Lapatinib in Treating Patients With Recurrent or Persistent Endometrial Cancer

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Recurrent Endometrial Carcinoma

Treatments

Drug: lapatinib ditosylate

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00096447

U10CA027469 (U.S. NIH Grant/Contract)

CDR0000393398 (Registry Identifier)

NCI-2012-02631

GOG-0229D

Details and patient eligibility

About

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

Full description

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.

Enrollment

31 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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