Lapatinib Ditosylate Before Surgery in Treating Patients With Recurrent High-Grade Glioma

NCT02101905 | Completed Phase 1

• 4 other identifiers: NCI-2014-00634ABTC-1302U01CA137443UM1CA137443
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 12

Brief Summary

This pilot phase I clinical trial studies how well lapatinib ditosylate before surgery works in treating patients with high-grade glioma that has come back after a period of time during which the tumor could not be detected. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Oligodendroglioma; Gliosarcoma; Mixed Glioma; Recurrent Adult Brain Neoplasm; Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (2)

• To Determine the Lapatinib Ditosylate Intratumoral Concentration (Pharmacokinetics)

  4 pk samples obtained: pretreatment, pre-surgery, post-surgery and interpolated pre-surgery each subject received 2500mg twice a day for two days.

  Baseline and day of surgery

• To Determine the Ratio of Phosphorylated (p)EGFR/Total EGFR (PD) in Tumor Tissue

  A ratio of pEGFR/total EGFR at 80% reduction from a median value from the untreated reference group will be considered as the putative threshold to qualify a near complete inhibition of EGFR (at 80%).

  Day of surgery

Secondary Outcomes (6)

• Incidence of Adverse Events (AEs)

  Up to day 30

• Inhibition of tumor cell proliferation (KI-67)

  Inhibition of Tumor Cell Proliferation (KI-67)

• Ex-vivo Sensitivity of Tumor Sphere Cultures to Lapatinib Ditosylate

  Day of surgery

• Objective Response Rate

  Up to 2 years

• Overall Survival

  From the date of treatment start to the date of death, assessed up to 2 years

Study Arms (2)

Group A (lapatinib ditosylate, surgery)

EXPERIMENTAL

Patients receive lapatinib ditosylate PO BID on days -2 to 0. Within 3-5 hours after last dose of lapatinib ditosylate, patients undergo surgical resection of tumor on day 0. Within 30 days of surgical resection of tumor, patients receive lapatinib ditosylate BID for 2 days every 7 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Lapatinib; Drug: Lapatinib Ditosylate; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery

Reference Group (surgery, lapatinib ditosylate)

ACTIVE COMPARATOR

Patients undergo surgery on day 0. Within 30 days of surgical resection of tumor, patients receive lapatinib ditosylate BID for 2 days every 7 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Lapatinib; Drug: Lapatinib Ditosylate; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Group A (lapatinib ditosylate, surgery); Reference Group (surgery, lapatinib ditosylate)

Lapatinib DRUG

Given PO

Also known as: GSK572016, GW 2016, GW 572016, GW-572016, GW2016, GW572016

Group A (lapatinib ditosylate, surgery); Reference Group (surgery, lapatinib ditosylate)

Lapatinib Ditosylate DRUG

Given PO

Also known as: Tykerb

Group A (lapatinib ditosylate, surgery); Reference Group (surgery, lapatinib ditosylate)

Pharmacological Study OTHER

Correlative studies

Group A (lapatinib ditosylate, surgery); Reference Group (surgery, lapatinib ditosylate)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgical resection of tumor

Group A (lapatinib ditosylate, surgery); Reference Group (surgery, lapatinib ditosylate)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically proven World Health Organization (WHO) grade IV glioblastoma/ gliosarcoma or WHO grade III glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, mixed anaplastic oligoastrocytoma, anaplastic ependymoma) which is progressive or recurrent following radiation therapy +/- chemotherapy
• Patients must have measurable, supratentorial contrast-enhancing progressive or recurrent high-grade glioma by magnetic resonance imaging (MRI) imaging within 21 days of starting treatment; patient must be able to tolerate MRIs
• Patients may have an unlimited number of prior therapy regimens
• Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:
• weeks from the completion of radiation
• weeks from a nitrosourea chemotherapy
• weeks from a non-nitrosourea chemotherapy
• weeks from any investigational (not Food and Drug Administration \[FDA\]-approved) agents
• weeks from the last treatment with bevacizumab
• weeks from administration of a non-cytotoxic, FDA-approved agent other than bevacizumab (e.g., hydroxychloroquine, etc.)
• Patients must be undergoing surgery that is clinically indicated as determined by their care providers; patients must be eligible for surgical resection according to the following criteria:
• Expectation that the surgeon is able to resect at least 500 mg of tumor from enhancing tumor and 100 mg from non-enhancing tumor with low risk of inducing neurological injury
• Patient tumor sample must have evidence of EGFR gene amplification by fluorescence in situ hybridization (FISH) using a Clinical Laboratory Improvement Act (CLIA)-certified laboratory assay
• Paraffin embedded tissue must be available from initial surgical resection at diagnosis (prior to any treatment)
• Patients must have a Karnofsky performance status \>= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)

You may not qualify if:

• Patients may not be receiving any other investigational agents
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib are ineligible
• Patients with prior therapy with EGFR inhibitors are ineligible because treatment with EGFR kinase inhibitors or other EGFR-targeted agents has the potential to deplete the tumor of EGFR-amplified or EGFR mutant cell populations and confound the evaluation of lapatinib effects on EGFR phosphorylation; patients with prior EGFRvIII vaccine are eligible if recurrent tumor is positive for EGFR gene amplification
• Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of lapatinib
• Patients must not have evidence of significant hematologic, renal, or hepatic dysfunction
• Patients must not have evidence of significant intracranial hemorrhage
• Patients with uncontrolled intercurrent illness including, but not limited to, hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
• Pregnant women are excluded from this study because lapatinib has potential for teratogenic or abortifacients effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lapatinib, breastfeeding should be discontinued if the mother is treated with lapatinib
• Human immunodeficiency virus (HIV)-positive patients on strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers or inhibitors are ineligible
• Patients who have acute or currently active/requiring anti-viral therapy hepatic or biliary disease are ineligible (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases from the primary brain tumor, or stable chronic liver disease per investigator assessment)
• Patients receiving P-glycoprotein (P-gp) inhibitors are ineligible
• Patients who are receiving a drug that has a risk of QTc prolongation if QTc is \>= 460 msec. are ineligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (12)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Astrocytoma; Ependymoma; Oligodendroglioma; Gliosarcoma; Glioma; Brain Neoplasms; Glioblastoma

Interventions

Lapatinib; N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl-6-(5-((methylsulfonyl)ethyl)aminomethyl)-2-furyl)-4-quinazolinamine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Timothy F Cloughesy

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2014
• First Posted: April 2, 2014
• Study Start: November 7, 2016
• Primary Completion: October 19, 2021
• Study Completion: October 30, 2024
• Last Updated: November 6, 2024

Record last verified: 2024-11

Locations

US (12)