Lapatinib and Topotecan in Treating Patients With Ovarian Epithelial Cancer or Primary Peritoneal Cancer That Did Not Respond to Cisplatin or Carboplatin
Condition: Ovarian Cancer; Peritoneal Cavity Cancer
Intervention: Lapatinib; Topotecan
Intervention description: 1250 mg orally days 1 -28.; 3.2 mg/m2 IV over 30 min in 100mL D5W (5% dextrose in water) or 0.9% NS at days 1, 8 & 15.
Intervention MeSH terms: Topotecan; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent ovarian epithelial cancer; peritoneal cavity cancer

Summary:

      RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Drugs used in chemotherapy, such as topotecan, work in different ways
      to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Giving lapatinib together with topotecan may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving lapatinib together with topotecan
      works in treating patients with ovarian epithelial cancer or primary peritoneal cancer that
      did not respond to cisplatin or carboplatin.
    

Eligibility 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