Panitumumab and Irinotecan for Malignant Gliomas
Condition: Malignant Glioma of Brain
MeSH terms: Glioma
Intervention: Irinotecan; Panitumumab
Intervention description: Irinotecan: for those patients on an enzyme-inducing anti-epileptic drug (EIAED), irinotecan will be dosed at 340 mg/m2 every other week. For those not on an EIAED, irinotecan will be dosed at 125 mg/m2. Treatment on both drugs will continue until tumor progression or unacceptable toxicity.; Panitumumab, 6 mg/kg, as an intravenous infusion every other week. Treatment on both drugs will continue until tumor progression or unacceptable toxicity.
Intervention MeSH terms: Irinotecan; Panitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Panitumumab; Vectibix; Irinotecan; CPT-11; Camptosar; Malignant glioma; Glioblastoma multiforme; Gliosarcoma; Duke; Vredenburgh; Pro00015447

Summary:

      This is a phase II study of the combination of panitumumab with irinotecan in malignant
      glioma patients. The primary objective of the study is to determine the activity of the
      combination of panitumumab with irinotecan as measured by 6-month progression-free survival.
      Secondary objectives include the following- to determine the safety of panitumumab in
      combination with irinotecan in patients with malignant glioma; to determine the effect of
      panitumumab in combination with irinotecan on corticosteroid dose for each patient; to
      explore any relationship between epidermal growth factor receptor (EGF-R) mutational analysis
      and efficacy or toxicity; and, to determine the response rate and overall survival of
      recurrent glioblastoma (GBM) patients treated with panitumumab in combination with
      irinotecan.

      The patients will have histologically documented grade 4 malignant gliomas (glioblastoma
      multiforme or gliosarcoma) that have failed at least one prior chemotherapy regimen and all
      patients will have received radiation therapy. This study will investigate second or greater
      line of therapy for recurrent grade 4 malignant glioma. The patient population will include
      32 patients.

      The patients will undergo a baseline magnetic resonance imaging (MRI) as well as a MRI after
      every six-week cycle to determine response and progression. After 16 patients with recurrent
      GBM are treated, an interim analysis will be conducted. The most common side effects
      associated with panitumumab have been dermatological (skin) problems such as erythema
      (redness of the skin), acneiform rash (skin eruptions of the face), skin exfoliation,
      pruritus (itching), skin fissures (skin tears), xerosis (dryness of the eye, skin, or mouth),
      and rash. The most common side effects associated with irinotecan have been decreased blood
      counts of platelets (increased risk of bleeding), white blood cells (increased risk of
      infection), red blood cells (anemia); diarrhea, constipation, nausea, vomiting, tiredness,
      fever, mouth sores, dehydration (excessive loss of body fluids), rash, itching, changes in
      skin color, swelling, numbness, tingling, dizziness, confusion, low blood pressure, sweating,
      hot flashes, hair loss, inflammation of the liver, flu-like symptoms, decreased urine output,
      shortness of breath, and pneumonia (inflammatory disease of the lungs).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed diagnosis of primary malignant glioma
             (glioblastoma multiforme or gliosarcoma). Patients with recurrent disease whose
             diagnostic pathology confirmed grade IV malignant glioma (glioblastoma multiforme or
             gliosarcoma) will not need re-biopsy.

          -  Age ≥ 18 years.

          -  Evidence of measurable recurrent or residual primary central nervous system (CNS)
             neoplasm on contrast-enhanced MRI

          -  An interval of at least 4 weeks between prior surgical resection, or major surgery
             requiring general anesthesia or 1 week between prior biopsy or minor surgical
             procedures and study enrollment. The subjects must have recovered from all surgery
             related toxicities.

          -  An interval of at least 12 weeks between prior radiotherapy or 4 weeks from prior
             monthly chemotherapy, or 7 days from daily chemotherapy.

          -  The lab values following the prior chemotherapy must return to the baseline prior to
             study enrollment.

          -  Karnofsky ≥ 70%.

          -  Hematocrit ≥ 29%, absolute neutrophil count (ANC) ≥ 1,500 cells/μl, platelets ≥
             125,000 cells/μl.

          -  Serum creatinine ≤ 1.5 mg/dl, serum magnesium, potassium, calcium, chloride, and
             sodium ≥ the lower limit of normal, serum glutamic-oxaloacetic transaminase (SGOT) and
             bilirubin ≤ 1.5 times upper limit of normal.

          -  Signed informed consent approved by the Institutional Review Board prior to patient
             entry.

          -  If sexually active, patients will take contraceptive measures for the duration of the
             treatments, and for 6 months afterwards.

        Exclusion Criteria:

          -  Pregnancy or breast feeding

          -  Co-medication that may interfere with study results; e.g. immuno¬suppressive agents
             other than corticosteroids.

          -  Active infection requiring intravenous antibiotics.

          -  uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) homozygous for the 7/7
             genotype.

          -  Pre-existing diarrhea greater than Grade 1.

        Panitumumab-Specific Concerns:

        [Subjects meeting any of the following criteria are ineligible for study entry]

          -  Prior anti-epidermal growth factor receptor (EGFr) antibody therapy or treatment with
             small molecule EGFr inhibitors

          -  Clinically significant cardiovascular disease (including myocardial infarction,
             unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac
             arrhythmia) ≤ 1 year before enrollment.

          -  History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or
             evidence of interstitial lung disease on baseline chest CT scan.

          -  History of any medical or psychiatric condition or laboratory abnormality that in the
             opinion of the investigator may increase the risk associated with the study
             participation or investigational product(s) administration or may interfere with the
             interpretation of the results.

          -  Subject unwilling or unable to comply with study requirements

          -  Subject pregnant or breast feeding, or planning to become pregnant within 6 months
             after the end of treatment.

          -  Subject (male or female) is not willing to use highly effective methods of
             contraception (per institutional standard) during treatment and for 6 months (male or
             female) after the end of treatment.

          -  Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus,
             acute or chronic active hepatitis B infection(testing is not required in the absence
             of clinical suspicion)

          -  Patients with a history of deep venous thrombosis, pulmonary embolism or on
             therapeutic anti-coagulation.

          -  Known allergy or hypersensitivity to any component of the study treatment(s)

          -  Active infection requiring systemic intravenous treatment of any uncontrolled
             infections ≤14 days prior to enrollment/randomization.