Phase II Study of Irinotecan HCI for Recurrent Anaplastic Astrocytomas, Mixed Malignant Gliomas, and Oligodendrogliomas

Study Overview
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Brief Summary
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Phase 2 trial to explore the efficacy and safety of irinotecan (CPT-11). Also administered at each cycle was zofran/Kytril/Anzemet, decadron, and IV atropine. At each cycle, patient exams and interviews as well as lab results were to help the research team to determine the symptomatic side effects of the treatment. Recorded past toxicities were to be compared with current side effects.

Detailed Description
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Phase 2 trial to explore the efficacy and safety of irinotecan (CPT-11) in patients with recurrent anaplastic astrocytomas (AA), mixed malignant glioma, and oligodendrogliomas (OA). Patients were to be stratified by tumor histology and treated with CPT-11 every 21 days (treatment cycle). Baseline data (collected <14 days) was to consist of a neurological/oncological history, neurological examination, height, weight, performance status, Quality Of Life FACT-L questionnaire, laboratory studies to include complete blood count (CBC), differential, platelets, prothrombin time (PT), complete metabolic panel (CMP), Lactose dehydrogenase (LDH), and a pregnancy test, as well as a cranial Computerized Tomography/Magnetic Resonance Imaging (CT/MRI) with and without contrast (to measure or evaluate the size and location of the tumor before treatment). Administered every 21 days was a dose of irinotecan (CPT-11), zofran/Kytril/Anzemet, decadron, and intravenous (IV) atropine. At each cycle, patient exams and interviews as well as lab results were to help the research team to determine the symptomatic side effects of the treatment. Recorded past toxicities were to be compared with current side effects. Between days 15-21 (within 7 days of next scheduled CPT-11 treatment) the following tests were to be repeated - a neurological/oncological history and neurological examination, weight, blood drawn (CMP, LDH), performance status, and Quality Of Life FACT-L questionnaire. Also, a MRI (Cranial CT/MRI with and without contrast) was to be performed for tumor assessments at week 9, 18, 27, 36, and after every nine weeks thereafter until progression. Response was to be measured by a reduction in tumor size. These supportive therapies were provided as necessary: Antiemetic Therapy Anticholinergics Loperamide (Imodium®) Growth Factors Other Concomitant Medications

Official Title
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A Phase II Study of Irinotecan HCI in Patients With Recurrent Anaplastic Astrocytomas, Mixed Malignant Gliomas, and Oligodendrogliomas

Conditions
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Astrocytoma, Glioma, Oligodendroglioma

Intervention / Treatment
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* Drug: Irinotecan Hydrochloride (HCI) Treatment
* Drug: Continued Irinotecan Hydrochloride (HCI) Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histological or neuroradiographic documented recurrent glioma defined as an anaplastic astrocytoma, mixed malignant glioma or oligodendroglioma. All patients must have had prior pathologic confirmation of primary tumor histology. Patients must be > than or equal to 18 years old. Patients must have a Karnofsky performance score (KPS) of > or equal to 50 Measurable disease per MacDonald criteria is required Patients must have a predicted life expectancy of at least 12 weeks Required initial laboratory data: Absolute Neutrophil Count (ANC) > 1,500 Platelets > 100,000 Serum Creatinine < 2.0 Serum Bilirubin < 2.0 Aspartamine transaminase/ Alanine transaminase (AST/ALT) < 3x normal Pregnancy test for females with child-bearing potential negative Patients must sign and date an IRB approved informed consent form stating he or she is aware of the neoplastic nature of the disease. Patient must willingly provide written consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts. (Human protection committee approval of this protocol and consent form is required). Patients must be willing and able to comply with scheduled visits, treatment plan, and laboratory tests and accessible for follow-up. Patients must have been previously treated with both surgery and radiotherapy. Prior adjuvant and one salvage chemotherapy regimen is permitted. Prior stereotactic radiotherapy is permitted. Exclusion Criteria: Patients have evidence of leptomeningeal spread of disease. Patients having been treated with 2 or more salvage regimens. Pregnant or breast-feeding women. With the exception of post-menopausal or infertile women, a negative blood test for pregnancy is mandatory before entry on study. Fertile persons refusing to use adequate contraceptives may not participate. Patients with a history of irritable bowel disease, irritable bowel syndrome, chronic diarrhea or presence of a bowel obstruction. Patients with a second active malignancy or diagnosis of other cancer within 3 years of enrollment, except for surgically cured basal cell carcinoma, or in situ carcinoma of the cervix. Mentally incapacitated patients or psychiatric illness that would prevent the patient from giving informed consent. Patients with poorly controlled diabetes, hepatitis infection, uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, and myocardial infarction within the previous six months, or serious uncontrolled cardiac arrhythmia. Known to be human immunodeficiency virus (HIV) positive or to have an acquired immunodeficiency syndrome (AIDS) related illness. Patients with an active infection that is not adequately controlled with antibiotics. Patients with other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study. Patients with a known sensitivity to any of the products to be administered during treatment. Patients currently enrolled in another clinical trial or patients who have participated in a trial of an investigational device or drug within the last 30 days. Patients previously treated with CPT-11. Concurrent stereotactic radiotherapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Irinotecan Treatment<br>Participants were given irinotecan at a fixed dose: [350 mg/m2 in patients either not on anti-seizure drugs or on anti-seizure drugs which do not interfere with the metabolism of Irinotecan; 600 mg/m2 in patients on anti-seizure drugs which interfere with the metabolism of Irinotecan] once every 21 days. Depending on how many side effects were experienced with the first cycle [first 21 days], the dose of both drugs may remain the same or may be decreased to make the treatment better tolerated with less side effects. The irinotecan was given to through a vein over 90 minutes. | Drug: Irinotecan Hydrochloride (HCI) Treatment<br>* Irinotecan injections. Irinotecan hydrochloride [CPT-11; CAMPTOSAR] is an antineoplastic agent of the topoisomerase I inhibitor class. The drug is supplied in amber vials and appears as a pale yellow transparent aqueous solution. Two vial sizes are available: 2 mL vials containing 40 mg of drug and 5 mL vials containing 100 mg of drug. A treatment cycle was 21 days. Patients were treated for a minimum of 3 cycles (doses) of CPT-11 or until their disease progressed.<br>* Other names: Irinotecan HCL;Drug: Continued Irinotecan Hydrochloride (HCI) Treatment<br>* For patients responding to treatment, therapy could have continued beyond 18 cycles.<br>* Other names: Irinotecan HCL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Objective Response After 3 Cycles of Treatment | The intent was to have 63 evaluable participants to determine the Objective Response Rate utilizing Criteria for Response, Progression and Relapse according to the McDonald Criteria. A measurement is made of the maximal enhancing tumor diameter on a single axial gadolinium-enhanced T1-weighted section, and then the largest perpendicular diameter is measured on the same image. The product of the 2 diameters is calculated, and the measurements are repeated with each scan. Measurements from multiple lesions are summed. | 3 cycles (21 day cycles) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival at 6 Months | Patients surviving 6 months after treatment end | 6 months post treatment end | 
| Progression Free Survival | Patients surviving at one year post treatment end | 1 year post treatment end | 
| Frequency and Severity of Toxicity | Toxicities assessed through 3 months | 3 months | 
| Overall Survival at 12 Months | Patients surviving 12 months after last dose of drug | 12 months post treatment end | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent Anaplastic Astrocytoma, Mixed Malignant Glioma, Oligodendroglioma, Irinotecan, Brain tumor, Nitrosoureas, Brain and nervous system