- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00436644
Lapatinib and Topotecan in Treating Patients With Ovarian Epithelial Cancer or Primary Peritoneal Cancer That Did Not Respond to Cisplatin or Carboplatin
A Phase II Trial of Lapatinib in Combination With Weekly Topotecan in Patients With Platinum-Refractory/Resistant Ovarian and Primary Peritoneal Carcinoma
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Arizona
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Scottsdale, Arizona, United States, 85254
- Mayo Clinic Arizona
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Florida
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Jacksonville, Florida, United States, 32224
- Mayo Clinic in Jacksonville
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Lapatinib + Topotecan
Assess biological effects of topotecan and lapatinib in patients with epithelial ovarian cancer and primary peritoneal carcinoma.
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1250 mg orally days 1 -28.
Other Names:
3.2 mg/m2 IV over 30 min in 100mL D5W (5% dextrose in water) or 0.9% NS at days 1, 8 & 15.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response Rate (Complete Response (CR) or Partial Response (PR))
Time Frame: Two consecutive evaluations at least 4 weeks apart
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Measurable disease patients: measureable disease is defined as at least one lesion whose longest diameter >= 2cm with conventional techniques or >=1cm with spiral CT
Non-measurable disease patients:
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Two consecutive evaluations at least 4 weeks apart
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Progression
Time Frame: Time from registration to progression (up to 2 years)
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Time to progression was defined as the number of months from registration to the date of disease progression, with patients who are progression free being censored on the date of their last evaluation.
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Time from registration to progression (up to 2 years)
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Adverse Event Profile
Time Frame: Every 4 weeks
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Number of patients that experienced adverse events (grade 3 or more) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v3.0
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Every 4 weeks
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Overall Survival
Time Frame: Time from Registration to Death or last follow-up (up to 3 years)
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Overall survival time was defined as the number of months from registration to the date of death or last follow-up
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Time from Registration to Death or last follow-up (up to 3 years)
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Paul Haluska, MD, PhD, Mayo Clinic
- Principal Investigator: John K. Camoriano, M.D., Mayo Clinic
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- RC0661 (Other Identifier: Mayo Clinic Cancer Center & MCCRC)
- P30CA015083 (U.S. NIH Grant/Contract)
- 06-002426 (Other Identifier: Mayo Clinic IRB)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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