Lapatinib in Treating Young Patients With Recurrent or Refractory Central Nervous System Tumors

NCT00095940 | Completed Phase 1 Results

• 3 other identifiers: NCI-2012-03007PBTC-016U01CA081457
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies lapatinib to see how well it works in treating young patients with recurrent or refractory central nervous system (CNS) tumors. Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

Conditions

Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Ependymoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Oligodendroglioma

Outcome Measures

Primary Outcomes (2)

• Relative Phosphorylation of ERBB2 (Molecular Biology Objective)

  Lapatinib may be able to control the growth of tumor cells. To assess the ability of lapatinib to block a molecule, the ERBB2 receptor, that signals tumor cells to divide, fresh frozen tissue from the surgical resection is processed by quantitative western blot analysis to assess the phosphorylation of ERBB2. The relative phosphorylation is a ratio of the phosphorylated ERBB2 measured in the tumor normalized to the level of total receptor protein and housekeeping protein. Lower values suggests more inhibition of the ERRB2 receptor signal and a decreased ability for tumor cell division.

  7-14 days after starting therapy and prior to surgery

• Number of Participants With a Sustained Objective Response (Complete or Partial Response) (Phase II Objective)

  A complete response is defined as complete disappearance of all tumor accompanied by a stable or improving neurologic exam, and a partial response is defined as 50% or more reduction in the tumor size by bi-dimensional measurement and a stable or improving neurologic exam. The response must be sustained for at least 8 weeks. The number of patients with a sustained objective response will be reported separately for each of the three disease groups.

  From start of therapy until the earliest of disease progression, death or end of the fourth course (recurrent medulloblastoma and recurrent high grade glioma) or end of the sixth course (recurrent ependymoma)

Secondary Outcomes (4)

• Tumor to Plasma Lapatinib Concentration (Molecular Biology Objective)

  First dose of lapatinib prior to surgery

• Maximum Concentration of Lapatinib in Plasma (Phase II Objective)

  First dose of lapatinib in course 1

• Number of Participants With Tumors Expressing Total ERBB2

  Pre-treatment

• Number of Participants With Tumors Expressing Phosphorylated ERBB2 (Phase II Objective)

  Pre-treatment

Study Arms (1)

Treatment (surgery, lapatinib)

EXPERIMENTAL

Molecular Biology Phase: Patients randomized to receive lapatinib prior to surgery receive oral lapatinib twice daily for 7-14 days. Surgery is performed after 7-14 days of lapatinib treatment. For patients randomized to not receive lapatinib, surgery is performed within 3 weeks of registration. After surgical resection, all molecular biology participants start lapatinib treatment within 10 days post-surgery. The first dose of lapatinib post-surgery initiates course 1. Patients receive oral lapatinib twice daily on days 1-28. Treatment repeats every 28 days for up to 26 courses (2 years) in the absence of disease progression or unacceptable toxicity. Lapatinib Continuation/Phase II: Patients receive oral lapatinib twice daily on days 1-28. Treatment repeats every 28 days for up to 26 courses (2 years) in the absence of disease progression or unacceptable toxicity.

Drug: lapatinib ditosylate; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: positron emission tomography; Procedure: magnetic resonance imaging

Interventions

lapatinib ditosylate DRUG

Given orally

Also known as: GSK572016, GW-572016, GW2016, Lapatinib, Tykerb

Treatment (surgery, lapatinib)

therapeutic conventional surgery PROCEDURE

Undergo surgery

Treatment (surgery, lapatinib)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (surgery, lapatinib)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (surgery, lapatinib)

positron emission tomography PROCEDURE

Correlative studies

Also known as: FDG-PET, PET, PET scan, tomography, emission computed

Treatment (surgery, lapatinib)

magnetic resonance imaging PROCEDURE

Correlative studies

Also known as: MRI, NMR imaging, NMRI, nuclear magnetic resonance imaging

Treatment (surgery, 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:

• PHASE I TRIAL:
• All patients with recurrent or refractory malignant CNS tumors; a histological diagnosis of malignant CNS tumor from either the initial presentation or at the time of recurrence is required for all patients, but those with brain stem gliomas
• MOLECULAR BIOLOGY TRIAL:
• Patients must have recurrent or refractory disease with a histological diagnosis from either the initial presentation or at the time of recurrence of one of the following:
• Recurrent or refractory medulloblastoma/PNET
• Recurrent or refractory high grade glioma, (anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, anaplastic oligodendroglioma)
• Recurrent or refractory ependymoma
• Patients for whom surgical resection is clinically indicated and are amenable to receiving GW572016 for 7-14 days prior to their resection
• PHASE II TRIAL:
• Patients must have recurrent or refractory disease with a histological diagnosis from either the initial presentation or at the time of recurrence of one of the following:
• Recurrent or refractory medulloblastoma/PNET,
• Recurrent or refractory high grade glioma, (anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, anaplastic oligodendroglioma)
• Recurrent or refractory ependymoma
• Patients must have measurable disease
• Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration

You may not qualify if:

• 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 with uncontrolled infection

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Pediatric Brain Tumor Consortium

Memphis, Tennessee, 38105, United States

Location

MeSH Terms

Conditions

Astrocytoma; Familial ependymoma; Glioblastoma; Medulloblastoma; Oligodendroglioma

Interventions

Lapatinib; N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl-6-(5-((methylsulfonyl)ethyl)aminomethyl)-2-furyl)-4-quinazolinamine; Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

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; Neuroectodermal Tumors, Primitive

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Limitations and Caveats

Accrual to the Molecular Biology phase (MBP) was contingent upon accrual being open for the Phase II since some participants in the MBP could be counted in the phase II. The phase II enrolled rapidly thus limiting enrollment to the MBP.

Results Point of Contact

• Title: Assistant Director Operations and Biostatistics Center
• Organization: Pediatric Brain Tumor Consortium

dana.wallace@stjude.org

901-595-2617

Study Officials

• Maryam Fouladi

  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 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2004
• First Posted: November 9, 2004
• Study Start: October 1, 2004
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: May 23, 2014
• Results First Posted: February 6, 2012

Record last verified: 2013-01

Locations

US (1)