Panitumumab and Irinotecan for Malignant Gliomas
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).
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Panitumumab in Combination With Irinotecan for Malignant Gliomas|
- 6-month Progression-free Survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause. Macdonald criteria are standard criteria in neuro-oncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of: 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), and 3) concomitant steroid use (as reported by the investigator).
- One-Year Overall Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]Percentage of participants surviving 12 months from the start of study treatment. OS was defined as the time from the date of study treatment initiation to the date of the death due to any cause.
- Safety of Panitumumab in Combination With Irinotecan [ Time Frame: 16 months ] [ Designated as safety issue: Yes ]Number of participants experiencing a toxicity ≥ grade 3 as graded per CTCAE v.3.0
- Effect of Panitumumab in Combination With Irinotecan on Corticosteroid Dose [ Time Frame: Baseline and Day 29 ] [ Designated as safety issue: No ]Average change in corticosteroid dose from baseline to the end of cycle 1.
- Relationship Between Epidermal Growth Factor Receptor (EGF-R) Mutational Analysis and Efficacy or Toxicity [ Time Frame: 16 months ] [ Designated as safety issue: No ]Number of participants with an abnormal fluorescence in situ hybridization (FISH) interpretation that 1) survived < 6 months and 2) experienced a ≥ grade 3 toxicity as graded per CTCAE v.3.0
- Objective Response Rate [ Time Frame: 16 months ] [ Designated as safety issue: No ]Number of participants with an objective response (complete response or partial response) based on modified Macdonald criteria. A complete response is defined as the disappearance of all enhancing rumor and mass effect, off all corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks. A partial response is defined as greater than or equal to 50% reduction in tumor size on MR (magnetic resonance) / CT(computed tomography) by bi-dimensional measurement on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks.
- Median Overall Survival (OS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]Time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.
|Study Start Date:||February 2010|
|Study Completion Date:||October 2011|
|Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|
|Experimental: Panitumumab and irinotecan||
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.
Other Names:Drug: Panitumumab
Panitumumab, 6 mg/kg, as an intravenous infusion every other week. Treatment on both drugs will continue until tumor progression or unacceptable toxicity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01017653
|United States, North Carolina|
|The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Annick Desjardins, MD, FRCPC||Duke University|