Lapatinib in Treating Patients With Recurrent or Persistent Endometrial Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well lapatinib works in treating patients with recurrent or persistent endometrial cancer. Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the 6-month progression-free survival of patients with recurrent or persistent endometrial carcinoma treated with lapatinib. II. Determine the nature and degree of toxicity of this drug in these patients. SECONDARY OBJECTIVES: I. Determine the objective response rate in patients treated with this drug. II. Determine the duration of progression-free survival and overall survival in patients treated with this drug. III. Determine the effects of prognostic factors, such as initial performance status and tumor grade, in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 22-82 patients will be accrued for this study within 30-67 months.

Official Title
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A Phase II Evaluation Of Lapatinib (GW572016) (NCI-Supplied Agent, NSC #727989) In The Treatment Of Persistent Or Recurrent Endometrial Carcinoma

Conditions
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Recurrent Endometrial Carcinoma

Intervention / Treatment
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* Drug: lapatinib ditosylate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed endometrial carcinoma Recurrent or persistent disease Histologic confirmation of the original primary tumor is required Refractory to curative therapy or standard treatments Measurable disease At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques, including palpation, plain x-ray, CT scan, or MRI OR ≥ 10 mm by spiral CT scan Must have at least 1 target lesion Tumors within a previously irradiated field are considered non-target lesions Disease in an irradiated field as the only site of measurable disease is considered a target lesion provided there has been clear progression of the lesion since the completion of prior radiotherapy Must have received 1 prior chemotherapy regimen for endometrial carcinoma Initial therapy may have included high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment No more than 1 additional prior cytotoxic regimen for recurrent or persistent disease Tumor accessible to guided core needle or fine needle biopsy Ineligible for a higher priority GOG protocol (e.g., any active GOG phase III protocol for the same patient population) Performance status - GOG 0-2 (for patients who have received 1 prior treatment regimen) Performance status - GOG 0-1 (for patients who have received 2 prior treatment regimens) Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) SGOT ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Creatinine ≤ 1.5 times ULN Cardiac ejection fraction normal by echocardiogram or MUGA No gastrointestinal (GI) tract disease resulting in an inability to take oral medication No malabsorption syndrome No requirement for IV alimentation No uncontrolled inflammatory GI disease (e.g., Crohn's or ulcerative colitis) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection requiring antibiotics No sensory or motor neuropathy > grade 1 No history of allergic reaction attributed to compounds of similar chemical or biological composition to lapatinib No other invasive malignancy within the past 5 years except nonmelanoma skin cancer At least 4 weeks since prior immunologic agents for the malignant tumor No prior trastuzumab (Herceptin^®) or any target-specific therapy directed to the HER family (e.g., gefitinib, erlotinib, or cetuximab) At least 6 weeks since prior nitrosoureas or mitomycin for the malignant tumor and recovered No prior non-cytotoxic chemotherapy for recurrent or persistent disease At least 1 week since prior hormonal therapy for the malignant tumor Concurrent hormone replacement therapy allowed Recovered from prior radiotherapy Recovered from prior surgery No prior surgery affecting absorption At least 4 weeks since other prior therapy for the malignant tumor No prior lapatinib No prior anticancer treatment that would preclude study treatment Concurrent oral anticoagulants (e.g., warfarin) allowed provided there is increased monitoring of INR No concurrent CYP3A4 inducers or inhibitors No concurrent combination antiretroviral therapy for HIV-positive patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (lapatinib ditosylate)<br>Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: lapatinib ditosylate<br> <br> * Other names: Tykerb;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Progression-free Survival > 6 Months | Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. | For those patients whose disease can be evaluated by physical examination, progression was assessed prior to each 28-day cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle, for up to 5 years. | 
| Frequency and Severity of Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 | The frequency and severity of all toxicities are tabulated. | Every cycle during treatment and 30 days after the last cycle of therapy. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Tumor Response | Complete and Partial Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. 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; Overall Response (OR) = CR + PR. | For those patients whose disease can be evaluated by physical examination, response was assessed prior to each 28-day cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle, for up to 5 years. | 
| Duration of Progression-free Survival | Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. | Every other cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years. | 
| Overall Survival | The observed length of life from entry into the study to death or the date of last contact. | From study entry to death or last contact, up to 5 years. | 
| Prognostic Factors (Performance Status) | Performance status 0 = Fully active, able to carry on all pre-disease performance without restriction. Performance status 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature, e.g., light housework, office work. | Baseline | 
| Prognostic Factor (Histologic Grade) | G1 - Highly differentiated adenomatous carcinoma. G2 - Differentiated adenomatous carcinoma with partly solid areas. G3 - Predominantly solid or entirely undifferentiated carcinoma. Not graded - tumor grade not reported. | Baseline |