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