Bevacizumab and Irinotecan in Treating Young Patients With Recurrent, Progressive, or Refractory Glioma, Medulloblastoma, Ependymoma, or Low Grade Glioma

NCT00381797 | Completed Phase 2 Results DMC

• 4 other identifiers: NCI-2009-01090PBTC-022CDR0000499832U01CA081457
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 11

Brief Summary

This phase II trial is studying how well giving bevacizumab together with irinotecan works in treating young patients with recurrent, progressive, or refractory glioma, medulloblastoma, ependymoma, or low grade glioma. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of glioma by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with irinotecan may kill more tumor cells.

Conditions

Childhood Cerebral Anaplastic Astrocytoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate Sustained for ≥ 8 Weeks

  Objective response is either a complete response or a partial response observed during the first four courses of treatment and sustained for 8 weeks. The objective response rate will be reported separately for patients with recurrent/progressive malignant glioma(Stratum A), recurrent/progressive instrinsic brain stem tumors(Stratum B), recurrent/progressive medulloblastoma(Stratum C), and recurrent/progressive ependymoma(Stratum D). CR is complete disappearance of all enhancing tumor. PR is \>= 50% reduction in tumor size. This outcome measures is not defined for the Stratum E in the protocol.

  From day 1 of treatment up to 24 weeks

• Sustained Disease Stabilization Rate Associated With Bevacizumab and Irinotecan in Patients With Recurrent or Progressive Low-grade Glioma (Stratum E)

  Disease stabilization is defined as a complete response(CR) or partial response(PR) observed during the first four courses and sustained for 8 weeks; or stable disease (SD) sustained for 6 courses characterized by SD at the end of course 2, at the end of course 4 and at the end of course 6. CR is complete disappearance of all enhancing tumor. PR is \>= 50% reduction in tumor size. SD is at least stable and maintenance corticosteroid dose not increased in neurologic examination.

  From day 1 of treatment up to 24 weeks

Secondary Outcomes (25)

• Number of Study Participants With Grade 3 or 4 Treatment-related Toxicity

  From day 1 of treatment until off study

• Cumulative Incidence of Sustained Objective Responses

  From the first imaging after treatment up to 2 years

• Progression-free Survival

  From start of treatment up to 2 years

• Change in Perfusion Ratio Between the Baseline and Day 15 Brain Imaging

  Baseline and day 15

• Change in Diffusion Ratio Between the Baseline and Day 15 Brain Image

  Baseline and day 15

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and irinotecan hydrochloride IV over 90 minutes on day 16 or 17 for course 1. Patients receive bevacizumab and irinotecan hydrochloride on days 1 and 15 for all subsequent courses. Treatment repeats every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Patients undergo MRIs of the brain, magnetic resonance perfusion/diffusion, and fludeoxyglucose F 18 positron emission tomography at baseline and periodically during treatment.

Biological: Bevacizumab; Radiation: Fludeoxyglucose F-18; Drug: Irinotecan Hydrochloride

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar FKB238, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF

Arm I

Fludeoxyglucose F-18 RADIATION

Undergo fludeoxyglucose F18 PET

Also known as: 18FDG, FDG, fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18

Arm I

Irinotecan Hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, U-101440E

Arm I

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Histologically confirmed high-grade glioma (WHO grade III or IV) at any site within the brain, including the following:
• Anaplastic astrocytoma
• Glioblastoma multiforme (including giant cell and gliosarcoma subtypes)
• Anaplastic oligodendroglioma
• Anaplastic ganglioglioma
• Anaplastic oligoastrocytoma
• Diffuse brain stem glioma
• Histologic confirmation not required
• Histologically confirmed medulloblastoma
• Histologically confirmed ependymoma
• Primary spinal cord malignant glioma with measurable metastatic disease within the brain
• Histologic confirmation required
• Neuraxis dissemination allowed provided there is bidimensionally measurable disease within the brain and spinal cord
• Low grade glioma at any site within the brain with or without spinal cord disease
• Recurrent, progressive, or refractory disease (must have received prior chemoradiotherapy)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (11)

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Pediatric Brain Tumor Consortium

Memphis, Tennessee, 38105, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• Han K, Peyret T, Quartino A, Gosselin NH, Gururangan S, Casanova M, Merks JH, Massimino M, Grill J, Daw NC, Navid F, Jin J, Allison DE. Bevacizumab dosing strategy in paediatric cancer patients based on population pharmacokinetic analysis with external validation. Br J Clin Pharmacol. 2016 Jan;81(1):148-60. doi: 10.1111/bcp.12778. Epub 2015 Dec 10.

  PMID: 26345283 BACKGROUND

Related Links

• Bevacizumab dosing strategy in paediatric cancer patients based on population pharmacokinetic analysis with external validation

MeSH Terms

Conditions

Oligodendroglioma; Spinal Cord Neoplasms; Familial ependymoma; Medulloblastoma

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Fluorodeoxyglucose F18; Irinotecan

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroectodermal Tumors, Primitive

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Deoxyglucose; Deoxy Sugars; Carbohydrates; Camptothecin; Alkaloids; Heterocyclic Compounds

Limitations and Caveats

Neuroimaging data capturing Volume Enhancing and Perfusion Ratio was so limited to run any statistical model. Similarly, due to limited data, some PK and Biology objectives were not able to be addressed.

Results Point of Contact

• Title: Shengjie Wu
• Organization: St. Jude Children's Research Hospital

shengjie.wu@stjude.org

(901) 595-2859

Study Officials

• Sridharan Gururangan

  Pediatric Brain Tumor Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2006
• First Posted: September 28, 2006
• Study Start: August 1, 2006
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: November 28, 2017
• Results First Posted: January 15, 2013

Record last verified: 2017-10

Locations

US (11)