Bevacizumab and Lapatinib in Children With Recurrent or Refractory Ependymoma

NCT00883688 | Completed Phase 2 Results

• 2 other identifiers: CERN08-01NCI-2012-02129
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 6

Brief Summary

The goal of this clinical research study is to learn if the combination of Avastin (bevacizumab) and Tykerb (lapatinib) can help to control ependymoma in pediatric patients. The safety of this drug combination will also be studied.

Conditions

Brain Cancer; Pediatric Cancers

Keywords

Brain Tumor; Recurrent Ependymoma; Refractory Ependymoma; Intracranial ependymoma; Ependymoblastoma; Subependymoma; Myxopapillary; Clear cell; Anaplastic; Bevacizumab; Avastin; Anti-VEGF Monoclonal Antibody; rhuMAb-VEGF; Lapatinib; Tykerb; GW572016

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective response rate defined as number of participants out of total participants with complete response plus partial response (CR+PR) sustained for at least four weeks. Complete Response (CR) - Complete disappearance on magnetic resonance imaging (MRI) of all enhancing tumor and mass effect, on a stable or decreasing dose of corticosteroids (or receiving only adrenal replacement doses), accompanied by a stable or improving neurologic examination and must be sustained for at least 4 weeks. If cerebrospinal fluid (CSF) for presence of disease was positive it must become negative. Partial Response (PR) - Greater than or equal to 50% reduction in tumor size by bi-dimensional measurement on a stable or decreasing dose of corticosteroids, accompanied by stable or improving neurological examination and must be sustained for at least 4 weeks.

  4 weeks following treatment, repeat assessments up to one year.

Study Arms (1)

Bevacizumab + Lapatinib

EXPERIMENTAL

Bevacizumab 10 mg/kg given by vein over 90 minutes for first injection (30-60 minutes for subsequent doses) every 2 weeks while on study (2 times during each 4-week "study cycle"). Lapatinib Pills of 700 mg/m\^2/dose given orally 2 times each day.

Drug: Bevacizumab; Drug: Lapatinib

Interventions

Bevacizumab DRUG

10 mg/kg given by vein over 90 minutes for first injection (30-60 minutes for subsequent doses) every 2 weeks while on study (2 times during each 4-week "study cycle").

Also known as: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

Bevacizumab + Lapatinib

Lapatinib DRUG

Pills of 700 mg/m\^2/dose given orally 2 times each day.

Also known as: Tykerb, GW572016

Bevacizumab + Lapatinib

Eligibility Criteria

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

You may qualify if:

• Age: Patient must be \< or = 21 years of age.
• Tumor: Patients must have recurrent or refractory intracranial ependymoma (including myxopapillary, clear cell, papillary, tanycytic, and anaplastic ependymoma) or subependymoma. Patients with primary diagnosis of intracranial ependymoma with spinal cord metastases or relapse are eligible. The diagnosis must be confirmed by the CERN enrolling site's pathologist on tissue from either the initial presentation or time of recurrence prior to registration. For central pathology review and trial biological studies, submission of a paraffin block with tumor measuring at least 1 cm x 1 cm in area is preferred, but 15 x 5micro m unstained sections on slides may be provided by the referring laboratory instead. Tissue must be submitted within 60 days after enrollment for central processing and analysis.
• Patients must have measureable disease which is defined as at least one measurable lesion that can be accurately measured in 2 planes. Diffuse leptomeningeal involvement ("sugar coating") that does not allow measurement of at least one lesion in 2 planes will not be considered measurable disease.
• Patients may have had any number of prior treatment regimens (including biologic) before or after radiotherapy. Patients may not have previously been treated with Bevacizumab or Lapatinib. Gliadel wafers must be approved by CERN PI (Project Leader, Co-Leader and Protocol PI).
• Neurological Deficits: Patients with neurological deficits should have deficits that are stable or improving for a minimum of 1 week prior to registration.
• Performance Score: Karnofsky Performance Scale (KPS for \> 16 years of age) or Lansky Performance Score (LPS for \< or = 16 years of age) \> or = 50 assessed within 2 weeks prior to registration.
• Evidence of recovery from any prior chemotherapy. No myelosuppressive anticancer chemotherapy or biological therapy within 3 weeks (6 weeks if a nitrosourea or mitomycin C agent) prior to registration.
• Prior/Concurrent Therapy: external beam radiation therapy (XRT): Patients must have had prior radiation therapy for treatment of their ependymoma. XRT must be \> or = 3 months prior to registration for craniospinal irradiation (\> or = 18 Gy); \> or = 4 weeks for local radiation to primary tumor; and \> or = 2 weeks prior to registration for focal irradiation to symptomatic metastatic sites.
• Prior/Concurrent Therapy: Bone Marrow Transplant: \> or = 3 months prior to registration for autologous bone marrow/stem cell transplant.
• Prior/Concurrent Therapy: Anti-convulsants: Patients with seizure disorder may be enrolled if well controlled. Patients receiving enzyme-inducing anticonvulsants are not eligible for this study. Patients must be off EIACD for at least 2 weeks prior to registration.
• Prior/Concurrent Therapy: Corticosteroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to registration.
• Prior/Concurrent Therapy: Growth Factors: Off all colony forming growth factor(s) \> or = 2 weeks prior to registration (G-CSF, GM-CSF, Erythropoietin).
• Patients must not have received: cytochrome P450 3A4 (CYP3A4) inhibitors within seven (7) days prior to registration on protocol and for the duration of the study. However, amiodarone, another CYP3A4 inhibitor, should have been discontinued 6 months prior to registration and for the duration of the study.
• Patient must not have received: CYP3A4 inducers within fourteen (14) days prior to registration and for the duration of the study.
• Patient must not have received: Cimetidine within 48 hours prior and for the duration of the study.

You may not qualify if:

• Patients may not have previously been treated with Bevacizumab or Lapatinib.
• Patients with any significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
• Patients with any disease that would obscure toxicity or dangerously alter drug metabolism.
• Patients receiving any other anticancer or experimental drug therapy.
• Patients with uncontrolled infection.
• Patients on enzyme inducing anticonvulsants.
• Patients with \> / = Grade 2 uncontrolled hypertension.
• History of a stroke, myocardial infarction, or unstable angina in the previous 6 months.
• Evidence of a bleeding diathesis, coagulopathy or PT international normalized ratio (INR)\>1.5.
• Patients who require the use of therapeutic anti-coagulation: except as required to maintain patency of preexisting permanent vascular catheter.
• Pre-existing coagulopathy or thrombosis: Patients must not have been previously diagnosed with a deep venous or arterial thrombosis (including pulmonary embolism), and must not have a known thrombophilic condition.
• Patients must have recovered from any surgical procedure before enrolling on this study.
• History of an abdominal fistula, GI perforation, or intra-abdominal abscess within previous 6 months.
• A serious, non healing wound, ulcer, or bone fracture.
• Evidence of a new intracranial or intratumoral hemorrhage that is larger than a punctuate size on baseline MRI obtained within 14 days prior to study registration.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• CERN Foundation - Collaborative Ependymoma Research Network: collaborator

Study Sites (6)

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Brain Neoplasms; Ependymoma; Neuroectodermal Tumors, Primitive; Glioma, Subependymal

Interventions

Bevacizumab; Lapatinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: MD Anderson Multicenter coordinating for Collaborative Ependymoma Research Network Study (CERN)
• Organization: The University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

Study Officials

• Michael E. Rytting, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: April 17, 2009
• First Posted: April 20, 2009
• Study Start: July 1, 2009
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: August 26, 2020
• Results First Posted: August 26, 2020

Record last verified: 2020-08

Locations

US (6)