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

Phase 2
18 Years
Not Enrolling
Ovarian Cancer, Peritoneal Cavity Cancer

Thank you

Trial Information

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



- 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.


- 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.


- 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

- 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

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.

Inclusion Criteria


- 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


- 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


- 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

- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

Response Rate (Complete Response (CR) or Partial Response (PR))

Outcome Description:

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

Outcome Time Frame:

Two consecutive evaluations at least 4 weeks apart

Safety Issue:


Principal Investigator

Paul Haluska, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

March 2007

Completion Date:

March 2012

Related Keywords:

  • Ovarian Cancer
  • Peritoneal Cavity Cancer
  • recurrent ovarian epithelial cancer
  • peritoneal cavity cancer
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Neoplasms, Glandular and Epithelial



Mayo Clinic Cancer Center Rochester, Minnesota  55905
Mayo Clinic Arizona Scottsdale, Arizona  85259
Mayo Clinic in Jacksonville Jacksonville, Florida  32224