Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Glioma

Gliosarcoma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anticonvulsants

Irinotecan

Bevacizumab

Temozolomide

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Avastin 10 mg/kg every 14 days. Temozolomide 200 mg/m2 daily x 5 days in a 28-day cycle. Irinotecan dose depends on whether the patient is on an enzyme-inducing antiepileptic drug (EIAED). EIAED 340 mg/m2 every other week and no EIAED 125 mg/m2 every other week. Irinotecan dose also depends on if the patient has the UGT 1A1 polymorphism (7/7). If so, they do not metabolize the irinotecan normally, so these patients will start out at a two dose level reduction. EIAED starting dose will be 275 mg/m2 and no EIAED starting dose will be 75 mg/ m2.

Avastin, by intravenous infusion, 10 mg/kg every 14 days

Avastin

Oral temozolomide at 200 mg/m2 daily for 5 days

Irinotecan, by intravenous infusion, every other week (dose dependent upon if taking enzyme-inducing anti-epileptic drugs or if a blood test indicates the patient has the UGT 1A1 polymorphism)

Katherine B Peters, MD, PhD

The primary objective of the study is to determine the efficacy of Avastin in combination with temozolomide and irinotecan in terms of response rate. The secondary objectives are to describe the overall and progression-free survivals of unresectable patients treated with upfront Avastin, temozolomide and irinotecan and to assess the safety of Avastin, temozolomide and irinotecan in unresectable glioblastoma patients.

This is a phase II study with the combination of Avastin, temozolomide and irinotecan for unresectable or multifocal World Health Organization (WHO) grade IV malignant glioma patients. Patients will receive up to four cycles of Avastin, temozolomide and irinotecan. Approximately 41 subjects will take part in this study at Duke.

Avastin/Temozolomide/Irinotecan for Unresectable/Multifocal Glioblastoma Multiforme

Avastin in Combination With Temozolomide and Irinotecan for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas

The percentage of participants with a complete or partial response as determined by a modification of the Response Assessment in Neuro-Oncology (RANO) criteria. Complete Response (CR) was defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses) and accompanied by a stable or improving neurologic examination. Partial Response (PR) was defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids and accompanied by a stable or improving neurologic examination. Per the criteria, confirmation of response was required. Response rate = CR+PR.

Incidence and severity of CNS hemorrhage and systemic hemorrhage- The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.

Incidence of treatment-related, grade ≥ 4 hematologic and ≥ grade 3 non-hematologic toxicities- The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.

Time in months from the start of study treatment to the date of first progression according to RANO criteria, or to death due to any cause. Per RANO, progression is a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions, worsening T2/FLAIR, any new lesion, or clinical deterioration. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.

Time in months from the start of study treatment to the 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.

Genentech, Inc.

Katy Peters

Assistant Professor

The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.

Avastin 10 mg/kg every 14 days. Temozolomide 200 mg/m2 daily x 5 days in a 28-day cycle. Irinotecan dose depends on whether the patient is on an enzyme-inducing antiepileptic drug (EIAED). EIAED 340 mg/m2 every other week and no EIAED 125 mg/m2 every other week. Irinotecan dose also depends on if the patient has the UGT 1A1 polymorphism (7/7). If so, they do not metabolize the irinotecan normally, so these patients will start out at a two dose level reduction. EIAED starting dose will be 275 mg/m2 and no EIAED starting dose will be 75 mg/ m2.

Avastin in combination with temozolomide and irinotecan : Avastin, by intravenous infusion, 10 mg/kg every 14 days in combination with oral temozolomide at 200 mg/m2 daily for 5 days and irinotecan, by intravenous infusion, every other week (dose dependent upon if taking enzyme-inducing anti-epileptic drugs or if a blood test indicates the patient has the UGT 1A1 polymorphism)

Avastin in Combination With Temozolomide and Irinotecan

Age, Continuous

Sex: Female, Male

Katherine B. Peters, MD, PhD

Response Rate

CNS hemorrhage (grade 3)

Systemic hemorrhage (all grade 3)

Incidence and Severity of Central Nervous System (CNS) Hemorrhage and Systemic Hemorrhage

Grade > or = to 4 hematologic toxicity

Grade > or = to 3 non-hematologic toxicity

Incidence of Grade ≥ 4 Hematologic and ≥ Grade 3 Non-hematologic Toxicities

Median Progression-free Survival (PFS)

Median Overall Survival (OS)

Overall Study

Panitumumab

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.

Panitumumab, 6 mg/kg, as an intravenous infusion every other week. Treatment on both drugs will continue until tumor progression or unacceptable toxicity.

Annick Desjardins, MD, FRCPC

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).

Panitumumab and Irinotecan for Malignant Gliomas

Phase II Study of Panitumumab in Combination With Irinotecan for Malignant Gliomas

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).

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.

Number of participants experiencing a toxicity ≥ grade 3 as graded per CTCAE v.3.0

Average change in corticosteroid dose from baseline to the end of cycle 1.

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

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.

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.

Amgen

Annick Desjardins

Assist Professor of Medicine-Neurology

The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov

Panitumumab in Combination with Irinotecan : Panitumumab, 6mg/kg, as an intravenous infusion every other week in combination with Irinotecan (dose dependent upon whether the patient is taking an enzyme-inducing anti-epileptic drug \[EIAED\]). On an enzyme-inducing anti-epileptic drug (EIAED), irinotecan will be dosed at 340 mg/m2 every other week. Not on an EIAED, irinotecan will be dosed at 125 mg/m2. Treatment will continue until tumor progression or unacceptable toxicity.

Panitumumab and Irinotecan

Age Continuous

6-month Progression-free Survival (PFS)

One-Year Overall Survival

Safety of Panitumumab in Combination With Irinotecan

Insufficient data to analyze the effect of the treatment regimen on corticosteroid dose. Data was not collected for this outcome.

Effect of Panitumumab in Combination With Irinotecan on Corticosteroid Dose

Abnormal FISH Interpretation & Survived <6 months

Abnormal FISH Interpretation & ≥ grade 3 toxicity

Insufficient data to analyze the relationship between EGF-R analysis and efficacy or toxicity. Data was not collected for this outcome.

Relationship Between Epidermal Growth Factor Receptor (EGF-R) Mutational Analysis and Efficacy or Toxicity

2 patients' response was unknown due to withdrawal from the study before an MRI was performed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Avastin/Temozolomide/Irinotecan for Unresectable/Multifocal Glioblastoma Multiforme	NCT00979017	Glioblastoma Mu... Gliosarcoma	Avastin Temozolomide Irinotecan	18 Years -	Duke University
Panitumumab and Irinotecan for Malignant Gliomas	NCT01017653	Malignant Gliom...	Irinotecan Panitumumab	18 Years -	Duke University

Spots Global Cancer Trial Database for vredenburgh

Every month we try and update this database with for vredenburgh cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for vredenburgh

Every month we try and update this database with for vredenburgh cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for vredenburgh cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.