Lapatinib in Treating Patients With Recurrent Glioblastoma Multiforme

This study has been completed.
Sponsor:
Collaborator:
NCIC Clinical Trials Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00099060
First received: December 8, 2004
Last updated: January 24, 2014
Last verified: April 2012
  Purpose

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of lapatinib and to see how well it works in treating patients with recurrent glioblastoma multiforme.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: lapatinib ditosylate
Phase 1
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: A Phase I/II Study of GW572016 in Patients With Recurrent Malignant Glioma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Toxicity for phase I assessed by CTCAE v.3.0 MacDonald criteria [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]
  • Response for phase II [ Time Frame: 7 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlative studies on archival tissue [ Time Frame: 7 years ] [ Designated as safety issue: No ]
  • Pharmacokinetics [ Time Frame: 7 years ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: December 2004
Study Completion Date: November 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: lapatinib ditosylate

    For patients receiving enzyme inducing anti-epileptic drugs (EIAEDs):

    • Phase I: starting dose for first cohort: 1000 mg GW572016 po b.i.d.; actual dose assigned at registration; intra patient dose escalation permitted ONCE in phase I patients ONLY if specified criteria met (see section 8.6).
    • Phase II: Recommended phase II dose from phase I portion of the study, given po b.i.d.

    For patients NOT receiving enzyme inducing anti-epileptic drugs (NON-EIAEDs):

    • Phase II: 750 mg GW572016 po b.i.d.

    For all patients:

    • Dose reductions as required based on adverse events.

Detailed Description:

OBJECTIVES:

Phase I

  • Determine the maximum tolerated dose and recommended phase II dose of lapatinib in patients with recurrent malignant glioblastoma multiforme who are taking CYP3A4 enzyme-inducing anti-epileptic drugs (EIAEDs).
  • Determine the toxic effects of this drug in these patients.
  • Determine the pharmacokinetics of this drug in these patients.

Phase II

  • Determine the efficacy of this drug, in terms of objective tumor response rate, in patients who are taking EIAEDs and in those who are not taking EIAEDs.
  • Correlate immunohistochemical measures of cellular proteins and receptors from tumor samples with anti-tumor activity of this drug in these patients.
  • Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a multicenter, open-label, phase I, dose-escalation study followed by a phase II study.

  • Phase I: Patients receive oral lapatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of lapatinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive lapatinib as in phase I at the MTD. Patients are followed at 1 month and then periodically for survival. Patients with stable or responding disease who go off therapy are followed every 3 months for up to one year and then periodically thereafter for survival.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for the phase I portion of this study within 18 months. A total of 15-30 patients will be accrued for the phase II portion of this study within 18 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignant glioblastoma multiforme
  • Recurrent or progressive disease after prior primary treatment with radiotherapy with or without adjuvant chemotherapy
  • Bidimensionally measurable disease on CT scan or MRI with at least one lesion ≥ 1 cm x 1 cm
  • Paraffin embedded tumor sample available
  • Concurrent enzyme-inducing anti-epileptic drugs (EIAEDs) required for phase I of the study

    • Patients in phase II of the study may or may not be receiving EIAEDs

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Bilirubin ≤ upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN

Renal

  • Creatinine ≤ 1.5 times ULN

Cardiovascular

  • LVEF ≥ 50% by echocardiogram or MUGA
  • No myocardial infarction within the past 6 months
  • No congestive heart failure
  • No unstable angina
  • No active cardiomyopathy
  • No cardiac arrhythmia
  • No uncontrolled hypertension

Pulmonary

  • No pulmonary disease requiring oxygen

Neurologic

  • No preexisting peripheral neuropathy ≥ grade 3
  • No history of significant neurologic disorder that would preclude study compliance or ability to give informed consent

Gastrointestinal

  • No upper gastrointestinal or other conditions that would preclude compliance with oral medication
  • No active peptic ulcer disease

Other

  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumor
  • No immune deficiency
  • No history of significant psychiatric disorder (e.g., uncontrolled psychotic disorders) that would preclude study compliance or ability to give informed consent
  • No other serious illness or medical condition that would preclude study participation
  • No known hypersensitivity to compounds of similar chemical or biological composition to lapatinib
  • No active uncontrolled or serious infection
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent prophylactic filgrastim (G-CSF), sargramostim (GM-CSF), or other hematopoietic growth factors

    • Concurrent hematopoietic growth factors allowed for treatment of acute toxicity (e.g., febrile neutropenia)

Chemotherapy

  • See Disease Characteristics
  • No prior chemotherapy for recurrent disease
  • No more than one prior chemotherapy regimen in the adjuvant setting

    • At least 6 months since prior adjuvant chemotherapy

Endocrine therapy

  • Concurrent steroids allowed provided the dose is stable for at least 14 days before study entry

Radiotherapy

  • See Disease Characteristics
  • At least 6 weeks since prior radiotherapy

Surgery

  • At least 2 weeks since prior major surgery

Other

  • H2 blockers and proton pump inhibitors allowed, unless they are CYP3A4 inducers or inhibitors
  • At least 7 days since prior and no concurrent administration of any of the following CYP3A4 inhibitors:

    • Clarithromycin
    • Erythromycin
    • Troleandomycin
    • Telithromycin
    • Ciprofloxacin
    • Norfloxacin
    • Itraconazole
    • Ketoconazole
    • Voriconazole
    • Fluconazole (≤150 mg/day allowed)
    • Nefazodone
    • Fluovoxamine
    • Delavirdine
    • Nelfinavir
    • Amprenavir
    • Ritonavir
    • Indinavir
    • Saquinavir
    • Lopinavir
    • Verapamil
    • Diltiazem
    • Aprepitant
    • Grapefruit or grapefruit juice
    • Bitter orange
  • At least 14 days since prior and no concurrent administration of any of the following CYP3A4 inducers:

    • Rifampin
    • Rifabutin
    • Rifapentine
    • Efavirenz
    • Nevirapine
    • Hypericum perforatum (St. John's wort)
    • Modafinil
  • At least 6 months since prior and no concurrent administration of amiodarone
  • Antacids (e.g., mylanta, maalox, tums, rennies) must be administered ≥ 1 hour before and ≥ 1 hour after study drug
  • At least 2 days since prior and no concurrent cimetidine
  • No other concurrent anti-cancer agents
  • No other concurrent investigational therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00099060

Locations
Canada, Alberta
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada, T2N 4N2
Canada, British Columbia
British Columbia Cancer Agency - Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Margaret and Charles Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, Canada, H2L-4M1
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Brian A. Thiessen, MD British Columbia Cancer Agency
  More Information

Additional Information:
No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00099060     History of Changes
Other Study ID Numbers: I170, CAN-NCIC-IND170, CDR0000389155
Study First Received: December 8, 2004
Last Updated: January 24, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
adult giant cell glioblastoma
adult gliosarcoma
recurrent adult brain tumor

Additional relevant MeSH terms:
Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Lapatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014