Clinical Trials /

Safety Study of MGAH22 in HER2-positive Carcinomas

NCT01148849

Description:

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.

Related Conditions:
  • Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Safety Study of MGAH22 in <span class="go-doc-concept go-doc-biomarker">HER2</span>-positive Carcinomas

Title

  • Brief Title: Safety Study of MGAH22 in HER2-positive Carcinomas
  • 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
  • Clinical Trial IDs

    NCT ID: NCT01148849

    NCT Alias ID: NCT01195935

    ORG ID: CP-MGAH22-01

    NCI ID: 02598-10

    Trial Conditions

    Breast Cancer

    Gastric Cancer

    Trial Interventions

    Drug Synonyms Arms

    Trial 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.

    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.

    Trial Arms

    Name Type Description Interventions
    MGAH22 Experimental Anti-HER2 monoclonal antibody

    Eligibility 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Occurrence of Adverse Events and Serious Adverse Events

    Secondary Outcome Measures

    Maximum tolerated dose

    Trial Keywords

    HER2 positive

    breast cancer

    gastric cancer