Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	PMH-PHL-028 NCI-6701, 6701, NCT00095563

Objectives

Primary

1. Determine the antitumor activity of lapatinib, in terms of objective response rate (partial response [PR] and complete response [CR]), in patients with recurrent and/or metastatic adenoid cystic carcinoma of the salivary gland.

Secondary

1. Determine the duration of objective response in patients treated with this drug.
2. Determine the rate and duration of stable disease in patients treated with this drug.
3. Determine progression-free, median, and overall survival of patients treated with this drug.
4. Determine the antitumor activity of this drug, in terms of objective response rate (PR and CR), in patients with other epidermal growth factor receptor- and/or ERBB2-overexpressing malignant tumors of the salivary gland.
5. Determine the safety and tolerability of this drug in these patient populations.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed adenoid cystic or other malignant salivary gland carcinoma of major or minor salivary gland origin, meeting 1 of the following criteria:
  • Epidermal growth factor receptor (EGFR) expressing tumors
  • ERBB2 expressing tumors



• Recurrent and/or metastatic disease



• Progressive disease as defined by 1 of the following criteria occurring within in the past 6 months:
  • At least a 20% increase in radiologically or clinically measurable disease
  • Appearance of any new lesions
  • Deterioration in clinical status



• Not amenable to surgery or curative radiotherapy



• Measurable disease
  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
  • Lesion must be outside of field of prior local therapy OR disease has progressed within the treatment field



• No symptomatic brain metastases
  • Patients with known brain metastases that have been stable ≥ 3 months since completion of radiotherapy or surgery and who have no significant neurological deficits and are off corticosteroids are eligible



• Tumor lesions accessible for biopsy
  • In the event that tumor biopsy is medically contraindicated exceptions may be granted by the Principal Investigator only

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy, except low-dose, non-myelosuppressive radiotherapy

Surgery

• No prior gastrointestinal surgical procedures affecting absorption
• At least 4 weeks since prior surgery

Other

• Recovered from all prior therapy
• No prior EGFR or ERBB2-targeting therapies
• At least 7 days since prior and no concurrent CYP3A4 inhibitors
• At least 14 days since prior and no concurrent CYP3A4 inducers
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapy

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 12 weeks

Hematopoietic

• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal

Renal

• Creatinine normal

  OR

• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• Cardiac ejection fraction normal by echocardiogram or MUGA
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal

• Able to swallow and retain oral medication
• No gastrointestinal disease resulting in an inability to take oral medication
• No malabsorption syndrome
• No requirement for IV alimentation
• No uncontrolled inflammatory gastrointestinal disease (e.g., Crohn's disease or ulcerative colitis)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Willing and able to undergo tumor biopsy (unless medically contraindicated)
• No other active malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to lapatinib
• No other uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance

Expected Enrollment

A total of 12-67 patients (12-37 patients with adenoid cystic carcinoma [ACC] of the salivary gland and a maximum of 30 patients with epidermal growth factor receptor- or ERBB2-expressing non-ACC of the salivary gland) will be accrued for this study within 18 months.

Outcomes

Objective response rate (complete response and partial response)

Objective response duration
Stable disease rate
Stable disease duration
Progression-free survival at 6 months and 1 year
Overall survival at 6 months and 1 year
Median survival
Safety and tolerability

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.

Agulnik M, Cohen EW, Cohen RB, et al.: Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and/or erbB2 expressing adenoid cystic carcinoma and non adenoid cystic carcinoma malignant tumors of the salivary glands. J Clin Oncol 25 (25): 3978-84, 2007.[PUBMED Abstract]

Elser C, Tsao M, Pond G, et al.: Fluororescence in situ hybridization (FISH) gene amplification analysis of EGFR and HER2 in patients with malignant salivary gland tumors (MSGT) treated with lapatinib. [Abstract] American Association for Cancer Research: Molecular Targets and Cancer Therapeutics, October 22-26, 2007, San Francisco, CA A-C41, 2007.

Trial Contact Information

Trial Lead Organizations

Princess Margaret Hospital

Lillian Siu, MD, FRCPC, Principal investigator		Ph: 416-946-2911

Registry Information
Official Title		A Phase II Study of Lapatinib in Recurrent and/or Metastatic Adenoid Cystic Carcinoma and Other Epidermal Growth Factor Receptor- and/or erbB2-Expressing Malignant Tumors of the Salivary Glands
Trial Start Date		2004-11-05
Trial Completion Date		2009-06-11
Registered in ClinicalTrials.gov		NCT00095563
Date Submitted to PDQ		2004-10-04
Information Last Verified		2006-01-23
NCI Grant/Contract Number		CM62203, CM62201

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