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

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Primary Peritoneal Cavity Cancer

Recurrent Ovarian Epithelial Cancer

Treatments

Drug: lapatinib ditosylate

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00113373

CDR0000429548

U10CA027469 (U.S. NIH Grant/Contract)

NCI-2012-02654 (Registry Identifier)

GOG-0170G (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

28 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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