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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Quynh-Thu Le, Stanford University
ClinicalTrials.gov Identifier:
NCT00490061
First received: June 20, 2007
Last updated: January 22, 2013
Last verified: January 2013
  Purpose

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).


Condition Intervention Phase
Head and Neck Cancer
Carcinoma, Squamous Cell
Head and Neck Cancers
Drug: Lapatinib
Procedure: Radiotherapy
Device: G.E. Healthcare 1.5T MR, systems revision 12.0 M5
Procedure: Pet/CT
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Institutional Phase II Study of Radiation and GW572016 (Lapatinib) for Patients With Stage III-IV Head and Neck Cancer Who Cannot Tolerate Concurrent Chemoradiotherapy.

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Efficacy of combining lapatinib and radiotherapy in terms of time to progression (TTP) in patients with locally advanced HNSCC who cannot tolerate concurrent chemoradiotherapy [ Time Frame: Two years after completion of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 2-year locoregional control, progression free survival and over all survival rates in these patients [ Time Frame: Two years after completion of study ] [ Designated as safety issue: No ]
  • Rate and pattern of late-treatment related toxicity in these patients [ Time Frame: Two years after completion of study ( ] [ Designated as safety issue: Yes ]
  • Role of DCE MRI in predicting treatment outcomes in treated patients Outcome Time Frame: [ Time Frame: Two years after completion of study ( ] [ Designated as safety issue: No ]
  • Changes in the expression of relevant tumoral and circulating biomarkers [ Time Frame: After completion of treatment (2014) ] [ Designated as safety issue: No ]
  • Change in quality of life status relative to baseline [ Time Frame: After completion of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: July 2007
Estimated Study Completion Date: July 2025
Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lapatinib
1500mg/d once daily oral lapatinib administration
Drug: Lapatinib
1500 mg po daily orally
Other Names:
  • Tykerb/Tyverb
  • GlaxoSmithKline
Procedure: Radiotherapy
Standard of Care
Other Name: IMRT - Intensity Modulated Radio Therapy
Device: G.E. Healthcare 1.5T MR, systems revision 12.0 M5
Standard of Care
Other Name: G.E. Healthcare MRI Device and Software
Procedure: Pet/CT
Standard of Care
Other Name: Positron emission tomography - computed tomography

Detailed Description:

There is substantial data to suggest that EGFR and Her-2/neu expressions are important predictors for prognosis in HNSCC. EGFR blockade with a monoclonal antibody in conjunction with radiotherapy has been shown to improve survival over radiotherapy alone in patients with locally advanced HNSCC. Dual inhibition of EGFR and ErbB2 tyrosine kinases results in greater inhibitory effect of the downstream signaling pathways in cancer cells than inhibition of either receptor alone. Phase I studies in HNSCC suggested that the drug is well tolerated when delivered either alone or concurrently with cisplatin based chemoradiotherapy in HNSCC.

We propose to combine lapatinib with RT alone in patients with locally advanced HNSCC 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 HNSCC.

  Eligibility

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

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  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: NCT00490061

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, Florida
Univerisy of Florida Shands Cancer Center
Gainsville, Florida, United States, 32610
United States, New York
Beth Israel
New York, New York, United States, 10003
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Wisconsin
University of Wisconsin Cancer Center
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Quynh-Thu Le
GlaxoSmithKline
Investigators
Principal Investigator: Quynh-Thu Le Stanford University
  More Information

No publications provided

Responsible Party: Quynh-Thu Le, Professor Radiation Oncology, Stanford University
ClinicalTrials.gov Identifier: NCT00490061     History of Changes
Other Study ID Numbers: ENT0020, 97864, LAP #109855, 8857
Study First Received: June 20, 2007
Last Updated: January 22, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Lapatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014