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
Overview
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Objective Response Rates (Partial and Complete Responses)
Overview
Brief Summary
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
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
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- 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
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
Arms & Interventions
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.
Intervention: lapatinib ditosylate (Drug)
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.
Intervention: laboratory biomarker analysis (Other)
Outcomes
Primary Outcomes
Objective Response Rates (Partial and Complete Responses)
Time Frame: Up to 5 years
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;
Secondary Outcomes
- Most Frequent Adverse Events of Grade 1-2 by CTCAE Grading(Up to 5 years)
- 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(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)(From the date of study enrolment to death or last contact, assessed up to 5 years)