Back to results

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

Primary Purpose

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

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Lapatinib

Radiotherapy (radiation)

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

DCE-MRI

About this trial

This is an interventional treatment trial for Head and Neck Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Stanford University School of Medicine
University of Florida Shands Cancer Center
Beth Israel
Duke University
University of Wisconsin Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Radiotherapy and Lapatinib with DCE-MRI

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall Survival.

Overall survival is the time from starting treatment until death due to any cause. For subjects who do not die, time to death will be censored at the time of last contact.

Full Information

NCT ID

NCT00490061

First Posted

June 20, 2007

Last Updated

January 13, 2017

Sponsor

Quynh-Thu Le

Collaborators

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT00490061

Brief Title

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

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.

Study Type

Interventional

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Terminated

Why Stopped

Poor accrual.

Study Start Date

July 2007 (undefined)

Primary Completion Date

January 2013 (Actual)

Study Completion Date

June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Quynh-Thu Le

Collaborators

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Radiotherapy and Lapatinib with DCE-MRI

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Lapatinib

Other Intervention Name(s)

Tykerb/Tyverb, GlaxoSmithKline

Intervention Description

1500 mg po daily orally

Intervention Type

Procedure

Intervention Name(s)

Radiotherapy (radiation)

Other Intervention Name(s)

IMRT - Intensity Modulated Radiotherapy

Intervention Description

Standard of Care

Intervention Type

Device

Intervention Name(s)

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

Other Intervention Name(s)

G.E. Healthcare MRI Device and Software

Intervention Description

Standard of Care, used to deliver IMRT

Intervention Type

Device

Intervention Name(s)

DCE-MRI

Other Intervention Name(s)

Dynamic contrast-enhanced magnetic resonance imaging

Intervention Description

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

Primary Outcome Measure Information:

Title

Progression Free Survival

Description

Time Frame

2 year PFS: PFS at 2 yrs after study enrollment

Secondary Outcome Measure Information:

Title

Overall Survival.

Description

Overall survival is the time from starting treatment until death due to any cause. For subjects who do not die, time to death will be censored at the time of last contact.

Time Frame

Two years survival rate after study enrollment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Quynh-Thu Le

Organizational Affiliation

Stanford University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Stanford University School of Medicine

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

Facility Name

University of Florida Shands Cancer Center

City

Gainsville

State/Province

Florida

ZIP/Postal Code

32610

Country

United States

Facility Name

Beth Israel

City

New York

State/Province

New York

ZIP/Postal Code

10003

Country

United States

Facility Name

Duke University

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

University of Wisconsin Cancer Center

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53792

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs