Avastin/Temozolomide/Irinotecan for Unresectable/Multifoc... | NCT00979017

NCT00979017

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Genentech, Inc.	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Avastin in combination with temozolomide and irinotecan	Experimental	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.	Drug: Avastin Drug: Temozolomide Drug: Irinotecan

Name	Type	Description	Arm Group Labels	Other Names
Avastin	Drug	Avastin, by intravenous infusion, 10 mg/kg every 14 days	Avastin in combination with temozolomide and irinotecan

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Response Rate	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.	4 months

Secondary Outcomes

Measure	Description	Time Frame
Incidence and Severity of Central Nervous System (CNS) Hemorrhage and Systemic Hemorrhage	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.	4 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients must have histologically confirmed diagnosis of WHO grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients will be unresectable or have multifocal disease.
Age > or = to 18 years and a life expectancy of >12 weeks.
Evidence of measurable primary Central Nervous System (CNS) neoplasm on contrast enhanced MRI.
An interval of at least one week between prior biopsy or four weeks from surgical resection and enrollment on this protocol.
Karnofsky > or = to 60%.
Hemoglobin > or = to 9g/dl, absolute neutrophil count (ANC) > or = to 1,500 cells/microliter, platelets > or = to 125,000 cells/microliter.
Serum creatinine ≤ 1.5 mg/dl, serum serum glutamic oxaloacetic transaminase (SGOT) and direct bilirubin ≤ 1.5 times upper limit of normal (if the total bilirubin is greater than or equal to 1.5 x the upper limit of normal, then the direct bilirubin must be ≤ 1.5 x the upper limit of normal).
Signed informed consent approved by the Institutional Review Board prior to patient entry.
If sexually active, patients will take contraceptive measures for the duration of the treatments.

Exclusion Criteria:

Pregnancy or breast feeding
Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.
Active infection requiring IV antibiotics.
Treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the grade of the tumor.
Evidence of > grade 1 CNS hemorrhage on baseline MRI or CT scan.

Avastin-specific Exclusion Criteria:

Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
Any prior history of hypertensive crisis or hypertensive encephalopathy
New York Heart Association (NYHA) Grade II or greater congestive heart failure
History of myocardial infarction or unstable angina within 6 months prior to study enrollment
History of stroke or transient ischemic attack within 6 months prior to study enrollment
Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
Symptomatic peripheral vascular disease
Evidence of bleeding diathesis or coagulopathy
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
Serious, non-healing wound, ulcer, or bone fracture
Proteinuria at screening as demonstrated by either urine protein:creatinine (UPC) ratio > or = to 1.0 at screening OR urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
Known hypersensitivity to any component of Avastin
Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential

Name	Affiliation	Role
Katherine B Peters, MD, PhD	Duke University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center		Durham	North Carolina	27710	United States

PubMed Identifier	Type	Citation	Retractions
26025933	Derived	Peters KB, Lou E, Desjardins A, Reardon DA, Lipp ES, Miller E, Herndon JE 2nd, McSherry F, Friedman HS, Vredenburgh JJ. Phase II Trial of Upfront Bevacizumab, Irinotecan, and Temozolomide for Unresectable Glioblastoma. Oncologist. 2015 Jul;20(7):727-8. doi: 10.1634/theoncologist.2015-0135. Epub 2015 May 29.

Label	URL
The Preston Robert Tisch Brain Tumor Center	View source

Arm/Group Information

ID	Title	Description
FG000	Avastin in Combination With Temozolomide and Irinotecan	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)

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Avastin in Combination With Temozolomide and Irinotecan	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)

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Response Rate

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.

Intent-to-treat

Posted

Number

95% Confidence Interval

percentage of participants

4 months

ID	Title	Description
OG000	Avastin in Combination With Temozolomide and Irinotecan

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Avastin in Combination With Temozolomide and Irinotecan	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)

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Upper gastrointestinal hemorrhage	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment

Title	Organization	Phone	Extension	Email
Katherine B. Peters, MD, PhD	Duke University Medical Center, The Preston Robert Tisch Brain Tumor Center	(919) 684-6173		katherine.peters@duke.edu

ID	Term
D005909	Glioblastoma
D018316	Gliosarcoma
D005910	Glioma

ID	Term
D001254	Astrocytoma
D018302	Neoplasms, Neuroepithelial
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal

ID	Term
D000068258	Bevacizumab
D000077204	Temozolomide
D000077146	Irinotecan

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins

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)