HER2-positive Carcinomas

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by MacroGenics
Sponsor:
Collaborators:
Green Cross Corporation
Information provided by (Responsible Party):
MacroGenics
ClinicalTrials.gov Identifier:
NCT01148849
First received: June 17, 2010
Last updated: May 2, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to determine if MGAH22 is safe when given by intravenous (IV) infusion to patients with HER2-positive cancer. The study will also evaluate how long MGAH22 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 has an effect on tumors.


Condition Intervention Phase
Breast Cancer
Gastric Cancer
Bladder Cancer
Ovarian Cancer
Non-small Cell Lung Cancer
Biological: MGAH22
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 MGAH22 in Patients With Refractory HER2 Positive Breast Cancer and Patients With Other HER2 Positive Carcinomas for Whom No Standard Therapy Is Available

Resource links provided by NLM:


Further study details as provided by MacroGenics:

Primary Outcome Measures:
  • Occurrence of Adverse Events and Serious Adverse Events [ Time Frame: Study Day 50 or 28 days after last infusion ] [ Designated as safety issue: Yes ]
    Note that serious adverse events that are considered study drug related can be reported at any time after Study Day 50 or 28 days after the last infusion.


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

Estimated Enrollment: 36
Study Start Date: July 2010
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MGAH22
Anti-HER2 monoclonal antibody
Biological: MGAH22
MGAH22 will be administered by IV infusion once per week for 4 weeks in the following dose escalation cohorts: 0.1, 0.3, 1.0, 3.0, and 6.0 mg/kg; and once every 3 weeks in the following dose escalation cohorts: 10.0, 15.0, and 18.0 mg/kg.

Detailed Description:

An open-label, multi-dose, single-arm, multi-center, Phase 1, dose-escalation study will be conducted to define the toxicity profile, MTD, PK, immunogenicity, and potential antitumor activity of MGAH22 in patients with refractory HER2 positive breast cancer and patients with other carcinomas that overexpress HER2 for whom no standard therapy is available. After an MTD has been defined, an additional cohort of patients will be treated at the MTD to obtain further information regarding the safety of the chosen dose, to definitively describe PK, and to evaluate potential anti-tumor activity of MGAH22.

Patients will be monitored for a minimum of four weeks after administration of the final dose of MGAH22. The National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE), v.4.0, will be used for grading AEs except as noted within the protocol. Study assessments will include AE monitoring, ECG monitoring, PK analysis of serum MGAH22, determination of the serum concentration of soluble MGAH22 and tumor markers, and an assessment of potential anti-MGAH22 antibody [human anti-chimeric antibody (HACA)] response.

Tumor response assessments using Study Day 43 CT scans will be performed approximately six weeks after the first MGAH22 dose for each patient. Patients with evidence of disease regression (partial or complete response by RECIST criteria in patients with measurable disease or stable measurable or evaluable disease with > 25% decline in relevant tumor marker) will be allowed to continue therapy at the same dose, or at a reduced dose if warranted by DLT or significant AE in Cycle 1. Subsequent cycles which will begin on Study Day 50 will consist of MGAH22 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 that overexpresses HER2 by immunohistochemistry (2+ or 3+ positivity by HercepTest or equivalent).
  • Progressive disease during or after last treatment regimen.
  • Appropriate treatment history for histological entity.
  • ECOG Performance Status <= 1.
  • Life expectancy >= 3 month.
  • Measurable disease or evaluable disease with relevant tumor marker elevation.
  • Acceptable laboratory parameters and adequate organ reserve.
  • Baseline LVEF >50%

Exclusion Criteria:

  • Lifetime anthracycline exposure > 350 mg/m2 of doxorubicin or equivalent
  • Major surgery within four weeks before enrollment.
  • Known hypersensitivity to murine or recombinant proteins, polysorbate 80, or any excipient contained in the drug formulation.
  • 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.
  • History of chronic or recurrent infections that require continual use of antiviral, antifungal, or antibacterial agents.
  • History of deep vein thrombosis, pulmonary embolism, myocardial infarction, or stroke within three months of enrollment.
  • Known history of central nervous system (CNS) metastatic disease with evidence of residual or recurrent disease upon entry.
  • New York Heart Association class III or IV heart disease.
  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: NCT01148849

Contacts
Contact: Jan E Baughman, MPH 650 624 2600 baughmanj@macrogenics.com

Locations
United States, Maryland
National Cancer Institute Terminated
Bethesda, Maryland, United States, 20892
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Nurse referral line    615-339-4214      
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Yun Jeong Chae    (82)2-2072-1742 ext 107    yjchae0825@gmail.com   
Sponsors and Collaborators
MacroGenics
Green Cross Corporation
Investigators
Study Director: Stanford J. Stewart, MD MacroGenics
  More Information

No publications provided

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT01148849     History of Changes
Other Study ID Numbers: CP-MGAH22-01, 02598-10
Study First Received: June 17, 2010
Last Updated: May 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by MacroGenics:
HER2 positive
breast cancer
gastric cancer
bladder cancer
ovarian cancer
non-small cell lung cancer

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Breast Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Stomach Neoplasms
Ovarian Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Endocrine Gland Neoplasms
Ovarian Diseases

ClinicalTrials.gov processed this record on August 28, 2014