Clinical trial NCT00113373: Lapatinib in Treating Patients With Persistent or Recurrent Ovarian Epithelial or Peritoneal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Peritoneal Cavity Cancer
Recurrent Ovarian Epithelial Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Gynecologic Oncology Group
First posted: 2005-06-08
Enrollment: 28
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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 (GOG) 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)
* Serum Glutamate Oxaloacetate Transaminase (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

Primary outcomes:
measure: Progression-free Survival (PFS) > 6 Months
timeFrame: For those patients whose disease can be evaluated by physical examination, progression was assessed prior to each 28-day cycle. CT scan or MRI if used to follow measurable disease every other cycle for the first 6 months
measure: Frequency and Severity of Adverse Effects as Assessed by Common Toxicity Criteria for Adverse Events (CTCAE) v3.0
timeFrame: Assessed every cycle while on treatment, 30 days after the last cycle of treatment
Secondary outcomes:
measure: Tumor Response
timeFrame: Baseline, every other cycle for 6 months and then every 6 months for up to 5 years
measure: Duration of Progression-free Survival
timeFrame: Every other cycle for 6 months and then every 6 months for up to 5 years.
measure: Overall Survival
timeFrame: From entry into the study to death or the date of last contact, assessed up to 5 years
measure: Prognostic Variable: Platinum Sensitivity
timeFrame: Baseline
measure: Prognostic Variables: Performance Status
timeFrame: Baseline
measure: Prognostic Variable: Cellular Histology
timeFrame: Baseline
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Gynecologic Oncology Group
state: Pennsylvania
Study officials:
affiliation: Gynecologic Oncology Group
name: Agustin Garcia
role: PRINCIPAL_INVESTIGATOR
References: