A Phase II Trial of Lapatinib in Combination With Weekly Topotecan in Patients With Platinum-Refractory/Resistant Ovarian and Primary Peritoneal Carcinoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed ovarian epithelial or primary peritoneal carcinoma

- Must have one of the following:

- Measurable disease

- Evaluable disease AND a CA-125 value that has increased ≥ 2 times the nadir
value established after debulking surgery and first-line chemotherapy, confirmed
by a second measurement within the past 21 days

- If a second measurement has not been done, it can be done ≥ 7 days but < 21
days prior to study treatment

- Platinum-refractory and/or -resistant disease after first-line chemotherapy

- Patients retreated with platinum agents (i.e., second relapse) are not eligible

- Patients treated with first-line triplet therapy (e.g., on clinical trial
GOG-182) are eligible

- Must have had debulking surgery

- Tissue blocks from this surgery must be available

- No CNS metastases

PATIENT CHARACTERISTICS:

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Life expectancy ≥ 12 weeks

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST ≤ 3 times ULN (5 times ULN if there is liver involvement)

- Creatinine ≤ 1.5 times ULN

- Hemoglobin ≥ 9.0 g/dL

- No uncontrolled infection

- No New York Heart Association class III or IV heart failure

- Left Ventricular Ejection Fraction (LVEF) ≥ 50% by echocardiogram

- No seizure disorder

- No other prior or concurrent malignancy in the past 5 years except nonmelanoma skin
cancer or carcinoma in situ of the cervix

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior topotecan hydrochloride

- More than 4 weeks since prior surgery or procedure involving the peritoneum or pleura

- CA125 measurements used as basis for enrollment must be made outside of this
4-week window

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
and recovered

- More than 4 weeks since prior immunotherapy

- More than 4 weeks since prior biologic therapy

- More than 4 weeks since prior radiotherapy

- No prior radiotherapy to > 25 % of bone marrow

- No prior therapy with an anti-epidermal growth factor receptor or anti-HER2 tyrosine
kinase inhibitors

- No prior agents targeting topoisomerase I

- No prior or concurrent human anti-mouse antibodies (HAMA) in patients with
non-measurable disease

- At least 14 days since prior and no concurrent herbal or dietary supplements

- Vitamin supplements are allowed unless they include herbal additives

- At least 14 days since prior and no concurrent CYP3A4 inducers, including any of the
following:

- Rifampin

- Rifabutin

- Rifapentine

- Phenytoin

- Carbamazepine

- Phenobarbital

- Efavirenz

- Nevirapine

- Cortisone (> 50 mg)

- Hydrocortisone (> 40 mg)

- Prednisone (> 10 mg)

- Methylprednisolone (> 8 mg)

- Dexamethasone (> 1.5 mg)

- Oral doses of ≤ 1.6 mg of dexamethasone allowed

- Modafinil

- Hypericum perforatum (St. John's wort)

- At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the
following:

- Clarithromycin

- Erythromycin

- Troleandomycin

- Itraconazole

- Ketoconazole

- Fluconazole (> 150 mg daily)

- Voriconazole

- Delaviridine

- Nelfinavir

- Amprenavir

- Ritonavir

- Indinavir

- Saquinavir

- Lopinavir

- Verapamil

- Diltiazem

- Nefazodone

- Fluvoxamine

- Cimetidine

- Aprepitant

- Grapefruit or grapefruit juice

- At least 6 months since prior and no concurrent amiodarone

- No concurrent participation in another study involving a pharmacologic agent (e.g.,
drugs, biologics, immunotherapy, gene therapy) for symptom control or therapeutic
intent