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

Phase 2

Terminated

Conditions: Glioma
Oligodendroglioma
Astrocytoma

Interventions: Drug: Irinotecan Hydrochloride (HCI) Treatment
Drug: Continued Irinotecan Hydrochloride (HCI) Treatment

Registration Number: NCT00360828

Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Brief Summary: 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: 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

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 10

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:
1. Absolute Neutrophil Count (ANC) > 1,500
2. Platelets > 100,000
3. Serum Creatinine < 2.0
4. Serum Bilirubin < 2.0
5. Aspartamine transaminase/ Alanine transaminase (AST/ALT) < 3x normal
6. 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Irinotecan Treatment	Irinotecan Hydrochloride (HCI) Treatment	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.
Irinotecan Treatment	Continued Irinotecan Hydrochloride (HCI) Treatment	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Objective Response After 3 Cycles of Treatment	3 cycles (21 day cycles)	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.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	1 year post treatment end	Patients surviving at one year post treatment end
Overall Survival at 6 Months	6 months post treatment end	Patients surviving 6 months after treatment end
Frequency and Severity of Toxicity	3 months	Toxicities assessed through 3 months
Overall Survival at 12 Months	12 months post treatment end	Patients surviving 12 months after last dose of drug