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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00436644
First received: February 15, 2007
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Peritoneal Cavity Cancer
Drug: Lapatinib
Drug: Topotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Lapatinib in Combination With Weekly Topotecan in Patients With Platinum-Refractory/Resistant Ovarian and Primary Peritoneal Carcinoma

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Response Rate (Complete Response (CR) or Partial Response (PR)) [ Time Frame: Two consecutive evaluations at least 4 weeks apart ] [ Designated as safety issue: No ]

    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:
  • Time to Progression [ Time Frame: Time from registration to progression (up to 2 years) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]
    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 Frame: Time from Registration to Death or last follow-up (up to 3 years) ] [ Designated as safety issue: No ]
    Overall survival time was defined as the number of months from registration to the date of death or last follow-up


Enrollment: 18
Study Start Date: March 2007
Study Completion Date: November 2012
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lapatinib + Topotecan
Assess biological effects of topotecan and lapatinib in patients with epithelial ovarian cancer and primary peritoneal carcinoma.
Drug: Lapatinib
1250 mg orally days 1 -28.
Other Name: Tykerb
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.
Other Name: Hycamptin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00436644

Locations
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85254
United States, Florida
Mayo Clinic in Jacksonville
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Paul Haluska, MD, PhD Mayo Clinic
Principal Investigator: John K. Camoriano, M.D. Mayo Clinic
Principal Investigator: Candido E. Rivera, M.D. Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Paul Haluska, M.D., Ph.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00436644     History of Changes
Other Study ID Numbers: RC0661, P30CA015083, RC0661, 06-002426
Study First Received: February 15, 2007
Results First Received: February 17, 2012
Last Updated: March 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
recurrent ovarian epithelial cancer
peritoneal cavity cancer

Additional relevant MeSH terms:
Ovarian Neoplasms
Peritoneal Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Neoplasms by Histologic Type
Topotecan
Lapatinib
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014