Lapatinib and Radiation for Stage III-IV Head and Neck Cancer Patients Who Cannot Tolerate Concurrent Chemotherapy

NCT00490061 | Terminated Phase 2 Results DMC

• 4 other identifiers: ENT002097864LAP #1098558857
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 5

Brief Summary

We propose to combine lapatinib with RT alone in patients with locally advanced head and neck cancer who cannot tolerate chemotherapy. The main objective of the study is to determine the efficacy of combining concurrent radiation and lapatinib in terms of time-to-progression (TTP) in this group of patients. In addition, we will determine the 2-year locoregional control rate (LRC), progression-free survival (PFS) and overall survival (OS) in these patients. We will also evaluate the profile and frequency of late toxicity, specifically mucosal and dermatologic toxicity, of the combination of lapatinib and RT in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Conditions

Head and Neck Cancer; Carcinoma, Squamous Cell; Head and Neck Cancers

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  To determine the efficacy of combining lapatinib and radiotherapy in terms of Progression-free survival (PFS) in patients with locally advanced HNSCC who cannot tolerate concurrent chemoradiotherapy. Progression-free survival is defined is the time from starting treatment to the time of first documented tumor progression or death due to any cause, which ever occurs first. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST V1.0) as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  2 year PFS: PFS at 2 yrs after study enrollment

Secondary Outcomes (1)

• Overall Survival.

  Two years survival rate after study enrollment

Study Arms (1)

Radiotherapy and Lapatinib with DCE-MRI

EXPERIMENTAL

DCE-MRI will precede radiotherpy before and after Lapatinib loading. 1500mg/d once daily oral Lapatinib will be administration for seven days prior to and throughout radiotherapy. Radiotherapy will be delivered as Intensity Modulated Radio Therapy (IMRT) using a G.E. Healthcare 1.5T MR, systems revision 12.0 M5 for a total dose of 70Gy delivered in 2-2.12 Gy/ fraction over the course of 6.5-7 weeks.

Drug: Lapatinib; Procedure: Radiotherapy (radiation); Device: G.E. Healthcare 1.5T MR, systems revision 12.0 M5; Device: DCE-MRI

Interventions

Lapatinib DRUG

1500 mg po daily orally

Also known as: Tykerb/Tyverb, GlaxoSmithKline

Radiotherapy and Lapatinib with DCE-MRI

Radiotherapy (radiation) PROCEDURE

Standard of Care

Also known as: IMRT - Intensity Modulated Radiotherapy

Radiotherapy and Lapatinib with DCE-MRI

G.E. Healthcare 1.5T MR, systems revision 12.0 M5 DEVICE

Standard of Care, used to deliver IMRT

Also known as: G.E. Healthcare MRI Device and Software

Radiotherapy and Lapatinib with DCE-MRI

DCE-MRI DEVICE

A subset of patients received imaging before and after Lapatinib loading, prior to starting radiotherapy.

Also known as: Dynamic contrast-enhanced magnetic resonance imaging

Radiotherapy and Lapatinib with DCE-MRI

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed stage III-IV HNSCC, pathologically confirmed (HNSCC from unknown primary sites are allowed)
• No evidence of distant metastasis
• No prior radiation therapy to the head and neck sites.
• Able to sign a study-specific informed consent form.
• Women of childbearing potential and men with partners capable of producing offspring must be willing to practice acceptable methods of birth control to prevent pregnancy.
• Left ventricular ejection fraction (LVEF) within the institutional normal range as measured by ECHO (If ECHO cannot be performed or if the Investigator feels that it is not conclusive to evaluate LVEF, then a MUGA scan should be performed).
• Having one of the following parameters that would preclude the use of concurrent CRT:
• ECOG PS \> 2.
• Creatinine \> 1.3 or calculate or measure creatinine clearance \< 60 ml/min.
• AST or ALT \> 1.5 times normal limit but \< 3 times normal limit
• Total bilirubin \> 1.5 mg/dL but \< 3mg/dL
• History of hearing loss that would preclude cisplatin chemotherapy. These would include the existing need of a hearing aid or a \>= 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test.
• Pre-existing peripheral neuropathy that would preclude cisplatin chemotherapy
• Refuse or cannot tolerate chemotherapy
• Age 18 years or older

You may not qualify if:

• Known hypersensitivity to lapatinib or any of the excipients of this product (quinazolines).
• Uncontrolled angina, arrhythmia or congestive heart failure at the time of HNSCC diagnosis and treatment.
• History of myocardial infarction \< 6 months from study entry.
• Treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment.
• Prior treatment with EGFR or Her2/Neu directed therapies.
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with Lapatinib.
• Absolute neutrophil count \< 1500/uL

Sponsors & Collaborators

• Quynh-Thu Le: lead
• GlaxoSmithKline: collaborator

Study Sites (5)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

University of Florida Shands Cancer Center

Gainsville, Florida, 32610, United States

Location

Beth Israel

New York, New York, 10003, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

University of Wisconsin Cancer Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell

Interventions

Lapatinib; halofantrine; Radiotherapy; Radiation; Dynamic Contrast Enhanced Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Therapeutics; Physical Phenomena; Magnetic Resonance Imaging; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Limitations and Caveats

Due to low accrual, this study was terminated prior to reaching 60 subjects.

Results Point of Contact

• Title: Quynh Le
• Organization: Stanford University

qle@stanford.edu

650-498-5032

Study Officials

• Quynh-Thu Le

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor Radiation Oncology

Study Record Dates

• First Submitted: June 20, 2007
• First Posted: June 22, 2007
• Study Start: July 1, 2007
• Primary Completion: January 1, 2013
• Study Completion: June 1, 2016
• Last Updated: March 6, 2017
• Results First Posted: March 6, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)