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

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: November 5, 2004
Last updated: October 10, 2013
Last verified: October 2013
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.

Condition Intervention Phase
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
Drug: lapatinib ditosylate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response rates (partial and complete responses) according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of objective response [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Rate and duration of stable disease [ Time Frame: From the start of the treatment until the criteria for progression are met, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) according to RECIST [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: From the date of study enrolment to death or last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
    Survival estimates will be computed using the Kaplan-Meier method.

  • Toxicity graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Enrollment: 67
Study Start Date: September 2004
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (lapatinib ditosylate)
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
Given orally
Other Names:
  • GSK572016
  • GW-572016
  • GW2016
  • Lapatinib
  • Tykerb
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:


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).


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


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00095563

Canada, Ontario
Princess Margaret Hospital Phase 2 Consortium
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Lillian Siu Princess Margaret Hospital Phase 2 Consortium
  More Information

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00095563     History of Changes
Other Study ID Numbers: NCI-2012-03089  NCI-2012-03089  6701  PHL-028  6701  N01CM62201  N01CM62203 
Study First Received: November 5, 2004
Last Updated: October 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Salivary Gland Neoplasms
Carcinoma, Acinar Cell
Carcinoma, Adenoid Cystic
Carcinoma, Mucoepidermoid
Head and Neck Neoplasms
Mouth Diseases
Mouth Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Cystic, Mucinous, and Serous
Neoplasms, Glandular and Epithelial
Salivary Gland Diseases
Stomatognathic Diseases
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors processed this record on May 30, 2016