Lapatinib and Topotecan in Treating Patients With Ovarian Epithelial Cancer or Primary Peritoneal Cancer That Did Not Respond to Cisplatin or Carboplatin

NCT ID: NCT00436644

Last Updated: 2014-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2012-11-30

Brief 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.

Detailed Description

OBJECTIVES:

Primary

• Determine the efficacy of lapatinib ditosylate and topotecan hydrochloride, in terms of response, in patients with platinum-resistant or refractory ovarian epithelial or primary peritoneal cavity carcinoma.

Secondary

• Determine the overall survival time in patients treated with this regimen.
• Determine the time to progression in patients treated with this regimen.
• Assess the toxicity profile of this regimen in these patients.

Translational

• Determine the expression patterns of epidermal growth factor receptor, HER2/neu, hypoxia-induced factor 1 alpha, CD31, breast cancer resistance protein, and topoisomerase I by immunohistochemistry using tumor tissue from primary debulking surgery.
• Determine the feasibility of monitoring circulating tumor cells with specific biological markers to determine or follow response in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral lapatinib ditosylate once daily on days 1-28 and topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and on day 8 of course 1 (immediately after the topotecan infusion) and are evaluated for pharmacological studies. Tumor tissue samples obtained at debulking surgery are examined by immunohistochemistry for epidermal growth factor receptor, HER1, ErbB1, HER2/neu, ErbB2, hypoxia-induced factor 1 alpha, CD31, platelet endothelial cell adhesion molecule 1, topoisomerase I, and breast cancer resistance protein.

After the completion of study treatment, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study.

Conditions

Ovarian Cancer; Peritoneal Cavity Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lapatinib + Topotecan

Assess biological effects of topotecan and lapatinib in patients with epithelial ovarian cancer and primary peritoneal carcinoma.

Group Type: EXPERIMENTAL

Lapatinib

Intervention Type: DRUG

1250 mg orally days 1 -28.

Topotecan

Intervention Type: DRUG

3.2 mg/m2 IV over 30 min in 100mL D5W (5% dextrose in water) or 0.9% NS at days 1, 8 \& 15.

Interventions

Lapatinib

1250 mg orally days 1 -28.

Intervention Type: DRUG

Topotecan

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 Type: DRUG

Other Intervention Names

Tykerb; Hycamptin

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Mayo Clinic Cancer Center

Principal Investigators

Paul Haluska, MD, PhD

Role: STUDY_CHAIR

Mayo Clinic

John K. Camoriano, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Candido E. Rivera, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic Arizona

Scottsdale, Arizona, United States

Mayo Clinic in Jacksonville

Jacksonville, Florida, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RC0661

Identifier Type: OTHER

Identifier Source: secondary_id

06-002426

Identifier Type: OTHER

Identifier Source: secondary_id

RC0661

Identifier Type: -

Identifier Source: org_study_id