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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00436644
• Other study ID #: RC0661
• Secondary ID: P30CA015083RC066
• Status: Completed
• Phase: Phase 2
• First received: February 15, 2007
• Last updated: March 20, 2014
• Start date: March 2007
• Est. completion date: November 2012

Study information

• Verified date: March 2014
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: November 2012
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Peritoneal Cavity Cancer
• Peritoneal Neoplasms

Intervention

Drug:
• Lapatinib
1250 mg orally days 1 -28.
• 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.

Locations

Country	Name	City	State
United States	Mayo Clinic in Jacksonville	Jacksonville	Florida
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Mayo Clinic Arizona	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate (Complete Response (CR) or Partial Response (PR))	Measurable disease patients: measureable disease is defined as at least one lesion whose longest diameter >= 2cm with conventional techniques or >=1cm with spiral CT; Confirmed tumor response (complete and partial) as measured by RECIST(Response Evaluation Criteria In Solid Tumors) criteria on 2 consecutive evaluations at least 4 weeks apart.; Confirmed tumor response is at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions.; Non-measurable disease patients: Decrement in CA125 by > 50%; Improvement in other evaluable disease	Two consecutive evaluations at least 4 weeks apart	No
Secondary	Time to Progression	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.	Time from registration to progression (up to 2 years)	No
Secondary	Adverse Event Profile	Number of patients that experienced adverse events (grade 3 or more) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v3.0	Every 4 weeks	Yes
Secondary	Overall Survival	Overall survival time was defined as the number of months from registration to the date of death or last follow-up	Time from Registration to Death or last follow-up (up to 3 years)	No