Lapatinib in Treating Patients With Recurrent Glioblastoma Multiforme

Brain and Central Nervous System Tumors Clinical Trial

Official title:

A Phase I/II Study of GW572016 in Patients With Recurrent Malignant Glioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00099060
• Other study ID #: I170
• Secondary ID: CAN-NCIC-IND170C
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 8, 2004
• Last updated: January 24, 2014
• Start date: December 2004
• Est. completion date: November 2007

Study information

• Verified date: April 2012
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 2007
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	British Columbia Cancer Agency - Centre for the Southern Interior	Kelowna	British Columbia
Canada	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	British Columbia Cancer Agency - Vancouver Cancer Centre	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Canadian Cancer Trials Group

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity for phase I assessed by CTCAE v.3.0 MacDonald criteria		7 years	Yes
Primary	Response for phase II		7 years	No
Secondary	Correlative studies on archival tissue		7 years	No
Secondary	Pharmacokinetics		7 years	No