Clinical Trials /

Safety Study of MGA271 in Refractory Cancer

NCT01391143

Description:

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.

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Head and Neck Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Prostate Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Safety Study of MGA271 in Refractory Cancer

Title

  • Brief Title: Safety Study of MGA271 in Refractory Cancer
  • Official Title: A Phase 1 Dose Escalation Study of MGA271 in Refractory Cancer
  • Clinical Trial IDs

    NCT ID: NCT01391143

    ORG ID: CP-MGA271-01

    Trial Conditions

    Prostate Cancer

    Melanoma

    Renal Cell Carcinoma

    Triple-negative Breast Cancer

    Head and Neck Cancer

    Bladder Cancer

    Non-small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms

    Trial 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.

    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).

    Trial Arms

    Name Type Description Interventions
    MGA271 Experimental Fc-optimized, humanized monoclonal antibody

    Eligibility 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Safety

    Secondary Outcome Measures

    Maximum tolerated dose

    Trial Keywords

    Prostate cancer

    Melanoma

    Renal cell carcinoma

    Triple-negative breast cancer

    Head and neck cancer

    Bladder cancer

    Non-small cell lung cancer

    Squamous cell carcinoma