Lapatinib in Treating Patients With Persistent or Recurrent Ovarian Epithelial or Peritoneal Cancer

Study Overview
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Brief Summary
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Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II trial is studying how well lapatinib works in treating patients with persistent or recurrent ovarian epithelial or peritoneal cancer.

Detailed Description
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OBJECTIVES: Primary I. Determine 6-month progression-free survival of patients with persistent or recurrent ovarian epithelial or primary peritoneal cancer treated with lapatinib. II. Determine the nature and degree of toxicity of this drug in these patients. Secondary I. Determine the clinical response rate (partial and complete response) in patients treated with this drug. II. Determine the duration of progression-free and overall survival of patients treated with this drug. III. Determine the impact of prognostic variables, including platinum sensitivity, performance status, and cellular histology (clear cell or mucinous type), on patients treated with this drug. IV. Correlate tumor levels of expression of epidermal growth factor receptors (EGFR), phosphorylated EGFR, HER2/neu, and Ki-67, as determined by immunohistochemistry, with clinical response in patients treated with this drug. V. Correlate EGFR mutations in tumor DNA with clinical response 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. After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 22-60 patients will be accrued for this study within 12-26 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 Epithelial Ovarian or Primary Peritoneal Carcinoma

Conditions
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Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer

Intervention / Treatment
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* Drug: lapatinib ditosylate
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed persistent or recurrent ovarian epithelial or primary peritoneal cancer Measurable disease At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan Presence of ≥ 1 target lesion Tumors within a previously irradiated field are not considered target lesions unless evidence of progression is documented or proven by biopsy 3 months after completion of radiotherapy Disease progression during OR persistent disease after 1 prior platinum-based chemotherapy regimen* for primary disease containing carboplatin, cisplatin, or another organoplatinum compound Initial treatment may have included high-dose therapy, consolidation therapy, or extended therapy administered after surgical or non-surgical assessment Treatment-free interval after platinum-based chemotherapy < 12 months Tumor accessible by guided core needle or fine needle biopsy Ineligible for any higher priority Gynecologic Oncology Group (GOG) protocols (i.e., any active phase III protocol for the same patient population) Performance status - GOG 0-2 (patients who have received 1 prior treatment regimen) Performance status - GOG 0-1 (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) Serum Glutamate Oxaloacetate Transaminase (SGOT) ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Creatinine ≤ 1.5 times ULN Ejection fraction normal by echocardiogram or MUGA No GI 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 disease or ulcerative colitis) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for ≥ 1 month after completion of study treatment No active infection requiring antibiotics No sensory or motor neuropathy > grade 1 No other invasive malignancy within the past 5 years except nonmelanoma skin cancer No history of allergic reaction attributed to compounds of similar chemical or biological composition to lapatinib At least 4 weeks since prior immunologic agents for the malignancy No prior trastuzumab (Herceptin®)or cetuximab See Disease Characteristics Recovered from prior chemotherapy At least 6 weeks since prior nitrosoureas or mitomycin for the malignancy No prior non-cytotoxic chemotherapy for recurrent or persistent disease At least 2 weeks since prior and no concurrent dexamethasone or dexamethasone equivalent dose > 1.5 mg/day At least 1 week since prior hormonal therapy for the malignancy Concurrent hormone replacement therapy allowed See Disease Characteristics Recovered from prior radiotherapy No prior radiotherapy to > 25% of marrow-bearing areas See Disease Characteristics Recovered from prior surgery No prior surgical procedure affecting gastrointestinal (GI) absorption At least 4 weeks since other prior therapy for the malignancy At least 6 months since prior and no concurrent amiodarone At least 1 week since other prior and no concurrent CYP3A4 inhibitors At least 2 weeks since prior and no concurrent CYP3A4 inducers At least 1 week since prior and no concurrent H2 inhibitors or proton pump inhibitors Concurrent antacids allowed provided they are not administered within 1 hour before and 1 hour after study drug administration No prior cancer treatment that would preclude study treatment No prior lapatinib No other prior target-specific therapy directed to the HER family (e.g., gefitinib or erlotinib) No concurrent herbal medications 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>* Given orally<br>* Other names: Tykerb;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) > 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 measurable disease every other cycle for the first 6 months | 
| Frequency and Severity of Adverse Effects as Assessed by Common Toxicity Criteria for Adverse Events (CTCAE) v3.0 |  | Assessed every cycle while on treatment, 30 days after the last cycle of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response | RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate. | Baseline, every other cycle for 6 months and then every 6 months 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 for 6 months and then every 6 months for up to 5 years. | 
| Overall Survival | The observed length of life from entry into the study to death or the date of last contact. | From entry into the study to death or the date of last contact, assessed up to 5 years | 
| Prognostic Variable: Platinum Sensitivity | Patients who had disease progression within 6 months of ending their last regimen of platinum therapy were considered platinum resistant. Patients who had disease progression between 6 and 12 months of ending their last platinum regimen were considered platinum sensitive. Patients who had disease progression beyond12 months of ending their last platinum regimen were also considered platinum sensitive. | Baseline | 
| Prognostic Variables: 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 Performance Status 2 = Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours. | Baseline | 
| Prognostic Variable: Cellular Histology | Number of patients with Clear Cell Carcinoma or Mucinous Carcinoma | Baseline |