NCT00979017

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
41

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Nov 2009

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 15, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 17, 2009

Completed
2 months until next milestone

Study Start

First participant enrolled

November 1, 2009

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2011

Completed
1.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2013

Completed
7 months until next milestone

Results Posted

Study results publicly available

August 12, 2013

Completed
Last Updated

March 19, 2014

Status Verified

February 1, 2014

Enrollment Period

1.3 years

First QC Date

September 15, 2009

Results QC Date

June 5, 2013

Last Update Submit

February 5, 2014

Conditions

Glioblastoma MultiformeGliosarcoma

Keywords

malignant gliomaglioblastoma multiformegliosarcomaAvastinbevacizumabTemodartemozolomideIrinotecanCPT-11Pro00019065VredenburghDuke

Outcome Measures

Primary Outcomes (1)

  • 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 (4)

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

    4 months

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

    4 months

  • Median Progression-free Survival (PFS)

    36 months

  • Median Overall Survival (OS)

    36 months

Study Arms (1)

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: AvastinDrug: TemozolomideDrug: Irinotecan

Interventions

AvastinDRUG

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

Also known as: Avastin (bevacizumab)
Avastin in combination with temozolomide and irinotecan
TemozolomideDRUG

Oral temozolomide at 200 mg/m2 daily for 5 days

Also known as: Temodar
Avastin in combination with temozolomide and irinotecan
IrinotecanDRUG

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)

Also known as: CPT-11, Camptosar
Avastin in combination with temozolomide and irinotecan

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • 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
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

  • 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.

    PMID: 26025933DERIVED

Related Links

MeSH Terms

Conditions

GlioblastomaGliosarcomaGlioma

Interventions

BevacizumabTemozolomideIrinotecan

Condition Hierarchy (Ancestors)

AstrocytomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsDacarbazineTriazenesOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsCamptothecinAlkaloids

Results Point of Contact

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

Study Officials

  • Katherine B Peters, MD, PhD

    Duke University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

September 15, 2009

First Posted

September 17, 2009

Study Start

November 1, 2009

Primary Completion

February 1, 2011

Study Completion

January 1, 2013

Last Updated

March 19, 2014

Results First Posted

August 12, 2013

Record last verified: 2014-02

Locations

US(1)