Avastin/Temozolomide/Irinotecan for Unresectable/Multifocal Glioblastoma Multiforme

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Katy Peters, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00979017
First received: September 15, 2009
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Glioblastoma Multiforme
Gliosarcoma
Drug: Avastin
Drug: Temozolomide
Drug: Irinotecan
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Avastin in Combination With Temozolomide and Irinotecan for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Response Rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Incidence and Severity of Central Nervous System (CNS) Hemorrhage and Systemic Hemorrhage [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
    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 Grade ≥ 4 Hematologic and ≥ Grade 3 Non-hematologic Toxicities [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
    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.

  • Median Progression-free Survival (PFS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    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.

  • Median Overall Survival (OS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 41
Study Start Date: November 2009
Study Completion Date: January 2013
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Avastin
Avastin, by intravenous infusion, 10 mg/kg every 14 days
Other Name: Avastin (bevacizumab)
Drug: Temozolomide
Oral temozolomide at 200 mg/m2 daily for 5 days
Other Name: Temodar
Drug: Irinotecan
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)
Other Name: CPT-11, Camptosar

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00979017

Locations
United States, North Carolina
The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Katy Peters
Genentech
Investigators
Principal Investigator: Katherine B Peters, MD, PhD Duke University
  More Information

Additional Information:
No publications provided

Responsible Party: Katy Peters, Assistant Professor, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00979017     History of Changes
Other Study ID Numbers: Pro00019065
Study First Received: September 15, 2009
Results First Received: June 5, 2013
Last Updated: February 5, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Duke University:
malignant glioma
glioblastoma multiforme
gliosarcoma
Avastin
bevacizumab
Temodar
temozolomide
Irinotecan
CPT-11
Pro00019065
Vredenburgh
Duke

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Anticonvulsants
Temozolomide
Dacarbazine
Irinotecan
Bevacizumab
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on April 14, 2014