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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

Phase 2
18 Years
Not Enrolling
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

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Trial Information

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


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


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


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

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

- 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

- Concomitant requirement for medication classified as CYP3A4 inducer or inhibitor

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rates (partial and complete responses) according to Response Evaluation Criteria in Solid Tumors (RECIST)

Outcome Time Frame:

Up to 5 years

Safety Issue:


Principal Investigator

Lillian Siu

Investigator Role:

Principal Investigator

Investigator Affiliation:

Princess Margaret Hospital Phase 2 Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

September 2004

Completion Date:

Related Keywords:

  • 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
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Carcinoma, Adenoid Cystic
  • Salivary Gland Neoplasms
  • Carcinoma, Acinar Cell
  • Carcinoma, Mucoepidermoid