Lapatinib in Treating Patients With Recurrent Glioblastoma Multiforme

NCT00099060 | Completed Phase 1

• 3 other identifiers: I170CAN-NCIC-IND170CDR0000389155
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor

Outcome Measures

Primary Outcomes (2)

• Toxicity for phase I assessed by CTCAE v.3.0 MacDonald criteria

  7 years

• Response for phase II

  7 years

Secondary Outcomes (2)

• Correlative studies on archival tissue

  7 years

• Pharmacokinetics

  7 years

Interventions

lapatinib ditosylate DRUG

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• NCIC Clinical Trials Group: collaborator

Study Sites (6)

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

British Columbia Cancer Agency - Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

British Columbia Cancer Agency - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Margaret and Charles Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2L-4M1, Canada

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Brian A. Thiessen, MD

  British Columbia Cancer Agency

  STUDY CHAIR

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: December 8, 2004
• First Posted: December 9, 2004
• Study Start: December 1, 2004
• Primary Completion: November 1, 2007
• Study Completion: November 1, 2007
• Last Updated: January 27, 2014

Record last verified: 2012-04

Locations

CA (6)