Lapatinib in Treating Patients With Recurrent and/or Metastatic Adenoid Cystic Cancer or Other Salivary Gland Cancers

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of lapatinib in treating patients who have recurrent and/or metastatic adenoid cystic cancer or other salivary gland cancers. Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the antitumor activity of GW572016 in recurrent and/or metastatic adenoid cystic carcinoma of the salivary glands using objective response rates (partial and complete responses). SECONDARY OBJECTIVES: I. To determine the duration of objective response, rate and duration of stable disease, progression-free, median and overall survival rates of GW572016 in recurrent and/or metastatic adenoid cystic carcinoma of the salivary glands. II. To estimate the antitumor activity of GW572016 in other epidermal growth factor receptor (EGFR)- and/or erbB2-overexpressing malignant tumors of the salivary glands using objective response rates (partial and complete responses). III. To document the safety and tolerability of GW572016 in these patient populations TERTIARY OBJECTIVES: I. To investigate if differences in baseline levels of EGFR and/or erbB2 expression, and receptor phosphorylation status in tumor specimens predict outcome to therapy. II. To investigate if the inhibitory effects of GW572016 on EGFR and/or erbB2 pathway activation in tumor specimens correlate with clinical outcome. III. To determine the steady state levels of GW572016 achieved, and their correlation with clinical and laboratory correlative endpoints. OUTLINE: This is a nonrandomized, open-label, multicenter study. Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients are followed for survival

Official Title
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A Phase 2 Study of GW572016 in Recurrent and/or Metastatic Adenoid Cystic Carcinoma, and Other EGFR-and/or erbB2-expressing Malignant Tumors of the Salivary Glands

Conditions
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High-grade Salivary Gland Carcinoma, High-grade Salivary Gland Mucoepidermoid Carcinoma, Low-grade Salivary Gland Carcinoma, Low-grade Salivary Gland Mucoepidermoid Carcinoma, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Salivary Gland Cancer, Salivary Gland Acinic Cell Tumor, Salivary Gland Adenocarcinoma, Salivary Gland Adenoid Cystic Carcinoma, Salivary Gland Malignant Mixed Cell Type Tumor

Intervention / Treatment
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* Drug: lapatinib ditosylate
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically documented or cytologically confirmed adenoid cystic, or other malignant salivary gland carcinomas of major or minor salivary gland origin; all patients must have either EGFR and/or erbB2 expressing tumors (for definitions of EGFR and erbB2 expression to be enrolled in this study; EGFR and erbB2 expression will be determined using archival paraffin samples for all study patients where possible; if these samples are unavailable then patients must undergo a biopsy to determine their EGFR and erbB2 status Patients must have recurrent and/or metastatic disease that is progressive and not amenable to surgery or curative radiotherapy; progressive disease is defined as one of the following occurring within 6 months of study entry: At least a 20% increase in radiologically or clinically measurable disease Appearance of any new lesions or Deterioration in clinical status Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan Patients may have had unlimited prior therapy; however, there must be at least a 4 weeks' interval between any chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy or surgery and study enrollment; exceptions may be made however, for low dose, non-myelosuppressive radiotherapy - please contact the Principal Investigator (Dr. L. Siu) PRIOR to registration if questions arise about the interpretation of this criterion; for patients who received local therapy prior to study entry, there must be either progression of measurable disease documented within the treatment field, or must have measurable disease outside the treatment field prior to study entry Life expectancy of greater than 12 weeks ECOG performance status 0,1, or 2 Leukocytes >= 3,000/uL Absolute neutrophil count >= 1,5000/uL Platelets >= 100,000/uL Total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal Creatinine within normal institutional limits OR Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA scan: Note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution Must be willing and able to undergo tumor biopsy once before and once during investigational therapy; patients must have tumor lesions accessible for biopsy for correlative studies; the decision regarding the safety of doing a biopsy will be made by an interventional radiologist rather than the investigator and must be documented in writing; in cases where there is a medical contraindication to tumor biopsy, exception may be granted only upon discussion with the principal investigator Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of GW572016 will be determined following review of their use by the principal investigator; a list of medications and substances known or with the potential to interact with CYP450 isoenzymes is provided in: Cytochrome P-450 Enzymes and Drug metabolism; in: Lacy CF, Armstrong LL, Goldman MP, Lance LL eds; Drug Information Handbook 8TH ed. Hudson, OH; LexiComp Inc. 2000: 1364-1371 HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with GW572016; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated Patients requiring oral anticoagulants (coumadin, warfarin) are eligible provided there is increased vigilance with respect to monitoring INR; if medically appropriate and treatment available, the investigator may also consider switching these patients to LMW heparin, where an interaction with GW572016 is not expected Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Able to swallow and retain oral medication; alternately, for patients who require feeding via nasogastric tubes or who cannot swallow whole tablets, study entry is allowed by following instructions on drug administration Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier Patients who have had prior treatment with EGFR or erbB2 targeting therapies Patients may not be receiving any other investigational agents or receiving concurrent anticancer therapy Patients with known brain metastases but have remained stable for at least 3 months since completion of radiotherapy or surgery, have no significant neurological deficits, and are off corticosteroids, may be allowed on study; patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events Patients with a history of other active malignancy in the past 5 years (with the exception of adequately treated cervical carcinoma in situ and non-melanomatous skin cancers) are excluded History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, 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 from this study because GW572016 is member of the 4-anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or abortifacient effects; breastfeeding should be discontinued if the mother is treated with GW572016 HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis) Concomitant requirement for medication classified as CYP3A4 inducer or inhibitor

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (lapatinib ditosylate)<br>Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. | Drug: lapatinib ditosylate<br>* Given orally<br>* Other names: Tykerb;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rates (Partial and Complete Responses) | 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; | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Objective Response |  | From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years | 
| Rate of Stable Disease | Number of patients who had Stable disease for more than or equal to 6 months together in both Adenoid cystic carcinoma (ACC) and non-adenoid cyctic carcinoma (non-ACC) | 6 months | 
| Progression-free Survival (PFS) According to RECIST |  | From the date of study enrolment to disease progression, death or last contact, or last tumor assessment before the start of further anti-tumor therapy, assessed up to 5 years | 
| Overall Survival (OS) | Survival estimates will be computed using the Kaplan-Meier method. | From the date of study enrolment to death or last contact, assessed up to 5 years | 
| Most Frequent Adverse Events of Grade 1-2 by CTCAE Grading | Number of participants that experienced the most frequent adverse events of grade 1-2 by CTCAE grading. | Up to 5 years |