Lapatinib and Radiation for Stage III-IV Head and Neck Cancer Patients Who Cannot Tolerate Concurrent Chemotherapy
Study Details
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Radiotherapy and Lapatinib with DCE-MRI 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
1500 mg po daily orally
Other Names:
Procedure: Radiotherapy (radiation)
Standard of Care
Other Names:
Device: G.E. Healthcare 1.5T MR, systems revision 12.0 M5
Standard of Care, used to deliver IMRT
Other Names:
Device: DCE-MRI
A subset of patients received imaging before and after Lapatinib loading, prior to starting radiotherapy.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival [2 year PFS: PFS at 2 yrs after study enrollment]
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. [Two years survival rate after study enrollment]
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.
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford University School of Medicine | Stanford | California | United States | 94305 |
| 2 | University of Florida Shands Cancer Center | Gainsville | Florida | United States | 32610 |
| 3 | Beth Israel | New York | New York | United States | 10003 |
| 4 | Duke University | Durham | North Carolina | United States | 27710 |
| 5 | 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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ENT0020
- 97864
- LAP #109855
- 8857
Study Results
Participant Flow
| Recruitment Details | Recruitment took place in a radiation oncology clinic, in a private room. The recruitment period spanned from 7/26/2007-11/18/2011. |
|---|---|
| Pre-assignment Detail | # of subjects were screened. |
| Arm/Group Title | Radiotherapy (Radiation) and Lapatinib |
|---|---|
| Arm/Group Description | Lapatinib, 1500mg once daily, was administered for 7 days prior to, and for the duration of Intensity Modulated Radio Therapy (IMRT), delivered by 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. |
| Period Title: Overall Study | |
| STARTED | 17 |
| COMPLETED | 16 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Radiotherapy (Radiation) and Lapatinib |
|---|---|
| Arm/Group Description | 1500mg/d once daily oral lapatinib administration plus Intensity Modulated Radio Therapy (IMRT) delivered by 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. Lapatinib: 1500 mg po daily orally Radiotherapy (radiation): Standard of Care G.E. Healthcare 1.5T MR, systems revision 12.0 M5: Standard of Care, used to deliver IMRT PET/CT: A subset of patients received imaging before and after treatment. |
| Overall Participants | 16 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
3
18.8%
|
| >=65 years |
13
81.3%
|
| Gender (Count of Participants) | |
| Female |
5
31.3%
|
| Male |
11
68.8%
|
Outcome Measures
| Title | Progression Free Survival |
|---|---|
| Description | 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. |
| Time Frame | 2 year PFS: PFS at 2 yrs after study enrollment |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants. |
| Arm/Group Title | Radiotherapy (Radiation) and Lapatinib |
|---|---|
| Arm/Group Description | Lapatinib, 1500mg once daily, was administered for 7 days prior to, and for the duration of Intensity Modulated Radio Therapy (IMRT), delivered by 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. |
| Measure Participants | 16 |
| Number (95% Confidence Interval) [percentage of participants] |
56.2
351.3%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants. |
| Arm/Group Title | Radiotherapy (Radiation) and Lapatinib |
|---|---|
| Arm/Group Description | Lapatinib, 1500mg once daily, was administered for 7 days prior to, and for the duration of Intensity Modulated Radio Therapy (IMRT), delivered by 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. |
| Measure Participants | 16 |
| Number [percentage of participants] |
62.5
390.6%
|
Adverse Events
| Time Frame | 2 years | |
|---|---|---|
| Adverse Event Reporting Description | acute and late AE assessed at follow up appointments | |
| Arm/Group Title | Radiotherapy (Radiation) and Lapatinib | |
| Arm/Group Description | Lapatinib, 1500mg once daily, was administered for 7 days prior to, and for the duration of Intensity Modulated Radio Therapy (IMRT), delivered by 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. | |
All Cause Mortality |
||
| Radiotherapy (Radiation) and Lapatinib | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Radiotherapy (Radiation) and Lapatinib | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/16 (37.5%) | |
| Blood and lymphatic system disorders | ||
| Hemolysis | 1/16 (6.3%) | 1 |
| Immune system disorders | ||
| Lymphopenia | 1/16 (6.3%) | 1 |
| Investigations | ||
| ALT Increased | 1/16 (6.3%) | 1 |
| Metabolism and nutrition disorders | ||
| Hyponatermia | 1/16 (6.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Edema, larynx | 1/16 (6.3%) | 1 |
| Vascular disorders | ||
| Thrombosis/Thrombus/Embolism | 1/16 (6.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Radiotherapy (Radiation) and Lapatinib | ||
| Affected / at Risk (%) | # Events | |
| Total | 8/16 (50%) | |
| Gastrointestinal disorders | ||
| diarrhea | 1/16 (6.3%) | 1 |
| Investigations | ||
| Elevated ALT | 2/16 (12.5%) | 2 |
| Elevated AST | 3/16 (18.8%) | 3 |
| Elevated ALK | 2/16 (12.5%) | 2 |
| Metabolism and nutrition disorders | ||
| Dehydration | 1/16 (6.3%) | 1 |
| Hyponatremia | 1/16 (6.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Aspiration pneumonia | 1/16 (6.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Quynh Le |
|---|---|
| Organization | Stanford University |
| Phone | 650-498-5032 ext 6506370734 |
| qle@stanford.edu |
- ENT0020
- 97864
- LAP #109855
- 8857