Clinical trial NCT00095563 (phase 2, status: completed)
Conditions: 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
ICD codes: C22.0, C22.1, C4A.9, C7B.1, D09.9, C4A.0, C4A.31, C07, C08.0, C08.1, C73, C75.0, C75.1, C75.3
Drugs: lapatinib ditosylate
SMILES: CS(=O)(=O)CCNCC1=CC=C(O1)C1=CC2=C(C=C1)N=CN=C2NC1=CC(Cl)=C(OCC2=CC(F)=CC=C2)C=C1
Eligibility criteria:

        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