Safety Study of MGAH22 in HER2-positive Carcinomas
Breast Cancer - Gastric Cancer
Conditions: official terms
Breast Neoplasms - Stomach Neoplasms
Conditions: Keywords
HER2 positive, breast cancer, gastric cancer
Study Type
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: MGAH22
Type: Biological
Overall Status
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.
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 or stable disease by RECIST criteria) 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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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

- 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.
National Cancer Institute
Bethesda, Maryland, United States
Status: Terminated
Sarah Cannon Research Institute
Nashville, Tennessee, United States
Status: Recruiting
Contact: Nurse referral line - 615-339-4214
Seoul National University Hospital
Seoul, Korea, Republic of
Status: Recruiting
Contact: Yun Jeong Chae - (82)2-2072-1742 -
Start Date
July 2010
Completion Date
March 2016
Record processing date processed this data on July 28, 2015 page