Capecitabine and Lapatinib Ditosylate in Treating Patients With Squamous Cell Cancer of the Head and Neck
Primary Purpose
Head and Neck Cancer, Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Metastatic Squamous Neck Cancer With Occult Primary
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
lapatinib ditosylate
capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Cancer
Eligibility Criteria
Inclusion
- Histologically or cytologically confirmed SCCHN
- All primary sites are eligible excluding nasopharyngeal
- Metastatic disease or locally recurrent disease not felt amenable to curative therapy (as determined by a physician)
- ECOG performance status 0-2
- No prior chemotherapy in the metastatic / locally advanced, recurrent incurable setting; patients may have received prior curative-intention chemotherapy including induction chemotherapy, chemotherapy concurrent with radiation and adjuvant chemotherapy
- No prior capecitabine; patients who have received 5-FU or other fluoropyrimidines in the curative-intention setting will not be excluded, as long as more than 6 mos have elapsed since prior 5-FU exposure
- No previous history of Lapatinib
- Previous use of cetuximab in the curative-intention setting will not result in exclusion, as long as at least four weeks have elapsed since prior C225 exposure
- Patients may have received radiation therapy in the definitive, adjuvant or metastatic setting; radiation therapy must be completed at least 14 days prior to study participation
- ECOG performance status of 0-2 (Karnofsky >= 60%)
- Must have normal organ and marrow function
- Laboratory tests should be completed within 14 days prior to registration
- Left ventricular ejection fraction (LVEF) can be determined by either echocardiography or nuclear scintigraphy and should be obtained within 21 days of enrollment
- Platelets >= 100,000/mm^3
- Total bilirubin =< 2
- Albumin > 2.5
- AST(SGOT)/ALT(SGPT) =< 5.0 X institutional upper limit of normal (for patients with hepatic metastases) =< 3.0 X institutional upper limit of normal (for patients without hepatic metastases)
- GFR > 30 (by standard Cockroft and Gault formula)
- LVEF >= 50%
- Patients may receive anticoagulant medication while on study
- Patients may not receive other antineoplastic therapies such as chemotherapy or radiation treatments while on study; patients may not receive other experimental treatments while on study; patients requiring radiation treatments during protocol-based treatment will be taken off study
- Patients may receive concurrent bisphosphonate therapy as well as hormonal manipulations for appetite while on study
- Patients must neither be pregnant nor expect to become pregnant while on study
- Patients must have the ability to understand and the willingness to sign a written informed consent document
- Adequate swallowing function or gastric-tube for drug administration
- No disability with absorption of internal medications
- Adequate nutritional status: Patients will not be excluded based on previous weight loss but will be required to have adequate nutrition at the time of study entry as measured by serum albumin
- ANC >= 1,500/mm^3
- Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
Exclusion
- Patients who have received prior capecitabine chemotherapy or lapatinib
- Patients with brain metastases may participate if they have undergone appropriate treatment for the lesion(s), are at least two weeks post treatment without evidence for post-treatment progression, have no significant neurologic symptoms, and are no longer on steroids for brain metastases
- Patients with symptoms concerning for CNS metastases should be evaluated with imaging prior to study participation
- Less than 3 weeks elapsed since prior exposure to chemotherapy
- LVEF < 50% or symptomatic congestive heart failure (CHF)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded due to the potential for teratogenic or abortifacient effects of capecitabine and lapatinib; because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued prior to participation of the mother on study
- Other active, invasive malignancy requiring ongoing therapy or expected to require systemic therapy within two years; localized squamous cell carcinoma of the skin, basal-cell carcinoma of the skin, carcinoma in-situ of the cervix, or other malignancies requiring locally ablative therapy only will not result in exclusion
- Have received treatment within the last 30 days prior to study entry with any drug that has not received regulatory approval for an indication at the time of study entry
- Previous CHF or other cardiac conditions shall not result in exclusion if the treating physician does not see contraindication to these medications; if contraindication is controversial, cardiac consultation will be obtained prior to the initiation of therapy
- Anti-cancer therapy (other than the investigational regimen) is prohibited from 3 weeks before the first dose of investigational product through discontinuation unless otherwise noted
- Investigational drugs are not permitted from 3 weeks (21 days) or 5 half-lives, whichever is longer, prior to the first dose and up through 30 days after the last dose of investigational product
- CYP3A4 inducers and inhibitors, antacids, and herbal or dietary supplements
- Concurrent radiation therapy and surgery for SCCHN is prohibited during therapy
Sites / Locations
- Abramson Cancer Center of The University of Pennsylvania
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm I
Arm Description
Patients receive oral lapatinib ditosylate once daily on days 1-21 and oral capecitabine twice daily on days 1-14.
Outcomes
Primary Outcome Measures
Overall Survival
Secondary Outcome Measures
Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Disease Control Rate
Progression-free Survival
Number of Participants With Adverse Events and Serious Adverse Events
ADVERSE EVENTS (AE) AND SERIOUS ADVERSE EVENTS (SAE) Adverse Events (AEs) will use the descriptions and grading scales found in the NCI CTCAE v3.0
Full Information
NCT ID
NCT01044433
First Posted
December 10, 2009
Last Updated
March 6, 2020
Sponsor
Abramson Cancer Center at Penn Medicine
1. Study Identification
Unique Protocol Identification Number
NCT01044433
Brief Title
Capecitabine and Lapatinib Ditosylate in Treating Patients With Squamous Cell Cancer of the Head and Neck
Official Title
A Phase II Study of Capecitabine and Lapatinib in Squamous Cell Carcinoma of the Head and Neck
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
October 2009 (Actual)
Primary Completion Date
September 24, 2015 (Actual)
Study Completion Date
March 3, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Abramson Cancer Center at Penn Medicine
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving capecitabine together with lapatinib ditosylate may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving capecitabine and lapatinib ditosylate together works in treating patients with squamous cell cancer of the head and neck.
Detailed Description
PRIMARY OBJECTIVE:
I. Overall survival (OS) will be the primary endpoint.
SECONDARY OBJECTIVES:
I. Progression free survival (PFS). II. Time to disease progression and sites of progression. III. Response rate. IV. Toxicity of the combination in this population. V. Quality of life.
OUTLINE:
Patients receive oral lapatinib ditosylate once daily on days 1-21 and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for up to 5 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer, Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Salivary Gland Cancer, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Recurrent Verrucous Carcinoma of the Larynx, Recurrent Verrucous Carcinoma of the Oral Cavity, Salivary Gland Squamous Cell Carcinoma, Stage IV Salivary Gland Cancer, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Larynx, Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IV Squamous Cell Carcinoma of the Oropharynx, Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IV Verrucous Carcinoma of the Larynx, Stage IV Verrucous Carcinoma of the Oral Cavity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients receive oral lapatinib ditosylate once daily on days 1-21 and oral capecitabine twice daily on days 1-14.
Intervention Type
Drug
Intervention Name(s)
lapatinib ditosylate
Other Intervention Name(s)
GSK572016, GW-572016, GW2016, lapatinib, Tykerb
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
capecitabine
Other Intervention Name(s)
CAPE, Ro 09-1978/000, Xeloda
Intervention Description
Given orally
Primary Outcome Measure Information:
Title
Overall Survival
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Response Rate
Description
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame
5 years
Title
Disease Control Rate
Time Frame
5 years
Title
Progression-free Survival
Time Frame
5 years
Title
Number of Participants With Adverse Events and Serious Adverse Events
Description
ADVERSE EVENTS (AE) AND SERIOUS ADVERSE EVENTS (SAE) Adverse Events (AEs) will use the descriptions and grading scales found in the NCI CTCAE v3.0
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion
Histologically or cytologically confirmed SCCHN
All primary sites are eligible excluding nasopharyngeal
Metastatic disease or locally recurrent disease not felt amenable to curative therapy (as determined by a physician)
ECOG performance status 0-2
No prior chemotherapy in the metastatic / locally advanced, recurrent incurable setting; patients may have received prior curative-intention chemotherapy including induction chemotherapy, chemotherapy concurrent with radiation and adjuvant chemotherapy
No prior capecitabine; patients who have received 5-FU or other fluoropyrimidines in the curative-intention setting will not be excluded, as long as more than 6 mos have elapsed since prior 5-FU exposure
No previous history of Lapatinib
Previous use of cetuximab in the curative-intention setting will not result in exclusion, as long as at least four weeks have elapsed since prior C225 exposure
Patients may have received radiation therapy in the definitive, adjuvant or metastatic setting; radiation therapy must be completed at least 14 days prior to study participation
ECOG performance status of 0-2 (Karnofsky >= 60%)
Must have normal organ and marrow function
Laboratory tests should be completed within 14 days prior to registration
Left ventricular ejection fraction (LVEF) can be determined by either echocardiography or nuclear scintigraphy and should be obtained within 21 days of enrollment
Platelets >= 100,000/mm^3
Total bilirubin =< 2
Albumin > 2.5
AST(SGOT)/ALT(SGPT) =< 5.0 X institutional upper limit of normal (for patients with hepatic metastases) =< 3.0 X institutional upper limit of normal (for patients without hepatic metastases)
GFR > 30 (by standard Cockroft and Gault formula)
LVEF >= 50%
Patients may receive anticoagulant medication while on study
Patients may not receive other antineoplastic therapies such as chemotherapy or radiation treatments while on study; patients may not receive other experimental treatments while on study; patients requiring radiation treatments during protocol-based treatment will be taken off study
Patients may receive concurrent bisphosphonate therapy as well as hormonal manipulations for appetite while on study
Patients must neither be pregnant nor expect to become pregnant while on study
Patients must have the ability to understand and the willingness to sign a written informed consent document
Adequate swallowing function or gastric-tube for drug administration
No disability with absorption of internal medications
Adequate nutritional status: Patients will not be excluded based on previous weight loss but will be required to have adequate nutrition at the time of study entry as measured by serum albumin
ANC >= 1,500/mm^3
Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
Exclusion
Patients who have received prior capecitabine chemotherapy or lapatinib
Patients with brain metastases may participate if they have undergone appropriate treatment for the lesion(s), are at least two weeks post treatment without evidence for post-treatment progression, have no significant neurologic symptoms, and are no longer on steroids for brain metastases
Patients with symptoms concerning for CNS metastases should be evaluated with imaging prior to study participation
Less than 3 weeks elapsed since prior exposure to chemotherapy
LVEF < 50% or symptomatic congestive heart failure (CHF)
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant women are excluded due to the potential for teratogenic or abortifacient effects of capecitabine and lapatinib; because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued prior to participation of the mother on study
Other active, invasive malignancy requiring ongoing therapy or expected to require systemic therapy within two years; localized squamous cell carcinoma of the skin, basal-cell carcinoma of the skin, carcinoma in-situ of the cervix, or other malignancies requiring locally ablative therapy only will not result in exclusion
Have received treatment within the last 30 days prior to study entry with any drug that has not received regulatory approval for an indication at the time of study entry
Previous CHF or other cardiac conditions shall not result in exclusion if the treating physician does not see contraindication to these medications; if contraindication is controversial, cardiac consultation will be obtained prior to the initiation of therapy
Anti-cancer therapy (other than the investigational regimen) is prohibited from 3 weeks before the first dose of investigational product through discontinuation unless otherwise noted
Investigational drugs are not permitted from 3 weeks (21 days) or 5 half-lives, whichever is longer, prior to the first dose and up through 30 days after the last dose of investigational product
CYP3A4 inducers and inhibitors, antacids, and herbal or dietary supplements
Concurrent radiation therapy and surgery for SCCHN is prohibited during therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Corey Langer
Organizational Affiliation
Abramson Cancer Center at Penn Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Abramson Cancer Center of The University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Capecitabine and Lapatinib Ditosylate in Treating Patients With Squamous Cell Cancer of the Head and Neck
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