Ph. II Treatment of Adults w Primary Malignant Glioma w Irinotecan + Temozolomide
Ph. II Treatment of Adults w Primary Malignant Glioma w Irinotecan + Temozolomide
Objective:

 To determine activity of combo of Irinotecan + Temozolomide To further characterize any
 toxicity associated w combo of Irinotecan + Temozolomide
Objectives of study are to determine activity of combo of Irinotecan + Temozolomide & to
 further characterize any toxicity associated w combo of Irinotecan + Temozolomide.
 Temozolomide administered orally at 200mg/m2 in fasting state 1hr prior to CPT-11 infusion.
 Temozolomide administered on day 1 of treatment cycle & every 24hrs thereafter for 5 days w
 treatment cycles repeated every 6wks. Treatment cycles may be repeated up to maxi of 3 cycles
 until occurrence of either unacceptable toxicity/evidence of disease progression. At end of
 3rd cycle/if cycles are stopped early for toxicity or progression, subject will undergo
 radiation therapy. CPT-11 administered intravenously in fasting state over 90min. CPT-11 will
 begin 1hr after Temozolomide administration on day 1 of treatment cycle. CPT-11 administered
 on days 1, 8, 22, & 29 of 6wk treatment cycle. Treatment cycles may be repeated up to maxi of
 3 cycles until occurrence of either unacceptable toxicity/evidence of disease progression.
 Dose of CPT-11 will be based on whether pt is receiving CYP3A4-inducing antiepileptic drugs
 due to increased drug clearance produced by these agents. For pts receiving EIAEDs including
 phenytoin, fosphenytoin, oxcarbazepine, phenobarbital/ primidone, CPT-11 dose of 325mg/m2
 administered. For pts not receiving EIAEDs, CPT-11 dose of125 mg/m2 administered.

 Subjects have newly diagnosed histologically proven supratentorial glioblastoma multiforme.
 Toxicities associated w CPT-11 are anemia, decreased blood counts, diarrhea, constipation,
 nausea, vomiting, tiredness, fever, mouth sores, dehydration, rash, itching, changes in skin
 color, swelling, numbness, tingling, dizziness, confusion, low blood pressure, sweating, hot
 flashes, hair loss, inflammation of liver, flu-like symptoms, decreased urine output,
 shortness of breath,& pneumonia. Low white blood cell & platelet counts may be associated w
 risk of infection/bleeding, respectively. Irinotecan has also caused birth defects in
 animals. Most frequent toxicities in earlier studies have been low white blood cells &
 diarrhea, & death has been seen from these & other side effects. Temozolomide has been well
 tolerated by both adults & children w most common toxicity being mild myelosuppression.
 Other, less likely, potential toxicities include nausea & vomiting, constipation, headache,
 alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy,
 hepatotoxicity, anorexia, fatigue & hyperglycemia. Hypersensitivity reactions have not yet
 been noted w Temozolomide. As in case w many anti-cancer drugs, Temozolomide may be
 carcinogenic.
Inclusion Criteria:

 -  Pts have histologically proven supratentorial GBM

 -  Pts have newly diagnosed disease

 -  There must be measurable disease on contrast-enhanced magnetic resonance imaging
 performed <14 days before drug administration. Those who underwent resection must have
 MRI <72 hrs/ >14 days after surgery

 -  Prior Surgical Resection/Biopsy: Although surgical resection is not required, pts must
 be treated <42 days of surgery or biopsy

 -  Age >18 yrs

 -  Karnofsky Performance Status >70 percent

 -  Serum creatinine < 1.5 x ULN

 -  Absolute neutrophil count >1500 cells/microliter; platelet count >100,000
 cells/microliter

 -  Serum SGOT & total bilirubin <2.5 x ULN

 -  Signed informed consent, approved by IRB, will be obtained prior to initiating
 treatment

 -  Pts must agree to practice effective birth control measures while on study & for 2
 months after completing therapy

 Exclusion Criteria:

 -  Pregnant/breast feeding women / women/men w reproductive potential not practicing
 adequate contraception. This therapy may be associated w potential toxicity to
 fetus/child that exceeds minimum risks necessary to meet health needs of mother

 -  Active infection requiring intravenous antibiotics

 -  Known diagnosis of HIV infection

 -  Pts w history of another primary malignancy that currently requires active
 intervention

 -  Pts unwilling/unable to comply w protocol due to serious medical/psychiatric condition

 -  Pts who underwent surgical resection for GBM <2 weeks of start of treatment

 -  Pts who have received prior chemo, biologic therapy, XRT, interstitial
 brachytherapy/radiosurgery to brain