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

Phase 2

Completed

• Conditions: Ovarian Cancer; Peritoneal Cavity Cancer
• Interventions: Drug: Lapatinib; Drug: Topotecan

• Registration Number: NCT00436644
• Lead Sponsor: Mayo Clinic

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.

Study Timeline

• Study First Submitted: 2007-02-15
• Study First Submitted QC: 2007-02-15
• Study First Posted: 2007-02-19
• Study Start: 2007-03
• Primary Completion: 2009-03
• Results First Submitted: 2012-02-17
• Results First Submitted QC: 2012-02-17
• Results First Posted: 2012-03-22
• Study Completion: 2012-11
• Status Verified: 2014-03
• Last Update Submitted: 2014-03-20
• Last Update Posted: 2014-04-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 18

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lapatinib + Topotecan	Lapatinib	Assess biological effects of topotecan and lapatinib in patients with epithelial ovarian cancer and primary peritoneal carcinoma.
Lapatinib + Topotecan	Topotecan	Assess biological effects of topotecan and lapatinib in patients with epithelial ovarian cancer and primary peritoneal carcinoma.

Primary Outcome Measures

Name	Time	Method
Response Rate (Complete Response (CR) or Partial Response (PR))	Two consecutive evaluations at least 4 weeks apart	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

Secondary Outcome Measures

Name	Time	Method
Time to Progression	Time from registration to progression (up to 2 years)	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.
Adverse Event Profile	Every 4 weeks	Number of patients that experienced adverse events (grade 3 or more) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v3.0
Overall Survival	Time from Registration to Death or last follow-up (up to 3 years)	Overall survival time was defined as the number of months from registration to the date of death or last follow-up

Trial Locations

Locations (3)

Mayo Clinic Cancer Center; 🇺🇸 Rochester, Minnesota, United States

Mayo Clinic Arizona; 🇺🇸 Scottsdale, Arizona, United States

Mayo Clinic in Jacksonville; 🇺🇸 Jacksonville, Florida, United States