Lapatinib in Treating Patients With Persistent or Recurrent Ovarian Epithelial or Peritoneal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00113373
First received: June 7, 2005
Last updated: June 11, 2014
Last verified: December 2012
  Purpose

Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II trial is studying how well lapatinib works in treating patients with persistent or recurrent ovarian epithelial or peritoneal cancer.


Condition Intervention Phase
Primary Peritoneal Cavity Cancer
Recurrent Ovarian Epithelial Cancer
Drug: lapatinib ditosylate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of Lapatinib (GW572016) (NCI-Supplied Agent, NSC #727989) in the Treatment of Persistent or Recurrent Epithelial Ovarian or Primary Peritoneal Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    An analysis of any potential treatment effect on PFS or overall survival may be conducted against historical controls using a proportional hazards model that includes histological cell type, performance status, and platinum sensitivity.

  • Frequency and severity of adverse effects as assessed by CTCAE v3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Frequency of clinical response (partial and complete response) using RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Duration of progression-free survival [ Time Frame: From study entry until disease progression, death or date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
    An analysis of any potential treatment effect on PFS or overall survival may be conducted against historical controls using a proportional hazards model that includes histological cell type, performance status, and platinum sensitivity.

  • Duration of overall survival [ Time Frame: From entry into the study to death or the date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
    An analysis of any potential treatment effect on PFS or overall survival may be conducted against historical controls using a proportional hazards model that includes histological cell type, performance status, and platinum sensitivity.

  • Prognostic variables: platinum sensitivity, performance status, and cellular histology (clear cell or mucinous type) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    An analysis of any potential treatment effect on PFS or overall survival may be conducted against historical controls using a proportional hazards model that includes histological cell type, performance status, and platinum sensitivity.


Enrollment: 60
Study Start Date: May 2005
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (lapatinib ditosylate)
Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: lapatinib ditosylate
Given orally
Other Names:
  • GSK572016
  • GW-572016
  • GW2016
  • Lapatinib
  • Tykerb
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

OBJECTIVES: Primary I. Determine 6-month progression-free survival of patients with persistent or recurrent ovarian epithelial or primary peritoneal cancer treated with lapatinib.

II. Determine the nature and degree of toxicity of this drug in these patients.

Secondary I. Determine the clinical response rate (partial and complete response) in patients treated with this drug.

II. Determine the duration of progression-free and overall survival of patients treated with this drug.

III. Determine the impact of prognostic variables, including platinum sensitivity, performance status, and cellular histology (clear cell or mucinous type), on patients treated with this drug.

IV. Correlate tumor levels of expression of epidermal growth factor receptors (EGFR), phosphorylated EGFR, HER2/neu, and Ki-67, as determined by immunohistochemistry, with clinical response in patients treated with this drug.

V. Correlate EGFR mutations in tumor DNA with clinical response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 22-60 patients will be accrued for this study within 12-26 months.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed persistent or recurrent ovarian epithelial or primary peritoneal cancer
  • Measurable disease

    • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
    • Presence of ≥ 1 target lesion

      • Tumors within a previously irradiated field are not considered target lesions unless evidence of progression is documented or proven by biopsy 3 months after completion of radiotherapy
  • Disease progression during OR persistent disease after 1 prior platinum-based chemotherapy regimen* for primary disease containing carboplatin, cisplatin, or another organoplatinum compound

    • Initial treatment may have included high-dose therapy, consolidation therapy, or extended therapy administered after surgical or non-surgical assessment
    • Treatment-free interval after platinum-based chemotherapy < 12 months
  • Tumor accessible by guided core needle or fine needle biopsy
  • Ineligible for any higher priority Gynecologic Oncology Group protocols (i.e., any active phase III protocol for the same patient population)
  • Performance status - GOG 0-2 (patients who have received 1 prior treatment regimen)
  • Performance status - GOG 0-1 (patients who have received 2 prior treatment regimens)
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • SGOT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Creatinine ≤ 1.5 times ULN
  • Ejection fraction normal by echocardiogram or MUGA
  • No GI disease resulting in an inability to take oral medication
  • No malabsorption syndrome
  • No requirement for IV alimentation
  • No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 1 month after completion of study treatment
  • No active infection requiring antibiotics
  • No sensory or motor neuropathy > grade 1
  • No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
  • No history of allergic reaction attributed to compounds of similar chemical or biological composition to lapatinib
  • At least 4 weeks since prior immunologic agents for the malignancy
  • No prior trastuzumab (Herceptin®)or cetuximab
  • See Disease Characteristics
  • Recovered from prior chemotherapy
  • At least 6 weeks since prior nitrosoureas or mitomycin for the malignancy
  • No prior non-cytotoxic chemotherapy for recurrent or persistent disease
  • At least 2 weeks since prior and no concurrent dexamethasone or dexamethasone equivalent dose > 1.5 mg/day
  • At least 1 week since prior hormonal therapy for the malignancy
  • Concurrent hormone replacement therapy allowed
  • See Disease Characteristics
  • Recovered from prior radiotherapy
  • No prior radiotherapy to > 25% of marrow-bearing areas
  • See Disease Characteristics
  • Recovered from prior surgery
  • No prior surgical procedure affecting gastrointestinal (GI) absorption
  • At least 4 weeks since other prior therapy for the malignancy
  • At least 6 months since prior and no concurrent amiodarone
  • At least 1 week since other prior and no concurrent CYP3A4 inhibitors
  • At least 2 weeks since prior and no concurrent CYP3A4 inducers
  • At least 1 week since prior and no concurrent H2 inhibitors or proton pump inhibitors

    • Concurrent antacids allowed provided they are not administered within 1 hour before and 1 hour after study drug administration
  • No prior cancer treatment that would preclude study treatment
  • No prior lapatinib
  • No other prior target-specific therapy directed to the HER family (e.g., gefitinib or erlotinib)
  • No concurrent herbal medications
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00113373

Locations
United States, Pennsylvania
Gynecologic Oncology Group
Philadelphia, Pennsylvania, United States, 19103
Sponsors and Collaborators
Investigators
Principal Investigator: Agustin Garcia Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00113373     History of Changes
Other Study ID Numbers: NCI-2012-02654, NCI-2012-02654, CDR0000429548, GOG-0170G, GOG-0170G, U10CA027469
Study First Received: June 7, 2005
Last Updated: June 11, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 20, 2014