Clinical Trials /

Phase 2 Study of Sym004 for Adult Patients With Recurrent Glioblastoma

NCT02540161

Description:

The purpose of this study is to assess the activity of Sym004, a recombinant antibody mixture that specifically binds to EGFR, in patients diagnosed with recurrent glioblastoma whose tumor is EGFR amplified. This is a phase 2 study that will accrue patients with WHO grade IV recurrent malignant glioma (glioblastoma or gliosarcoma) in two cohorts to assess the efficacy of Sym004.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Phase 2 Study of <span class="go-doc-concept go-doc-intervention">Sym004</span> for Adult Patients With Recurrent <span class="go-doc-concept go-doc-disease">Glioblastoma</span>

Title

  • Brief Title: Phase 2 Study of Sym004 for Adult Patients With Recurrent Glioblastoma
  • Official Title: Phase 2 Study of Sym004 for Adult Patients With Recurrent Glioblastoma
  • Clinical Trial IDs

    NCT ID: NCT02540161

    ORG ID: Pro00063483

    Trial Conditions

    Malignant Glioma

    Trial Interventions

    Drug Synonyms Arms
    Sym004 non-bevacizumab failures, bevacizumab failures

    Trial Purpose

    The purpose of this study is to assess the activity of Sym004, a recombinant antibody
    mixture that specifically binds to EGFR, in patients diagnosed with recurrent glioblastoma
    whose tumor is EGFR amplified. This is a phase 2 study that will accrue a total of 61
    patients with WHO grade IV recurrent malignant glioma (glioblastoma or gliosarcoma) in two
    cohorts to assess the efficacy of Sym004.

    Detailed Description

    The purpose of this study is to assess the activity of Sym004, a recombinant antibody
    mixture that specifically binds to EGFR, in patients diagnosed with recurrent glioblastoma
    whose tumor is EGFR amplified. The primary objective is to assess the activity of Sym004 in
    patients with recurrent glioblastoma that are either non bevacizumab failures (Cohort 1) or
    who have previously failed bevacizumab (Cohort 2), in terms of 6-month progression-free
    survival (PFS6). Secondary objectives include: 1. Determine the safety of Sym004 in
    recurrent Glioblastoma Multiforme (GBM) patients; 2. Estimate response rate (RR) within the
    two cohorts of recurrent GBM patients; 3. Describe overall survival (OS) within the two
    cohorts of recurrent GBM patients; 4. Describe overall median progress free survival (PFS)
    within the two cohorts of recurrent GBM patients.

    This is a phase 2 study that will accrue a total of 61 patients with WHO grade IV recurrent
    malignant glioma (glioblastoma or gliosarcoma) in two cohorts to assess the efficacy of
    Sym004. Both cohorts will accrue simultaneously, with 36 subjects in Cohort 1 and 25
    subjects in Cohort 2. Sym004 will be dosed at 18 mg/kg intravenously every 2 weeks. A
    treatment cycle will be 4 weeks.

    For the primary objective, progression free survival, based upon the Kaplan-Meier estimator,
    the percentage of patients who are alive and progression-free 6 months after initiation of
    Sym004 treatment will be estimated. For the secondary objectives, within each cohort, the
    percentage of patients who experience grade 3, 4, or 5 adverse events that are possibly,
    probably, and definitely related to protocol treatment will be estimated. Second, within
    each cohort, radiographic response rate will be estimated as the percentage of treated
    patients with a complete or partial response. An exact binomial confidence interval will be
    generated. Interim analyses that focus on the physiologic consequences of Sym004 treatment
    will be conducted after 19 total patients across both cohorts have been treated with Sym004.
    The most likely risks include skin reactions, electrolyte imbalance (especially low Mg, Ca,
    and K), diarrhea, generalized weakness, secondary skin and nail infection, nausea and
    vomiting, infusion-treated hypersensitivity reaction, and inflammation of mucous membranes.

    Trial Arms

    Name Type Description Interventions
    non-bevacizumab failures Experimental Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 at 18 mg/kg intravenously every two weeks. Sym004
    bevacizumab failures Experimental Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 at 18 mg/kg intravenously every two weeks. Sym004

    Eligibility Criteria

    Inclusion Criteria:

    1. Patients must have histologically confirmed diagnosis of World Health Organization
    (WHO) grade 4 malignant glioma and radiographic evidence of recurrence or disease
    progression (as defined by the Response Assessment in Neuro-Oncology (RANO) criteria
    as a greater than 25% increase in the largest bi-dimensional product of enhancement
    or a new enhancing lesion, or a significant increase in T2-weighted-Fluid-Attenuated
    Inversion Recovery (T2/FLAIR) abnormality without another co-morbid cause);

    2. Age 18 years;

    3. Karnofsky Performance Status 70%;

    4. No more than 3 prior progressions;

    5. Cohort 1 only: Non-bevacizumab failure, i.e. either no prior bevacizumab or
    bevacizumab stable/responder, which is defined as stable within 6 months of prior
    treatment with bevacizumab without experiencing a bevacizumab adverse event of
    special interest (AESI) while on a bevacizumab-containing regimen, such as:

    1. grade 3 hypertension not controlled by medication, hypertensive crisis, or
    hypertensive encephalopathy

    2. grade 3 proteinuria that does not resolve or nephrotic syndrome

    3. Any grade GI perforation

    4. grade 3 infusion-related reaction

    5. grade 3 woundhealing complications

    6. grade 3 hemorrhage or any grade central nervous system (CNS) hemorrhage or
    grade 2 hemoptysis

    7. Any grade arterial thromboembolic event (e.g. myocardial infarction or cerebral
    infarction) or grade 3 venous thromboembolic event

    8. Any grade posterior reversible encephalopathy syndrome (PRES)

    9. grade 3 congestive heart failure

    10. grade 2 non-gastrointestinal (GI) abscesses and fistulae;

    6. Cohort 2 only: Prior progression on a bevacizumab-containing regimen (defined as
    having progressed/grown through bevacizumab by RANO criteria within 2 months of prior
    bevacizumab treatment);

    7. Prior pathology consistent with Epidermal Growth Factor Receptor (EGFR)-amplification
    of tumor (i.e. greater than 15% of cells exhibiting > 5 copies of EGFR loci);

    8. Absolute Neutrophil Count (ANC) 1,000 cells/l, platelets 100,000 cells/l,
    hemoglobin 9 g/dL;

    9. Adequate renal function as indicated by the following:

    1. Serum creatinine < 1.25 times upper limit of normal or calculated creatinine
    clearance 50 ml/min;

    2. Urine dipstick for proteinuria < 2+ unless a 24-hour urine protein <1 g of
    protein is demonstrated;

    10. Adequate liver function as indicated by the following:

    1. Total bilirubin 1.6 mg/dL;

    2. Aspartate transaminase/alanine transaminase (AST/ALT) 2.5 x the upper limit of
    normal (ULN);

    11. Magnesium 0.9 mg/dL;

    12. For subjects on corticosteroids, they must be on a stable dose for 7 days prior to
    anticipated start of study drug;

    13. No evidence of > grade 1 active CNS hemorrhage on the baseline magnetic resonance
    imaging (MRI) or X-ray computed tomography (CT) scan;

    14. Signed informed consent approved by the Institutional Review Board prior to patient
    entry;

    15. If the patient is a sexually active female of child bearing potential whose partner
    is male, or if the patient is a sexually active male whose partner is a female of
    child bearing potential, the patient must agree to use appropriate contraceptive
    measures for the duration of the treatment of the tumor and for 6 months afterwards
    as stated in the informed consent. Female patients of child bearing potential must
    have a negative serum pregnancy test within 48 hours of starting study treatment;

    16. Fertile male subjects must agree to use a medically acceptable contraceptive method
    (allowed methods of birth control include vasectomy or condom with spermicide) during
    the trial and for a period of at least 6 months following the last administration of
    trial drugs.

    Exclusion Criteria:

    1. Pregnancy or breastfeeding;

    2. Prior treatment with EGFR-targeted therapy, including, but not limited to, the
    following examples: Gilotrif (afatinib),Tarceva (erlotinib), Erbitux (cetuximab),
    Iressa (gefitinib), Vectibix (panitumumab), Caprelsa (vandetanib), Tykerb
    (lapatinib), CDX110, D2C7-immunotoxin);

    3. Active infection requiring intravenous antibiotics within 7 days before enrollment;

    4. Prior, unrelated malignancy requiring current active treatment with the exception of
    cervical carcinoma in situ and adequately treated basal cell or squamous cell
    carcinoma of the skin;

    5. Less than 12 weeks from radiation therapy, unless progressive disease outside of the
    radiation field on 2 consecutive scans or histopathologic confirmation;

    6. Treated with immunotherapeutic agents, vaccines, or Mab therapy within 4 weeks before
    enrollment, unless the patient has recovered from the expected toxic effects of such
    therapy

    7. Treated with alkylating agents within 4 weeks (6 weeks for nitrosoureas) before
    enrollment or treated within 1 week before enrollment with daily or metronomic
    chemotherapy, unless the patient has recovered from the expected toxic effects of
    such therapy to their baseline or to grade 1;

    8. Prior treatment (non-alkylating agents) within 2 weeks before enrollment, unless the
    patient has recovered from the expected toxic effects of such therapy;

    9. Known hypersensitivity reactions to any of the components of Sym004;

    10. Known current drug abuse or alcohol abuse;

    11. Known Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C infection.
    Testing is not required as part of this study.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Six-month progression-free survival (PFS6)

    Secondary Outcome Measures

    Percentage of participants who experience grade 3, 4 or 5 adverse events

    Radiographic response

    Median progression-free survival (PFS)

    Median overall survival (OS)

    Trial Keywords