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

• ClinicalTrials.gov Identifier: NCT00360828
• Recruitment Status: Terminated
• First Posted: August 7, 2006
• Results First Posted: December 9, 2011
• Last Update Posted: March 23, 2017
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Astrocytoma; Glioma; Oligodendroglioma	Drug: Irinotecan Hydrochloride (HCI) Treatment; Drug: Continued Irinotecan Hydrochloride (HCI) Treatment	Phase 2

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Phase II Study of Irinotecan HCI in Patients With Recurrent Anaplastic Astrocytomas, Mixed Malignant Gliomas, and Oligodendrogliomas
• Study Start Date: February 2006
• Actual Primary Completion Date: October 2010
• Actual Study Completion Date: October 2010

Arms and Interventions

Arm

Intervention/treatment

Experimental: Irinotecan 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.

Drug: Irinotecan Hydrochloride (HCI) Treatment; 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.; Other Names: CPT-11; CAMPTOSAR; Irinotecan HCL; Drug: Continued Irinotecan Hydrochloride (HCI) Treatment; For patients responding to treatment, therapy could have continued beyond 18 cycles.; Other Names: CPT-11; CAMPTOSAR; Irinotecan HCL

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Objective Response After 3 Cycles of Treatment [ Time Frame: 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 :

1. Overall Survival at 6 Months [ Time Frame: 6 months post treatment end ]
   Patients surviving 6 months after treatment end
2. Progression Free Survival [ Time Frame: 1 year post treatment end ]
   Patients surviving at one year post treatment end
3. Frequency and Severity of Toxicity [ Time Frame: 3 months ]
   Toxicities assessed through 3 months
4. Overall Survival at 12 Months [ Time Frame: 12 months post treatment end ]
   Patients surviving 12 months after last dose of drug

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Florida

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States, 33612

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Investigators

• Principal Investigator: Edward Pan, MD; H. Lee Moffitt Cancer Center and Research Institute

More Information

Additional Information:

Moffitt Cancer Center Clinical Trials Website 

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT00360828
• Other Study ID Numbers: MCC-14633
• First Posted: August 7, 2006
• Results First Posted: December 9, 2011
• Last Update Posted: March 23, 2017
• Last Verified: November 2011

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:

Recurrent Anaplastic Astrocytoma; Mixed Malignant Glioma; Oligodendroglioma; Irinotecan; Brain tumor; Nitrosoureas; Brain and nervous system

Additional relevant MeSH terms:

Glioma; Astrocytoma; Oligodendroglioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Irinotecan; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents